Search

Your search keyword '"Hoover, Robert N"' showing total 37 results
Start Over Author "Hoover, Robert N" Topic female
37 results on '"Hoover, Robert N"'

1. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Author

Ahearn, Thomas U, Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L, Bolla, Manjeet K, Dennis, Joe, Dunning, Alison M, Lush, Michael, Wang, Qin, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J, Auer, Paul L, Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E, Bonanni, Bernardo, Børresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Brüning, Thomas, Burwinkel, Barbara, Buys, Saundra S, Canzian, Federico, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Chenevix-Trench, Georgia, Clarke, Christine L, Collée, J Margriet, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Devilee, Peter, Dörk, Thilo, Dwek, Miriam, Eccles, Diana M, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M, García-Sáenz, José A, Gaudet, Mia M, Giles, Graham G, Goldberg, Mark S, González-Neira, Anna, Alnæs, Grethe I Grenaker, Grip, Mervi, Guénel, Pascal, Haiman, Christopher A, Hall, Per, Hamann, Ute, Harkness, Elaine F, Heemskerk-Gerritsen, Bernadette AM, Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J, Hoover, Robert N, Hopper, John L, Howell, Anthony, Jakimovska, Milena, Jakubowska, Anna, John, Esther M, Jones, Michael E, Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M, Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N, Krüger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W, Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G, Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, and McLean, Catriona

Subjects
Human Genome, Cancer, Genetics, Clinical Research, Breast Cancer, 2.1 Biological and endogenous factors, Aetiology, Biomarkers, Tumor, Breast Neoplasms, Female, Genome-Wide Association Study, Humans, Receptor, ErbB-2, Receptors, Estrogen, Receptors, Progesterone, Risk, Breast cancer, Etiologic heterogeneity, Genetic predisposition, Common breast cancer susceptibility variants, NBCS Collaborators, ABCTB Investigators, kConFab/AOCS Investigators, Receptor, erbB-2, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate

Published
2022

2. Combined Associations of a Polygenic Risk Score and Classical Risk Factors With Breast Cancer Risk.

Author

Kapoor, Pooja Middha, Mavaddat, Nasim, Choudhury, Parichoy Pal, Wilcox, Amber N, Lindström, Sara, Behrens, Sabine, Michailidou, Kyriaki, Dennis, Joe, Bolla, Manjeet K, Wang, Qin, Jung, Audrey, Abu-Ful, Zomoroda, Ahearn, Thomas, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J, Auer, Paul L, Freeman, Laura E Beane, Becher, Heiko, Beckmann, Matthias W, Beeghly-Fadiel, Alicia, Benitez, Javier, Bernstein, Leslie, Bojesen, Stig E, Brauch, Hiltrud, Brenner, Hermann, Brüning, Thomas, Cai, Qiuyin, Campa, Daniele, Canzian, Federico, Carracedo, Angel, Carter, Brian D, Castelao, Jose E, Chanock, Stephen J, Chatterjee, Nilanjan, Chenevix-Trench, Georgia, Clarke, Christine L, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Dai, James Y, Earp, H Shelton, Ekici, Arif B, Eliassen, A Heather, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine, Fritschi, Lin, Gabrielson, Marike, Gago-Dominguez, Manuela, Gao, Chi, Gapstur, Susan M, Gaudet, Mia M, Giles, Graham G, González-Neira, Anna, Guénel, Pascal, Haeberle, Lothar, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hamann, Ute, Hatse, Sigrid, Heyworth, Jane, Holleczek, Bernd, Hoover, Robert N, Hopper, John L, Howell, Anthony, Hunter, David J, ABCTB Investigators, kConFab/AOCS Investigators, John, Esther M, Jones, Michael E, Kaaks, Rudolf, Keeman, Renske, Kitahara, Cari M, Ko, Yon-Dschun, Koutros, Stella, Kurian, Allison W, Lambrechts, Diether, Le Marchand, Loic, Lee, Eunjung, Lejbkowicz, Flavio, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, MacInnis, Robert J, Martinez, Maria Elena, Maurer, Tabea, McLean, Catriona, Neuhausen, Susan L, Newman, William G, Norman, Aaron, O'Brien, Katie M, Olshan, Andrew F, Olson, Janet E, Olsson, Håkan, and Orr, Nick

Subjects
ABCTB Investigators, kConFab/AOCS Investigators, Humans, Breast Neoplasms, Genetic Predisposition to Disease, Receptors, Estrogen, Medical History Taking, Body Mass Index, Logistic Models, Risk Factors, Case-Control Studies, Polymorphism, Single Nucleotide, Aged, Aged, 80 and over, Middle Aged, Female, White People, Aging, Breast Cancer, Prevention, Cancer, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.

Published
2021

3. Assessment of interactions between 205 breast cancer susceptibility loci and 13 established risk factors in relation to breast cancer risk, in the Breast Cancer Association Consortium

Author

Kapoor, Pooja Middha, Lindström, Sara, Behrens, Sabine, Wang, Xiaoliang, Michailidou, Kyriaki, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, Dunning, Alison M, Pharoah, Paul DP, Schmidt, Marjanka K, Kraft, Peter, García-Closas, Montserrat, Easton, Douglas F, Milne, Roger L, Chang-Claude, Jenny, Ahearn, Thomas, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J, Auer, Paul L, Augustinsson, Annelie, Freeman, Laura E Beane, Beckmann, Matthias W, Benitez, Javier, Bernstein, Leslie, Berrandou, Takiy, Bojesen, Stig E, Brauch, Hiltrud, Brenner, Hermann, Brock, Ian W, Broeks, Annegien, Brooks-Wilson, Angela, Butterbach, Katja, Cai, Qiuyin, Campa, Daniele, Canzian, Federico, Carter, Brian D, Castelao, Jose E, Chanock, Stephen J, Chenevix-Trench, Georgia, Cheng, Ting-Yuan David, Clarke, Christine L, Cordina-Duverger, Emilie, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Dai, James Y, Dite, Gillian S, Earp, H Shelton, Eliassen, A Heather, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine, Flyger, Henrik, Fritschi, Lin, Gabrielson, Marike, Gago-Dominguez, Manuela, Gapstur, Susan M, Gaudet, Mia M, Giles, Graham G, González-Neira, Anna, Grundy, Anne, Guénel, Pascal, Haeberle, Lothar, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hamann, Ute, Hankinson, Susan E, Harkness, Elaine F, Harstad, Tricia, He, Wei, Heyworth, Jane, Hoover, Robert N, Hopper, John L, Humphreys, Keith, Hunter, David J, Marrón, Pablo Isidro, John, Esther M, Jones, Michael E, Jung, Audrey, Kaaks, Rudolf, Keeman, Renske, Kitahara, Cari M, Ko, Yon-Dschun, Koutros, Stella, Krüger, Ute, Lambrechts, Diether, Le Marchand, Loic, Lee, Eunjung, Lejbkowicz, Flavio, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, and Makalic, Enes

Subjects
Genetics, Estrogen, Clinical Research, Cancer, Breast Cancer, Prevention, 2.1 Biological and endogenous factors, Aetiology, Alleles, Breast Neoplasms, Case-Control Studies, Europe, Factor XIII, Female, Gene-Environment Interaction, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Polymorphism, Single Nucleotide, Receptors, Estrogen, Risk Factors, White People, Breast Cancer Association Consortium, Europeans, Gene-environment interaction, breast cancer, epidemiology, risk factors, single nucleotide polymorphism, Statistics, Public Health and Health Services, Epidemiology
Abstract

BackgroundPrevious gene-environment interaction studies of breast cancer risk have provided sparse evidence of interactions. Using the largest available dataset to date, we performed a comprehensive assessment of potential effect modification of 205 common susceptibility variants by 13 established breast cancer risk factors, including replication of previously reported interactions.MethodsAnalyses were performed using 28 176 cases and 32 209 controls genotyped with iCOGS array and 44 109 cases and 48 145 controls genotyped using OncoArray from the Breast Cancer Association Consortium (BCAC). Gene-environment interactions were assessed using unconditional logistic regression and likelihood ratio tests for breast cancer risk overall and by estrogen-receptor (ER) status. Bayesian false discovery probability was used to assess the noteworthiness of the meta-analysed array-specific interactions.ResultsNoteworthy evidence of interaction at ≤1% prior probability was observed for three single nucleotide polymorphism (SNP)-risk factor pairs. SNP rs4442975 was associated with a greater reduction of risk of ER-positive breast cancer [odds ratio (OR)int = 0.85 (0.78-0.93), Pint = 2.8 x 10-4] and overall breast cancer [ORint = 0.85 (0.78-0.92), Pint = 7.4 x 10-5) in current users of estrogen-progesterone therapy compared with non-users. This finding was supported by replication using OncoArray data of the previously reported interaction between rs13387042 (r2 = 0.93 with rs4442975) and current estrogen-progesterone therapy for overall disease (Pint = 0.004). The two other interactions suggested stronger associations between SNP rs6596100 and ER-negative breast cancer with increasing parity and younger age at first birth.ConclusionsOverall, our study does not suggest strong effect modification of common breast cancer susceptibility variants by established risk factors.

Published
2020

4. Pubertal timing and breast density in young women: a prospective cohort study

Author

Houghton, Lauren C, Jung, Seungyoun, Troisi, Rebecca, LeBlanc, Erin S, Snetselaar, Linda G, Hylton, Nola M, Klifa, Catherine, Van Horn, Linda, Paris, Kenneth, Shepherd, John A, Hoover, Robert N, and Dorgan, Joanne F

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Breast Cancer, Cancer, Contraception/Reproduction, Clinical Research, Pediatric, Reproductive health and childbirth, Adolescent, Adult, Body Mass Index, Body Size, Breast, Breast Density, Breast Neoplasms, Child, Female, Humans, Magnetic Resonance Imaging, Menarche, Prospective Studies, Puberty, Risk Factors, Sexual Maturation, Time Factors, Breast cancer, Breast density, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BACKGROUND:Earlier age at onset of pubertal events and longer intervals between them (tempo) have been associated with increased breast cancer risk. It is unknown whether the timing and tempo of puberty are associated with adult breast density, which could mediate the increased risk. METHODS:From 1988 to 1997, girls participating in the Dietary Intervention Study in Children (DISC) were clinically assessed annually between ages 8 and 17 years for Tanner stages of breast development (thelarche) and pubic hair (pubarche), and onset of menses (menarche) was self-reported. In 2006-2008, 182 participants then aged 25-29 years had their percent dense breast volume (%DBV) measured by magnetic resonance imaging. Multivariable, linear mixed-effects regression models adjusted for reproductive factors, demographics, and body size were used to evaluate associations of age and tempo of puberty events with %DBV. RESULTS:The mean (standard deviation) and range of %DBV were 27.6 (20.5) and 0.2-86.1. Age at thelarche was negatively associated with %DBV (p trend = 0.04), while pubertal tempo between thelarche and menarche was positively associated with %DBV (p trend = 0.007). %DBV was 40% higher in women whose thelarche-to-menarche tempo was 2.9 years or longer (geometric mean (95%CI) = 21.8% (18.2-26.2%)) compared to women whose thelarche-to-menarche tempo was less than 1.6 years (geometric mean (95%CI) = 15.6% (13.9-17.5%)). CONCLUSIONS:Our results suggest that a slower pubertal tempo, i.e., greater number of months between thelarche and menarche, is associated with higher percent breast density in young women. Future research should examine whether breast density mediates the association between slower tempo and increased breast cancer risk.

Published
2019

5. Associations of obesity and circulating insulin and glucose with breast cancer risk: a Mendelian randomization analysis.

Author

Shu, Xiang, Wu, Lang, Khankari, Nikhil K, Shu, Xiao-Ou, Wang, Thomas J, Michailidou, Kyriaki, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, Milne, Roger L, Schmidt, Marjanka K, Pharoah, Paul DP, Andrulis, Irene L, Hunter, David J, Simard, Jacques, Easton, Douglas F, Zheng, Wei, Alicia, Beeghly-Fadiel J, Anton-Culver, Hoda, Antonenkova, Natalia N, Arndt, Volker, Aronson, Kristan J, Auer, Paul L, Barrdahl, Myrto, Baynes, Caroline, Beane Freeman, Laura E, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Stig E, Brauch, Hiltrud, Brenner, Hermann, Brinton, Louise, Broberg, Per, Brucker, Sara Y, Brüning, Thomas, Burwinkel, Barbara, Cai, Qiuyin, Caldés, Trinidad, Canzian, Federico, Carter, Brian D, Castelao, Jose E, Chang-Claude, Jenny, Chenevix-Trench, Georgia, David Cheng, Ting-Yuan, Clarke, Christine L, Conroy, Don M, Couch, Fergus J, Cox, David G, Cox, Angela, Cross, Simon S, Cunningham, Julie M, Czene, Kamila, Daly, Mary B, Doheny, Kimberly F, Dörk, Thilo, dos-Santos-Silva, Isabel, Dumont, Martine, Dunning, Alison M, Dwek, Miriam, Earp, H Shelton, Eccles, Diana M, Heather Eliassen, A, Engel, Christoph, Eriksson, Mikael, Gareth Evans, D, Fachal, Laura, Fasching, Peter A, Figueroa, Jonine, Fletcher, Olivia, Flyger, Henrik, Fritschi, Lin, Gabrielson, Marike, Gago-Dominguez, Manuela, Gapstur, Susan M, García-Closas, Montserrat, Gaudet, Mia M, Ghoussaini, Maya, Giles, Graham G, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Guénel, Pascal, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hallberg, Emily, Hamann, Ute, Harrington, Patricia, He, Wei, Hein, Alexander, Hicks, Belynda, Hillemanns, Peter, Hogervorst, Frans B, Hollestelle, Antoinette, and Hoover, Robert N

Subjects
Clinical Research, Diabetes, Prevention, Nutrition, Obesity, Cancer, Aging, Breast Cancer, Genetics, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Adult, Aged, Blood Glucose, Body Mass Index, Breast Neoplasms, Diabetes Mellitus, Type 2, Female, Humans, Insulin, Mendelian Randomization Analysis, Middle Aged, Obesity, Abdominal, Waist-Hip Ratio, Breast cancer, insulin, glucose, obesity, genetics, Mendelian randomization analysis, Breast Cancer Association Consortium, Statistics, Public Health and Health Services, Epidemiology
Abstract

BackgroundIn addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear.MethodsWe conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium.ResultsAll sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p  =  5.09  ×  10-4], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p  =  4.02  ×  10-4), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p  =  5.05  ×  10-19) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p  =  9.22  ×  10-6). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2-h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer.ConclusionsWe confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.

Published
2019

6. Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer.

Author

Ferreira, Manuel A, Gamazon, Eric R, Al-Ejeh, Fares, Aittomäki, Kristiina, Andrulis, Irene L, Anton-Culver, Hoda, Arason, Adalgeir, Arndt, Volker, Aronson, Kristan J, Arun, Banu K, Asseryanis, Ella, Azzollini, Jacopo, Balmaña, Judith, Barnes, Daniel R, Barrowdale, Daniel, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Białkowska, Katarzyna, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Stig E, Bolla, Manjeet K, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Broeks, Annegien, Burwinkel, Barbara, Caldés, Trinidad, Caligo, Maria A, Campa, Daniele, Campbell, Ian, Canzian, Federico, Carter, Jonathan, Carter, Brian D, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Christiansen, Hans, Chung, Wendy K, Claes, Kathleen BM, Clarke, Christine L, EMBRACE Collaborators, GC-HBOC Study Collaborators, GEMO Study Collaborators, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, de la Hoya, Miguel, Dennis, Joe, Devilee, Peter, Diez, Orland, Dörk, Thilo, Dunning, Alison M, Dwek, Miriam, Eccles, Diana M, Ejlertsen, Bent, Ellberg, Carolina, Engel, Christoph, Eriksson, Mikael, Fasching, Peter A, Fletcher, Olivia, Flyger, Henrik, Friedman, Eitan, Frost, Debra, Gabrielson, Marike, Gago-Dominguez, Manuela, Ganz, Patricia A, Gapstur, Susan M, Garber, Judy, García-Closas, Montserrat, García-Sáenz, José A, Gaudet, Mia M, Giles, Graham G, Glendon, Gord, Godwin, Andrew K, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Greene, Mark H, Gronwald, Jacek, Guénel, Pascal, Haiman, Christopher A, Hall, Per, Hamann, Ute, He, Wei, Heyworth, Jane, Hogervorst, Frans BL, Hollestelle, Antoinette, Hoover, Robert N, Hopper, John L, Hulick, Peter J, Humphreys, Keith, Imyanitov, Evgeny N, ABCTB Investigators, HEBON Investigators, and BCFR Investigators

Subjects
EMBRACE Collaborators, GC-HBOC Study Collaborators, GEMO Study Collaborators, ABCTB Investigators, HEBON Investigators, BCFR Investigators, Humans, Breast Neoplasms, Genetic Predisposition to Disease, Gene Expression Profiling, Quantitative Trait Loci, Female, Genome-Wide Association Study, Prevention, Cancer, Human Genome, Aging, Breast Cancer, Genetics, Biotechnology, 2.1 Biological and endogenous factors
Abstract

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.

Published
2019

7. A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer

Author

Wu, Lang, Shi, Wei, Long, Jirong, Guo, Xingyi, Michailidou, Kyriaki, Beesley, Jonathan, Bolla, Manjeet K, Shu, Xiao-Ou, Lu, Yingchang, Cai, Qiuyin, Al-Ejeh, Fares, Rozali, Esdy, Wang, Qin, Dennis, Joe, Li, Bingshan, Zeng, Chenjie, Feng, Helian, Gusev, Alexander, Barfield, Richard T, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J, Auer, Paul L, Barrdahl, Myrto, Baynes, Caroline, Beckmann, Matthias W, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Stig E, Brauch, Hiltrud, Brenner, Hermann, Brinton, Louise, Broberg, Per, Brucker, Sara Y, Burwinkel, Barbara, Caldés, Trinidad, Canzian, Federico, Carter, Brian D, Castelao, J Esteban, Chang-Claude, Jenny, Chen, Xiaoqing, Cheng, Ting-Yuan David, Christiansen, Hans, Clarke, Christine L, NBCS Collaborators, Collée, Margriet, Cornelissen, Sten, Couch, Fergus J, Cox, David, Cox, Angela, Cross, Simon S, Cunningham, Julie M, Czene, Kamila, Daly, Mary B, Devilee, Peter, Doheny, Kimberly F, Dörk, Thilo, dos-Santos-Silva, Isabel, Dumont, Martine, Dwek, Miriam, Eccles, Diana M, Eilber, Ursula, Eliassen, A Heather, Engel, Christoph, Eriksson, Mikael, Fachal, Laura, Fasching, Peter A, Figueroa, Jonine, Flesch-Janys, Dieter, Fletcher, Olivia, Flyger, Henrik, Fritschi, Lin, Gabrielson, Marike, Gago-Dominguez, Manuela, Gapstur, Susan M, García-Closas, Montserrat, Gaudet, Mia M, Ghoussaini, Maya, Giles, Graham G, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Guénel, Pascal, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hallberg, Emily, Hamann, Ute, Harrington, Patricia, Hein, Alexander, Hicks, Belynda, Hillemanns, Peter, Hollestelle, Antoinette, Hoover, Robert N, Hopper, John L, and Huang, Guanmengqian

Subjects
Biological Sciences, Genetics, Human Genome, Biotechnology, Prevention, Breast Cancer, Women's Health, Cancer Genomics, Cancer, 2.1 Biological and endogenous factors, Generic health relevance, Breast Neoplasms, Case-Control Studies, Female, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Risk, Transcriptome, NBCS Collaborators, kConFab/AOCS Investigators, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

The breast cancer risk variants identified in genome-wide association studies explain only a small fraction of the familial relative risk, and the genes responsible for these associations remain largely unknown. To identify novel risk loci and likely causal genes, we performed a transcriptome-wide association study evaluating associations of genetically predicted gene expression with breast cancer risk in 122,977 cases and 105,974 controls of European ancestry. We used data from the Genotype-Tissue Expression Project to establish genetic models to predict gene expression in breast tissue and evaluated model performance using data from The Cancer Genome Atlas. Of the 8,597 genes evaluated, significant associations were identified for 48 at a Bonferroni-corrected threshold of P

Published
2018

8. Association of Estrogen Metabolism with Breast Cancer Risk in Different Cohorts of Postmenopausal Women

Author

Sampson, Joshua N, Falk, Roni T, Schairer, Catherine, Moore, Steven C, Fuhrman, Barbara J, Dallal, Cher M, Bauer, Douglas C, Dorgan, Joanne F, Shu, Xiao-Ou, Zheng, Wei, Brinton, Louise A, Gail, Mitchell H, Ziegler, Regina G, Xu, Xia, Hoover, Robert N, and Gierach, Gretchen L

Subjects
Cancer, Breast Cancer, Prevention, Estrogen, Clinical Research, Aging, Adult, Aged, Breast Neoplasms, Chromatography, Liquid, Cohort Studies, Estrogens, Female, Humans, Hydroxylation, Middle Aged, Postmenopause, Risk, Tandem Mass Spectrometry, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Endogenous estradiol and estrone are linked causally to increased risks of breast cancer. In this study, we evaluated multiple competing hypotheses for how metabolism of these parent estrogens may influence risk. Prediagnostic concentrations of estradiol, estrone, and 13 metabolites were measured in 1,298 postmenopausal cases of breast cancer and 1,524 matched controls in four separate patient cohorts. The median time between sample collection and diagnosis was 4.4 to 12.7 years across the cohorts. Estrogen analytes were measured in serum or urine by liquid chromatography-tandem mass spectrometry. Total estrogen levels (summing all 15 estrogens/estrogen metabolites) were associated strongly and positively with breast cancer risk. Normalizing total estrogen levels, we also found that a relative increase in levels of 2-hydroxylation pathway metabolites, or in the ratio of 2-hydroxylation:16-hydroxylation pathway metabolites, were associated inversely with breast cancer risk. These associations varied by total estrogen levels, with the largest risk reductions occurring in women in the highest tertile. With appropriate validation, these findings suggest opportunities for breast cancer prevention by modifying individual estrogen metabolism profiles through either lifestyle alterations or chemopreventive strategies. Cancer Res; 77(4); 918-25. ©2017 AACR.

Published
2017

9. Opportunities—And Hard Work—Ahead

Author

Hoover, Robert N and Chanock, Stephen J

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Biomedical Research, Epigenomics, Gene Expression Profiling, Genetic Predisposition to Disease, Genomics, Humans, Metabolomics, Neoplasms, Proteomics, Signal Transduction, Transcriptome, Clinical Research, Human Genome, Brain Cancer, Genetics, Cancer, Brain Disorders, Neurosciences, Rare Diseases, Adult, Aged, Brain Neoplasms, Exome, Female, Germ-Line Mutation, Glioma, Male, Middle Aged, Oligodendroglioma, Pedigree, Shelterin Complex, Telomere-Binding Proteins, Gliogene Consortium, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

Gliomas are the most common brain tumor, with several histological subtypes of various malignancy grade. The genetic contribution to familial glioma is not well understood. Using whole exome sequencing of 90 individuals from 55 families, we identified two families with mutations in POT1 (p.G95C, p.E450X), a member of the telomere shelterin complex, shared by both affected individuals in each family and predicted to impact DNA binding and TPP1 binding, respectively. Validation in a separate cohort of 264 individuals from 246 families identified an additional mutation in POT1 (p.D617Efs), also predicted to disrupt TPP1 binding. All families with POT1 mutations had affected members with oligodendroglioma, a specific subtype of glioma more sensitive to irradiation. These findings are important for understanding the origin of glioma and could have importance for the future diagnostics and treatment of glioma.

Published
2014

10. Diabetes and risk of pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium

Author

Elena, Joanne W, Steplowski, Emily, Yu, Kai, Hartge, Patricia, Tobias, Geoffrey S, Brotzman, Michelle J, Chanock, Stephen J, Stolzenberg-Solomon, Rachael Z, Arslan, Alan A, Bueno-de-Mesquita, H Bas, Helzlsouer, Kathy, Jacobs, Eric J, LaCroix, Andrea, Petersen, Gloria, Zheng, Wei, Albanes, Demetrius, Allen, Naomi E, Amundadottir, Laufey, Bao, Ying, Boeing, Heiner, Boutron-Ruault, Marie-Christine, Buring, Julie E, Gaziano, J Michael, Giovannucci, Edward L, Duell, Eric J, Hallmans, Göran, Howard, Barbara V, Hunter, David J, Hutchinson, Amy, Jacobs, Kevin B, Kooperberg, Charles, Kraft, Peter, Mendelsohn, Julie B, Michaud, Dominique S, Palli, Domenico, Phillips, Lawrence S, Overvad, Kim, Patel, Alpa V, Sansbury, Leah, Shu, Xiao-Ou, Simon, Michael S, Slimani, Nadia, Trichopoulos, Dimitrios, Visvanathan, Kala, Virtamo, Jarmo, Wolpin, Brian M, Zeleniuch-Jacquotte, Anne, Fuchs, Charles S, Hoover, Robert N, and Gross, Myron

Subjects
Biomedical and Clinical Sciences, Epidemiology, Health Services and Systems, Health Sciences, Oncology and Carcinogenesis, Rare Diseases, Cancer, Pancreatic Cancer, Prevention, Digestive Diseases, Clinical Research, Diabetes, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Good Health and Well Being, Adenocarcinoma, Adult, Aged, Aged, 80 and over, Case-Control Studies, Cohort Studies, Diabetes Complications, Diabetes Mellitus, Female, Humans, Male, Middle Aged, Pancreatic Neoplasms, Risk Factors, Public Health and Health Services, Oncology and carcinogenesis
Abstract

PurposeDiabetes is a suspected risk factor for pancreatic cancer, but questions remain about whether it is a risk factor or a result of the disease. This study prospectively examined the association between diabetes and the risk of pancreatic adenocarcinoma in pooled data from the NCI pancreatic cancer cohort consortium (PanScan).MethodsThe pooled data included 1,621 pancreatic adenocarcinoma cases and 1,719 matched controls from twelve cohorts using a nested case-control study design. Subjects who were diagnosed with diabetes near the time (

Published
2013

11. A meta-analysis of genome-wide association studies of breast cancer identifies two novel susceptibility loci at 6q14 and 20q11

Author

Siddiq, Afshan, Couch, Fergus J, Chen, Gary K, Lindström, Sara, Eccles, Diana, Millikan, Robert C, Michailidou, Kyriaki, Stram, Daniel O, Beckmann, Lars, Rhie, Suhn Kyong, Ambrosone, Christine B, Aittomäki, Kristiina, Amiano, Pilar, Apicella, Carmel, Investigators, Australian Breast Cancer Tissue Bank, Baglietto, Laura, Bandera, Elisa V, Beckmann, Matthias W, Berg, Christine D, Bernstein, Leslie, Blomqvist, Carl, Brauch, Hiltrud, Brinton, Louise, Bui, Quang M, Buring, Julie E, Buys, Saundra S, Campa, Daniele, Carpenter, Jane E, Chasman, Daniel I, Chang-Claude, Jenny, Chen, Constance, Clavel-Chapelon, Françoise, Cox, Angela, Cross, Simon S, Czene, Kamila, Deming, Sandra L, Diasio, Robert B, Diver, W Ryan, Dunning, Alison M, Durcan, Lorraine, Ekici, Arif B, Fasching, Peter A, Study, Familial Breast Cancer, Feigelson, Heather Spencer, Fejerman, Laura, Figueroa, Jonine D, Fletcher, Olivia, Flesch-Janys, Dieter, Gaudet, Mia M, Consortium, The GENICA, Gerty, Susan M, Rodriguez-Gil, Jorge L, Giles, Graham G, van Gils, Carla H, Godwin, Andrew K, Graham, Nikki, Greco, Dario, Hall, Per, Hankinson, Susan E, Hartmann, Arndt, Hein, Rebecca, Heinz, Judith, Hoover, Robert N, Hopper, John L, Hu, Jennifer J, Huntsman, Scott, Ingles, Sue A, Irwanto, Astrid, Isaacs, Claudine, Jacobs, Kevin B, John, Esther M, Justenhoven, Christina, Kaaks, Rudolf, Kolonel, Laurence N, Coetzee, Gerhard A, Lathrop, Mark, Le Marchand, Loic, Lee, Adam M, Lee, I-Min, Lesnick, Timothy, Lichtner, Peter, Liu, Jianjun, Lund, Eiliv, Makalic, Enes, Martin, Nicholas G, McLean, Catriona A, Meijers-Heijboer, Hanne, Meindl, Alfons, Miron, Penelope, Monroe, Kristine R, Montgomery, Grant W, Müller-Myhsok, Bertram, Nickels, Stefan, Nyante, Sarah J, Olswold, Curtis, Overvad, Kim, Palli, Domenico, Park, Daniel J, Palmer, Julie R, and Pathak, Harsh

Subjects
Biological Sciences, Genetics, Clinical Research, Aging, Human Genome, Breast Cancer, Cancer, Aetiology, 2.1 Biological and endogenous factors, Breast Neoplasms, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Receptors, Estrogen, Australian Breast Cancer Tissue Bank Investigators, Familial Breast Cancer Study, GENICA Consortium, Medical and Health Sciences, Genetics & Heredity
Abstract

Genome-wide association studies (GWAS) of breast cancer defined by hormone receptor status have revealed loci contributing to susceptibility of estrogen receptor (ER)-negative subtypes. To identify additional genetic variants for ER-negative breast cancer, we conducted the largest meta-analysis of ER-negative disease to date, comprising 4754 ER-negative cases and 31 663 controls from three GWAS: NCI Breast and Prostate Cancer Cohort Consortium (BPC3) (2188 ER-negative cases; 25 519 controls of European ancestry), Triple Negative Breast Cancer Consortium (TNBCC) (1562 triple negative cases; 3399 controls of European ancestry) and African American Breast Cancer Consortium (AABC) (1004 ER-negative cases; 2745 controls). We performed in silico replication of 86 SNPs at P ≤ 1 × 10(-5) in an additional 11 209 breast cancer cases (946 with ER-negative disease) and 16 057 controls of Japanese, Latino and European ancestry. We identified two novel loci for breast cancer at 20q11 and 6q14. SNP rs2284378 at 20q11 was associated with ER-negative breast cancer (combined two-stage OR = 1.16; P = 1.1 × 10(-8)) but showed a weaker association with overall breast cancer (OR = 1.08, P = 1.3 × 10(-6)) based on 17 869 cases and 43 745 controls and no association with ER-positive disease (OR = 1.01, P = 0.67) based on 9965 cases and 22 902 controls. Similarly, rs17530068 at 6q14 was associated with breast cancer (OR = 1.12; P = 1.1 × 10(-9)), and with both ER-positive (OR = 1.09; P = 1.5 × 10(-5)) and ER-negative (OR = 1.16, P = 2.5 × 10(-7)) disease. We also confirmed three known loci associated with ER-negative (19p13) and both ER-negative and ER-positive breast cancer (6q25 and 12p11). Our results highlight the value of large-scale collaborative studies to identify novel breast cancer risk loci.

Published
2012

12. Genome-wide association study of glioma and meta-analysis

Author

Rajaraman, Preetha, Melin, Beatrice S, Wang, Zhaoming, McKean-Cowdin, Roberta, Michaud, Dominique S, Wang, Sophia S, Bondy, Melissa, Houlston, Richard, Jenkins, Robert B, Wrensch, Margaret, Yeager, Meredith, Ahlbom, Anders, Albanes, Demetrius, Andersson, Ulrika, Freeman, Laura E Beane, Buring, Julie E, Butler, Mary Ann, Braganza, Melissa, Carreon, Tania, Feychting, Maria, Fleming, Sarah J, Gapstur, Susan M, Gaziano, J Michael, Giles, Graham G, Hallmans, Goran, Henriksson, Roger, Hoffman-Bolton, Judith, Inskip, Peter D, Johansen, Christoffer, Kitahara, Cari M, Lathrop, Mark, Liu, Chenwei, Le Marchand, Loic, Linet, Martha S, Lonn, Stefan, Peters, Ulrike, Purdue, Mark P, Rothman, Nathaniel, Ruder, Avima M, Sanson, Marc, Sesso, Howard D, Severi, Gianluca, Shu, Xiao-Ou, Simon, Matthias, Stampfer, Meir, Stevens, Victoria L, Visvanathan, Kala, White, Emily, Wolk, Alicja, Zeleniuch-Jacquotte, Anne, Zheng, Wei, Decker, Paul, Enciso-Mora, Victor, Fridley, Brooke, Gao, Yu-Tang, Kosel, Matthew, Lachance, Daniel H, Lau, Ching, Rice, Terri, Swerdlow, Anthony, Wiemels, Joseph L, Wiencke, John K, Shete, Sanjay, Xiang, Yong-Bing, Xiao, Yuanyuan, Hoover, Robert N, Fraumeni, Joseph F, Chatterjee, Nilanjan, Hartge, Patricia, and Chanock, Stephen J

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Clinical Research, Brain Disorders, Prevention, Brain Cancer, Neurosciences, Cancer, Human Genome, Rare Diseases, Aetiology, 2.1 Biological and endogenous factors, Aged, Brain Neoplasms, Case-Control Studies, Cohort Studies, Cyclin-Dependent Kinase Inhibitor p15, DNA Helicases, Female, Genome-Wide Association Study, Glioblastoma, Glioma, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Telomerase, Complementary and Alternative Medicine, Paediatrics and Reproductive Medicine, Genetics & Heredity, Reproductive medicine
Abstract

Gliomas account for approximately 80 % of all primary malignant brain tumors and, despite improvements in clinical care over the last 20 years, remain among the most lethal tumors, underscoring the need for gaining new insights that could translate into clinical advances. Recent genome-wide association studies (GWAS) have identified seven new susceptibility regions. We conducted a new independent GWAS of glioma using 1,856 cases and 4,955 controls (from 14 cohort studies, 3 case-control studies, and 1 population-based case-only study) and found evidence of strong replication for three of the seven previously reported associations at 20q13.33 (RTEL), 5p15.33 (TERT), and 9p21.3 (CDKN2BAS), and consistent association signals for the remaining four at 7p11.2 (EGFR both loci), 8q24.21 (CCDC26) and 11q23.3 (PHLDB1). The direction and magnitude of the signal were consistent for samples from cohort and case-control studies, but the strength of the association was more pronounced for loci rs6010620 (20q,13.33; RTEL) and rs2736100 (5p15.33, TERT) in cohort studies despite the smaller number of cases in this group, likely due to relatively more higher grade tumors being captured in the cohort studies. We further examined the 85 most promising single nucleotide polymorphism (SNP) markers identified in our study in three replication sets (5,015 cases and 11,601 controls), but no new markers reached genome-wide significance. Our findings suggest that larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk.

Published
2012

13. Alcohol intake and pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium (PanScan)

Author

Michaud, Dominique S, Vrieling, Alina, Jiao, Li, Mendelsohn, Julie B, Steplowski, Emily, Lynch, Shannon M, Wactawski-Wende, Jean, Arslan, Alan A, Bas Bueno-de-Mesquita, H, Fuchs, Charles S, Gross, Myron, Helzlsouer, Kathy, Jacobs, Eric J, LaCroix, Andrea, Petersen, Gloria, Zheng, Wei, Allen, Naomi, Ammundadottir, Laufey, Bergmann, Manuela M, Boffetta, Paolo, Buring, Julie E, Canzian, Federico, Chanock, Stephen J, Clavel-Chapelon, Françoise, Clipp, Sandra, Freiberg, Matthew S, Michael Gaziano, J, Giovannucci, Edward L, Hankinson, Susan, Hartge, Patricia, Hoover, Robert N, Allan Hubbell, F, Hunter, David J, Hutchinson, Amy, Jacobs, Kevin, Kooperberg, Charles, Kraft, Peter, Manjer, Jonas, Navarro, Carmen, Peeters, Petra HM, Shu, Xiao-Ou, Stevens, Victoria, Thomas, Gilles, Tjønneland, Anne, Tobias, Geoffrey S, Trichopoulos, Dimitrios, Tumino, Rosario, Vineis, Paolo, Virtamo, Jarmo, Wallace, Robert, Wolpin, Brian M, Yu, Kai, Zeleniuch-Jacquotte, Anne, and Stolzenberg-Solomon, Rachael Z

Subjects
Health Services and Systems, Biomedical and Clinical Sciences, Health Sciences, Alcoholism, Alcohol Use and Health, Cancer, Digestive Diseases, Pancreatic Cancer, Rare Diseases, Clinical Research, Substance Misuse, Oral and gastrointestinal, Good Health and Well Being, Aged, Alcohol Drinking, Case-Control Studies, Cohort Studies, Female, Humans, Male, Pancreatic Neoplasms, Prospective Studies, Alcohol, Pancreatic cancer, Pooled analysis, Oncology and Carcinogenesis, Public Health and Health Services, Epidemiology, Oncology and carcinogenesis
Abstract

The literature has consistently reported no association between low to moderate alcohol consumption and pancreatic cancer; however, a few studies have shown that high levels of intake may increase risk. Most single studies have limited power to detect associations even in the highest alcohol intake categories or to examine associations by alcohol type. We analyzed these associations using 1,530 pancreatic cancer cases and 1,530 controls from the Pancreatic Cancer Cohort Consortium (PanScan) nested case-control study. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression, adjusting for potential confounders. We observed no significant overall association between total alcohol (ethanol) intake and pancreatic cancer risk (OR = 1.38, 95% CI = 0.86-2.23, for 60 or more g/day vs. >0 to

Published
2010

14. Anthropometric Measures, Body Mass Index, and Pancreatic Cancer: A Pooled Analysis From the Pancreatic Cancer Cohort Consortium (PanScan)

Author

Arslan, Alan A, Helzlsouer, Kathy J, Kooperberg, Charles, Shu, Xiao-Ou, Steplowski, Emily, Bueno-de-Mesquita, H Bas, Fuchs, Charles S, Gross, Myron D, Jacobs, Eric J, Lacroix, Andrea Z, Petersen, Gloria M, Stolzenberg-Solomon, Rachael Z, Zheng, Wei, Albanes, Demetrius, Amundadottir, Laufey, Bamlet, William R, Barricarte, Aurelio, Bingham, Sheila A, Boeing, Heiner, Boutron-Ruault, Marie-Christine, Buring, Julie E, Chanock, Stephen J, Clipp, Sandra, Gaziano, J Michael, Giovannucci, Edward L, Hankinson, Susan E, Hartge, Patricia, Hoover, Robert N, Hunter, David J, Hutchinson, Amy, Jacobs, Kevin B, Kraft, Peter, Lynch, Shannon M, Manjer, Jonas, Manson, Joann E, McTiernan, Anne, McWilliams, Robert R, Mendelsohn, Julie B, Michaud, Dominique S, Palli, Domenico, Rohan, Thomas E, Slimani, Nadia, Thomas, Gilles, Tjønneland, Anne, Tobias, Geoffrey S, Trichopoulos, Dimitrios, Virtamo, Jarmo, Wolpin, Brian M, Yu, Kai, Zeleniuch-Jacquotte, Anne, and Patel, Alpa V

Subjects
Obesity, Cancer, Clinical Research, Nutrition, Prevention, Pancreatic Cancer, Rare Diseases, Digestive Diseases, Adult, Aged, Aged, 80 and over, Body Mass Index, Case-Control Studies, Female, Humans, Logistic Models, Male, Middle Aged, Overweight, Pancreatic Neoplasms, Risk Factors, Sex Distribution, United States, Waist Circumference, Pancreatic Cancer Cohort Consortium, Clinical Sciences, Opthalmology and Optometry, Public Health and Health Services
Abstract

BackgroundObesity has been proposed as a risk factor for pancreatic cancer.MethodsPooled data were analyzed from the National Cancer Institute Pancreatic Cancer Cohort Consortium (PanScan) to study the association between prediagnostic anthropometric measures and risk of pancreatic cancer. PanScan applied a nested case-control study design and included 2170 cases and 2209 control subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression for cohort-specific quartiles of body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]), weight, height, waist circumference, and waist to hip ratio as well as conventional BMI categories (underweight, or = 35.0). Models were adjusted for potential confounders.ResultsIn all of the participants, a positive association between increasing BMI and risk of pancreatic cancer was observed (adjusted OR for the highest vs lowest BMI quartile, 1.33; 95% CI, 1.12-1.58; P(trend) < .001). In men, the adjusted OR for pancreatic cancer for the highest vs lowest quartile of BMI was 1.33 (95% CI, 1.04-1.69; P(trend) < .03), and in women it was 1.34 (95% CI, 1.05-1.70; P(trend) = .01). Increased waist to hip ratio was associated with increased risk of pancreatic cancer in women (adjusted OR for the highest vs lowest quartile, 1.87; 95% CI, 1.31-2.69; P(trend) = .003) but less so in men.ConclusionsThese findings provide strong support for a positive association between BMI and pancreatic cancer risk. In addition, centralized fat distribution may increase pancreatic cancer risk, especially in women.

Published
2010

15. Pancreatic cancer risk and ABO blood group alleles: results from the pancreatic cancer cohort consortium.

Author

Wolpin, Brian M, Kraft, Peter, Gross, Myron, Helzlsouer, Kathy, Bueno-de-Mesquita, H Bas, Steplowski, Emily, Stolzenberg-Solomon, Rachael Z, Arslan, Alan A, Jacobs, Eric J, Lacroix, Andrea, Petersen, Gloria, Zheng, Wei, Albanes, Demetrius, Allen, Naomi E, Amundadottir, Laufey, Anderson, Garnet, Boutron-Ruault, Marie-Christine, Buring, Julie E, Canzian, Federico, Chanock, Stephen J, Clipp, Sandra, Gaziano, John Michael, Giovannucci, Edward L, Hallmans, Göran, Hankinson, Susan E, Hoover, Robert N, Hunter, David J, Hutchinson, Amy, Jacobs, Kevin, Kooperberg, Charles, Lynch, Shannon M, Mendelsohn, Julie B, Michaud, Dominique S, Overvad, Kim, Patel, Alpa V, Rajkovic, Aleksandar, Sanchéz, Maria-José, Shu, Xiao-Ou, Slimani, Nadia, Thomas, Gilles, Tobias, Geoffrey S, Trichopoulos, Dimitrios, Vineis, Paolo, Virtamo, Jarmo, Wactawski-Wende, Jean, Yu, Kai, Zeleniuch-Jacquotte, Anne, Hartge, Patricia, and Fuchs, Charles S

Subjects
Humans, Pancreatic Neoplasms, Genetic Predisposition to Disease, ABO Blood-Group System, Logistic Models, Odds Ratio, Risk Factors, Cohort Studies, Gene Frequency, Genotype, Alleles, Aged, Middle Aged, Female, Male, Clinical Research, Genetics, Pancreatic Cancer, Rare Diseases, Digestive Diseases, Cancer, Prevention, 2.1 Biological and endogenous factors, Oncology & Carcinogenesis, Oncology and Carcinogenesis
Abstract

A recent genome-wide association study (PanScan) identified significant associations at the ABO gene locus with risk of pancreatic cancer, but the influence of specific ABO genotypes remains unknown. We determined ABO genotypes (OO, AO, AA, AB, BO, and BB) in 1,534 cases and 1,583 controls from 12 prospective cohorts in PanScan, grouping participants by genotype-derived serologic blood type (O, A, AB, and B). Adjusted odds ratios (ORs) for pancreatic cancer by ABO alleles were calculated using logistic regression. Compared with blood type O, the ORs for pancreatic cancer in subjects with types A, AB, and B were 1.38 [95% confidence interval (95% CI), 1.18-1.62], 1.47 (95% CI, 1.07-2.02), and 1.53 (95% CI, 1.21-1.92), respectively. The incidence rates for blood types O, A, AB, and B were 28.9, 39.9, 41.8, and 44.5 cases per 100,000 subjects per year. An increase in risk was noted with the addition of each non-O allele. Compared with OO genotype, subjects with AO and AA genotype had ORs of 1.33 (95% CI, 1.13-1.58) and 1.61 (95% CI, 1.22-2.18), whereas subjects with BO and BB genotypes had ORs of 1.45 (95% CI, 1.14-1.85) and 2.42 (1.28-4.57). The population attributable fraction for non-O blood type was 19.5%. In a joint model with smoking, current smokers with non-O blood type had an adjusted OR of 2.68 (95% CI, 2.03-3.54) compared with nonsmokers of blood type O. We concluded that ABO genotypes were significantly associated with pancreatic cancer risk.

Published
2010

16. Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer.

Author

Amundadottir, Laufey, Kraft, Peter, Stolzenberg-Solomon, Rachael Z, Fuchs, Charles S, Petersen, Gloria M, Arslan, Alan A, Bueno-de-Mesquita, H Bas, Gross, Myron, Helzlsouer, Kathy, Jacobs, Eric J, LaCroix, Andrea, Zheng, Wei, Albanes, Demetrius, Bamlet, William, Berg, Christine D, Berrino, Franco, Bingham, Sheila, Buring, Julie E, Bracci, Paige M, Canzian, Federico, Clavel-Chapelon, Françoise, Clipp, Sandra, Cotterchio, Michelle, de Andrade, Mariza, Duell, Eric J, Fox, John W, Gallinger, Steven, Gaziano, J Michael, Giovannucci, Edward L, Goggins, Michael, González, Carlos A, Hallmans, Göran, Hankinson, Susan E, Hassan, Manal, Holly, Elizabeth A, Hunter, David J, Hutchinson, Amy, Jackson, Rebecca, Jacobs, Kevin B, Jenab, Mazda, Kaaks, Rudolf, Klein, Alison P, Kooperberg, Charles, Kurtz, Robert C, Li, Donghui, Lynch, Shannon M, Mandelson, Margaret, McWilliams, Robert R, Mendelsohn, Julie B, Michaud, Dominique S, Olson, Sara H, Overvad, Kim, Patel, Alpa V, Peeters, Petra HM, Rajkovic, Aleksandar, Riboli, Elio, Risch, Harvey A, Shu, Xiao-Ou, Thomas, Gilles, Tobias, Geoffrey S, Trichopoulos, Dimitrios, Van Den Eeden, Stephen K, Virtamo, Jarmo, Wactawski-Wende, Jean, Wolpin, Brian M, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Chanock, Stephen J, Hartge, Patricia, and Hoover, Robert N

Subjects
Chromosomes, Human, Pair 9, Humans, Pancreatic Neoplasms, Genetic Predisposition to Disease, ABO Blood-Group System, Logistic Models, Odds Ratio, Risk Factors, Case-Control Studies, Cohort Studies, Prospective Studies, Gene Frequency, Genotype, Haplotypes, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Alleles, Introns, United States, Female, Male, Genetic Variation, Genome-Wide Association Study, Prevention, Rare Diseases, Cancer, Genetics, Clinical Research, Pancreatic Cancer, Digestive Diseases, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 x 10(-8); multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B.

Published
2009

17. Cigarette Smoking and Pancreatic Cancer: A Pooled Analysis From the Pancreatic Cancer Cohort Consortium

Author

Lynch, Shannon M, Vrieling, Alina, Lubin, Jay H, Kraft, Peter, Mendelsohn, Julie B, Hartge, Patricia, Canzian, Federico, Steplowski, Emily, Arslan, Alan A, Gross, Myron, Helzlsouer, Kathy, Jacobs, Eric J, LaCroix, Andrea, Petersen, Gloria, Zheng, Wei, Albanes, Demetrius, Amundadottir, Laufey, Bingham, Sheila A, Boffetta, Paolo, Boutron-Ruault, Marie-Christine, Chanock, Stephen J, Clipp, Sandra, Hoover, Robert N, Jacobs, Kevin, Johnson, Karen C, Kooperberg, Charles, Luo, Juhua, Messina, Catherine, Palli, Domenico, Patel, Alpa V, Riboli, Elio, Shu, Xiao-Ou, Rodriguez Suarez, Laudina, Thomas, Gilles, Tjønneland, Anne, Tobias, Geoffrey S, Tong, Elissa, Trichopoulos, Dimitrios, Virtamo, Jarmo, Ye, Weimin, Yu, Kai, Zeleniuch-Jacquette, Anne, Bueno-de-Mesquita, H Bas, and Stolzenberg-Solomon, Rachael Z

Subjects
Tobacco, Digestive Diseases, Cancer, Pancreatic Cancer, Rare Diseases, Prevention, Tobacco Smoke and Health, Prevention of disease and conditions, and promotion of well-being, 3.1 Primary prevention interventions to modify behaviours or promote wellbeing, Adenocarcinoma, Adult, Aged, Aged, 80 and over, Case-Control Studies, Cohort Studies, Female, Humans, Male, Middle Aged, Pancreatic Neoplasms, Prospective Studies, Risk, Smoking, Smoking Cessation, United States, pancreas, pancreatic neoplasms, smoking, tobacco use cessation, Mathematical Sciences, Medical and Health Sciences, Epidemiology
Abstract

Smoking is an established risk factor for pancreatic cancer; however, detailed examination of the association of smoking intensity, smoking duration, and cumulative smoking dose with pancreatic cancer is limited. The authors analyzed pooled data from the international Pancreatic Cancer Cohort Consortium nested case-control study (1,481 cases, 1,539 controls). Odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression. Smoking intensity effects were examined with an excess odds ratio model that was linear in pack-years and exponential in cigarettes smoked per day and its square. When compared with never smokers, current smokers had a significantly elevated risk (odds ratio (OR) = 1.77, 95% confidence interval (CI): 1.38, 2.26). Risk increased significantly with greater intensity (> or =30 cigarettes/day: OR = 1.75, 95% CI: 1.27, 2.42), duration (> or =50 years: OR = 2.13, 95% CI: 1.25, 3.62), and cumulative smoking dose (> or =40 pack-years: OR = 1.78, 95% CI: 1.35, 2.34). Risk more than 15 years after smoking cessation was similar to that for never smokers. Estimates of excess odds ratio per pack-year declined with increasing intensity, suggesting greater risk for total exposure delivered at lower intensity for longer duration than for higher intensity for shorter duration. This finding and the decline in risk after smoking cessation suggest that smoking has a late-stage effect on pancreatic carcinogenesis.

Published
2009

18. Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses

Author

Zhang, Haoyu, Ahearn, Thomas U, Lecarpentier, Julie, Barnes, Daniel, Beesley, Jonathan, Qi, Guanghao, Jiang, Xia, O'Mara, Tracy A, Zhao, Ni, Bolla, Manjeet K, Dunning, Alison M, Dennis, Joe, Wang, Qin, Ful, Zumuruda Abu, Aittomäki, Kristiina, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J, Arun, Banu K, Auer, Paul L, Azzollini, Jacopo, Barrowdale, Daniel, Becher, Heiko, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bialkowska, Katarzyna, Blanco, Ana, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Stig E, Bonanni, Bernardo, Bondavalli, Davide, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Broeks, Annegien, Brucker, Sara Y, Brüning, Thomas, Burwinkel, Barbara, Buys, Saundra S, Byers, Helen, Caldés, Trinidad, Caligo, Maria A, Calvello, Mariarosaria, Campa, Daniele, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Christiaens, Melissa, Christiansen, Hans, Chung, Wendy K, Claes, Kathleen BM, Clarke, Christine L, Cornelissen, Sten, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Devilee, Peter, Diez, Orland, Domchek, Susan M, Dörk, Thilo, Dwek, Miriam, Eccles, Diana M, Ekici, Arif B, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine, Foretova, Lenka, Fostira, Florentia, Friedman, Eitan, Frost, Debra, Gago-Dominguez, Manuela, Gapstur, Susan M, Garber, Judy, García-Sáenz, José A, Gaudet, Mia M, Gayther, Simon A, Giles, Graham G, Godwin, Andrew K, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Greene, Mark H, Gronwald, Jacek, Guénel, Pascal, Häberle, Lothar, Hahnen, Eric, Haiman, Christopher A, Hake, Christopher R, Hall, Per, Hamann, Ute, Harkness, Elaine F, Heemskerk-Gerritsen, Bernadette AM, Hillemanns, Peter, Hogervorst, Frans BL, Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J, Hoover, Robert N, Hopper, John L, Howell, Anthony, Huebner, Hanna, Hulick, Peter J, Imyanitov, Evgeny N, kConFab Investigators, ABCTB Investigators, Isaacs, Claudine, Izatt, Louise, Jager, Agnes, Jakimovska, Milena, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Janni, Wolfgang, John, Esther M, Jones, Michael E, Jung, Audrey, Kaaks, Rudolf, Kapoor, Pooja Middha, Karlan, Beth Y, Keeman, Renske, Khan, Sofia, Khusnutdinova, Elza, Kitahara, Cari M, Ko, Yon-Dschun, Konstantopoulou, Irene, Koppert, Linetta B, Koutros, Stella, Kristensen, Vessela N, Laenkholm, Anne-Vibeke, Lambrechts, Diether, Larsson, Susanna C, Laurent-Puig, Pierre, Lazaro, Conxi, Lazarova, Emilija, Lejbkowicz, Flavio, Leslie, Goska, Lesueur, Fabienne, Lindblom, Annika, Lissowska, Jolanta, Lo, Wing-Yee, Loud, Jennifer T, Lubinski, Jan, Lukomska, Alicja, MacInnis, Robert J, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Matricardi, Laura, McGuffog, Lesley, McLean, Catriona, Mebirouk, Noura, Meindl, Alfons, Menon, Usha, Miller, Austin, Mingazheva, Elvira, Montagna, Marco, Mulligan, Anna Marie, Mulot, Claire, Muranen, Taru A, Nathanson, Katherine L, Neuhausen, Susan L, Nevanlinna, Heli, Neven, Patrick, Newman, William G, Nielsen, Finn C, Nikitina-Zake, Liene, Nodora, Jesse, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I, Olsson, Håkan, Orr, Nick, Papi, Laura, Papp, Janos, Park-Simon, Tjoung-Won, Parsons, Michael T, Peissel, Bernard, Peixoto, Ana, Peshkin, Beth, Peterlongo, Paolo, Peto, Julian, Phillips, Kelly-Anne, Piedmonte, Marion, Plaseska-Karanfilska, Dijana, Prajzendanc, Karolina, Prentice, Ross, Prokofyeva, Darya, Rack, Brigitte, Radice, Paolo, Ramus, Susan J, Rantala, Johanna, Rashid, Muhammad U, Rennert, Gad, Rennert, Hedy S, Risch, Harvey A, Romero, Atocha, Rookus, Matti A, Rübner, Matthias, Rüdiger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P, Sawyer, Elinor J, Scheuner, Maren T, Schmutzler, Rita K, Schneeweiss, Andreas, Schoemaker, Minouk J, Schöttker, Ben, Schürmann, Peter, Senter, Leigha, Sharma, Priyanka, Sherman, Mark E, Shu, Xiao-Ou, Singer, Christian F, Smichkoska, Snezhana, Soucy, Penny, Southey, Melissa C, Spinelli, John J, Stone, Jennifer, Stoppa-Lyonnet, Dominique, EMBRACE Study, GEMO Study Collaborators, Swerdlow, Anthony J, Szabo, Csilla I, Tamimi, Rulla M, Tapper, William J, Taylor, Jack A, Teixeira, Manuel R, Terry, MaryBeth, Thomassen, Mads, Thull, Darcy L, Tischkowitz, Marc, Toland, Amanda E, Tollenaar, Rob AEM, Tomlinson, Ian, Torres, Diana, Troester, Melissa A, Truong, Thérèse, Tung, Nadine, Untch, Michael, Vachon, Celine M, van den Ouweland, Ans MW, van der Kolk, Lizet E, van Veen, Elke M, vanRensburg, Elizabeth J, Vega, Ana, Wappenschmidt, Barbara, Weinberg, Clarice R, Weitzel, Jeffrey N, Wildiers, Hans, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R, Yannoukakos, Drakoulis, Zheng, Wei, Zorn, Kristin K, Milne, Roger L, Kraft, Peter, Simard, Jacques, Pharoah, Paul DP, Michailidou, Kyriaki, Antoniou, Antonis C, Schmidt, Marjanka K, Chenevix-Trench, Georgia, Easton, Douglas F, Chatterjee, Nilanjan, García-Closas, Montserrat, Barnes, Daniel [0000-0002-3781-7570], O'Mara, Tracy A [0000-0002-5436-3232], Dunning, Alison M [0000-0001-6651-7166], Dennis, Joe [0000-0003-4591-1214], Andrulis, Irene L [0000-0002-4226-6435], Arndt, Volker [0000-0001-9320-8684], Azzollini, Jacopo [0000-0002-9364-9778], Bojesen, Stig E [0000-0002-4061-4133], Bonanni, Bernardo [0000-0003-3589-2128], Brauch, Hiltrud [0000-0001-7531-2736], Caldés, Trinidad [0000-0002-1038-5392], Calvello, Mariarosaria [0000-0003-2113-8503], Chanock, Stephen J [0000-0002-2324-3393], Claes, Kathleen BM [0000-0003-0841-7372], Devilee, Peter [0000-0002-8023-2009], Dörk, Thilo [0000-0002-9458-0282], Dwek, Miriam [0000-0001-7184-2932], Ekici, Arif B [0000-0001-6099-7066], Fasching, Peter A [0000-0003-4885-8471], García-Sáenz, José A [0000-0001-6880-0301], Gayther, Simon A [0000-0001-7937-5443], Giles, Graham G [0000-0003-4946-9099], Greene, Mark H [0000-0003-1852-9239], Guénel, Pascal [0000-0002-8359-518X], Harkness, Elaine F [0000-0001-6625-7739], Heemskerk-Gerritsen, Bernadette AM [0000-0002-9724-6693], Hollestelle, Antoinette [0000-0003-1166-1966], Huebner, Hanna [0000-0001-6889-1493], Hulick, Peter J [0000-0001-8397-4078], Jakimovska, Milena [0000-0002-1506-0669], Jakubowska, Anna [0000-0002-5650-0501], James, Paul [0000-0002-4361-4657], Jones, Michael E [0000-0001-7479-3451], Kapoor, Pooja Middha [0000-0001-5503-8215], Keeman, Renske [0000-0002-5452-9933], Konstantopoulou, Irene [0000-0002-0470-0309], Larsson, Susanna C [0000-0003-0118-0341], Laurent-Puig, Pierre [0000-0001-8475-5459], Leslie, Goska [0000-0001-5756-6222], Lesueur, Fabienne [0000-0001-7404-4549], Lissowska, Jolanta [0000-0003-2695-5799], Matricardi, Laura [0000-0002-0241-1810], McLean, Catriona [0000-0002-0302-5727], Menon, Usha [0000-0003-3708-1732], Miller, Austin [0000-0001-9739-8462], Muranen, Taru A [0000-0002-5895-1808], Nathanson, Katherine L [0000-0002-6740-0901], Nevanlinna, Heli [0000-0002-0916-2976], Newman, William G [0000-0002-6382-4678], Olopade, Olufunmilayo I [0000-0002-9936-1599], Orr, Nick [0000-0003-2866-942X], Parsons, Michael T [0000-0003-3242-8477], Peshkin, Beth [0000-0002-2997-4701], Peterlongo, Paolo [0000-0001-6951-6855], Peto, Julian [0000-0002-1685-8912], Plaseska-Karanfilska, Dijana [0000-0001-8877-2416], Radice, Paolo [0000-0001-6298-4111], Rennert, Gad [0000-0002-8512-068X], Romero, Atocha [0000-0002-1634-7397], Saloustros, Emmanouil [0000-0002-0485-0120], Stone, Jennifer [0000-0001-5077-0124], Teixeira, Manuel R [0000-0002-4896-5982], Toland, Amanda E [0000-0002-0271-1792], Tomlinson, Ian [0000-0003-3037-1470], van Veen, Elke M [0000-0001-8618-2332], vanRensburg, Elizabeth J [0000-0003-2077-230X], Weitzel, Jeffrey N [0000-0001-6714-092X], Winqvist, Robert [0000-0003-0932-9104], Wolk, Alicja [0000-0001-7387-6845], Yannoukakos, Drakoulis [0000-0001-7509-3510], Zheng, Wei [0000-0003-1226-070X], Milne, Roger L [0000-0001-5764-7268], Kraft, Peter [0000-0002-4472-8103], Simard, Jacques [0000-0001-6906-3390], Pharoah, Paul DP [0000-0001-8494-732X], Michailidou, Kyriaki [0000-0001-7065-1237], Schmidt, Marjanka K [0000-0002-2228-429X], Easton, Douglas F [0000-0003-2444-3247], Chatterjee, Nilanjan [0000-0002-9060-008X], García-Closas, Montserrat [0000-0003-1033-2650], and Apollo - University of Cambridge Repository

Subjects
BRCA1 Protein, Case-Control Studies, Mutation, Humans, Breast Neoplasms, Female, Genetic Predisposition to Disease, Triple Negative Breast Neoplasms, Linkage Disequilibrium, Genome-Wide Association Study
Abstract

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype1-3. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P

Published
2020

19. Transcriptome‐wide association study of breast cancer risk by estrogen‐receptor status

Author

Feng, Helian, Gusev, Alexander, Pasaniuc, Bogdan, Wu, Lang, Long, Jirong, Abu-Full, Zomoroda, Aittomäki, Kristiina, Andrulis, Irene L, Anton-Culver, Hoda, Antoniou, Antonis C, Arason, Adalgeir, Arndt, Volker, Aronson, Kristan J, Arun, Banu K, Asseryanis, Ella, Auer, Paul L, Azzollini, Jacopo, Balmaña, Judith, Barkardottir, Rosa B, Barnes, Daniel R, Barrowdale, Daniel, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Białkowska, Katarzyna, Blanco, Ana, Blomqvist, Carl, Boeckx, Bram, Bogdanova, Natalia V, Bojesen, Stig E, Bolla, Manjeet K, Bonanni, Bernardo, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Broeks, Annegien, Brüning, Thomas, Burwinkel, Barbara, Cai, Qiuyin, Caldés, Trinidad, Caligo, Maria A, Campbell, Ian, Canisius, Sander, Campa, Daniele, Carter, Brian D, Carter, Jonathan, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Christiansen, Hans, Chung, Wendy K, Claes, Kathleen BM, Clarke, Christine L, GEMO Study Collaborators, EMBRACE Collaborators, GC-HBOC study Collaborators, Couch, Fergus J, Cox, Angela, Cross, Simon S, Cybulski, Cezary, Czene, Kamila, Daly, Mary B, de la Hoya, Miguel, De Leeneer, Kim, Dennis, Joe, Devilee, Peter, Diez, Orland, Domchek, Susan M, Dörk, Thilo, Dos-Santos-Silva, Isabel, Dunning, Alison M, Dwek, Miriam, Eccles, Diana M, Ejlertsen, Bent, Ellberg, Carolina, Engel, Christoph, Eriksson, Mikael, Fasching, Peter A, Fletcher, Olivia, Flyger, Henrik, Fostira, Florentia, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gabrielson, Marike, Ganz, Patricia A, Gapstur, Susan M, Garber, Judy, García-Closas, Montserrat, García-Sáenz, José A, Gaudet, Mia M, Giles, Graham G, Glendon, Gord, Godwin, Andrew K, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Greene, Mark H, Gronwald, Jacek, Guénel, Pascal, Haiman, Christopher A, Hall, Per, Hamann, Ute, Hake, Christopher, He, Wei, Heyworth, Jane, Hogervorst, Frans BL, Hollestelle, Antoinette, Hooning, Maartje J, Hoover, Robert N, Hopper, John L, Huang, Guanmengqian, Hulick, Peter J, Humphreys, Keith, Imyanitov, Evgeny N, ABCTB Investigators, HEBON Investigators, BCFR Investigators, OCGN Investigators, Isaacs, Claudine, Jakimovska, Milena, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Jankowitz, Rachel C, John, Esther M, Johnson, Nichola, Joseph, Vijai, Jung, Audrey, Karlan, Beth Y, Khusnutdinova, Elza, Kiiski, Johanna I, Konstantopoulou, Irene, Kristensen, Vessela N, Laitman, Yael, Lambrechts, Diether, Lazaro, Conxi, Leroux, Dominique, Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Lindor, Noralane, Lindström, Sara, Lo, Wing-Yee, Loud, Jennifer T, Lubiński, Jan, Makalic, Enes, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martens, John WM, Martinez, Maria E, Matricardi, Laura, Maurer, Tabea, Mavroudis, Dimitrios, McGuffog, Lesley, Meindl, Alfons, Menon, Usha, Michailidou, Kyriaki, Kapoor, Pooja M, Miller, Austin, Montagna, Marco, Moreno, Fernando, Moserle, Lidia, Mulligan, Anna M, Muranen, Taru A, Nathanson, Katherine L, Neuhausen, Susan L, Nevanlinna, Heli, Nevelsteen, Ines, Nielsen, Finn C, Nikitina-Zake, Liene, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I, Olsson, Håkan, Osorio, Ana, Papp, Janos, Park-Simon, Tjoung-Won, Parsons, Michael T, Pedersen, Inge S, Peixoto, Ana, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul DP, Phillips, Kelly-Anne, Plaseska-Karanfilska, Dijana, Poppe, Bruce, Pradhan, Nisha, Prajzendanc, Karolina, Presneau, Nadege, Punie, Kevin, Pylkäs, Katri, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad Usman, Rennert, Gad, Risch, Harvey A, Robson, Mark, Romero, Atocha, Saloustros, Emmanouil, Sandler, Dale P, Santos, Catarina, Sawyer, Elinor J, Schmidt, Marjanka K, Schmidt, Daniel F, Schmutzler, Rita K, Schoemaker, Minouk J, Scott, Rodney J, Sharma, Priyanka, Shu, Xiao-Ou, Simard, Jacques, Singer, Christian F, Skytte, Anne-Bine, Soucy, Penny, Southey, Melissa C, Spinelli, John J, Spurdle, Amanda B, Stone, Jennifer, Swerdlow, Anthony J, Tapper, William J, Taylor, Jack A, Teixeira, Manuel R, Terry, Mary Beth, Teulé, Alex, Thomassen, Mads, Thöne, Kathrin, Thull, Darcy L, Tischkowitz, Marc, Toland, Amanda E, Tollenaar, Rob AEM, Torres, Diana, Truong, Thérèse, Tung, Nadine, Vachon, Celine M, van Asperen, Christi J, van den Ouweland, Ans MW, van Rensburg, Elizabeth J, Vega, Ana, Viel, Alessandra, Vieiro-Balo, Paula, Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R, Weitzel, Jeffrey N, Wendt, Camilla, Winqvist, Robert, Yang, Xiaohong R, Yannoukakos, Drakoulis, Ziogas, Argyrios, Milne, Roger L, Easton, Douglas F, Chenevix-Trench, Georgia, Zheng, Wei, Kraft, Peter, Jiang, Xia, Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Antoniou, Antonis [0000-0001-9223-3116], Barnes, Daniel [0000-0002-3781-7570], Dennis, Joe [0000-0003-4591-1214], Dunning, Alison [0000-0001-6651-7166], Leslie, Goska [0000-0001-5756-6222], Pharoah, Paul [0000-0001-8494-732X], Tischkowitz, Marc [0000-0002-7880-0628], Easton, Douglas [0000-0003-2444-3247], Apollo - University of Cambridge Repository, Medical Oncology, Clinical Genetics, Medicum, Research Programs Unit, Genome-Scale Biology (GSB) Research Program, HUSLAB, Department of Medical and Clinical Genetics, Helsinki University Hospital Area, University of Helsinki, HUS Comprehensive Cancer Center, Department of Oncology, Clinicum, INDIVIDRUG - Individualized Drug Therapy, HUS Gynecology and Obstetrics, Department of Obstetrics and Gynecology, Biosciences, Institut Català de la Salut, [Feng H] Program in Genetic Epidemiology and Statistical Genetics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts. Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts. Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts. [Gusev A] Dana‐Farber Cancer Institute, Boston, Massachusetts. [Pasaniuc B] UCLA Path & Lab Med, Los Angeles, California. [Wu L] Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii. [Long J] Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt‐Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee. [Abu-full Z] Clalit National Cancer Control Center, Carmel Medical Center and Technion Faculty of Medicine, Haifa, Israel. [Balmaña J] High Risk and Cancer Prevention Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Diez O] Hereditary Cancer Genetics Group, Area of Clinical and Molecular Genetics, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Vall d'Hebron Hospital Universitari, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus

Subjects
Oncology, Epidemiology, Neoplasms::Neoplasms by Site::Breast Neoplasms [DISEASES], Genetic Phenomena::Genotype::Genetic Predisposition to Disease [PHENOMENA AND PROCESSES], Vesicular Transport Proteins, Estrogen receptor, Genome-wide association study, VARIANTS, Transcriptome, Breast cancer, Brjóstakrabbamein, Receptors, Medicine and Health Sciences, GWAS, skin and connective tissue diseases, Estrogen Receptor Status, Genetics (clinical), Genetics & Heredity, neoplasias::neoplasias por localización::neoplasias de la mama [ENFERMEDADES], 0303 health sciences, Gen, 030305 genetics & heredity, 1184 Genetics, developmental biology, physiology, Causal gene, Genomics, CARRIERS, STATISTICS, 3. Good health, Receptors, Estrogen, breast cancer subtype, causal gene, TWAS, Breast Neoplasms, Estrogens, Female, Genetic Predisposition to Disease, Humans, Risk Assessment, Genome-Wide Association Study, Medical genetics, Breast Cancer Genetics, Erfðarannsóknir, Life Sciences & Biomedicine, EXPRESSION, medicine.medical_specialty, SUSCEPTIBILITY LOCI, 3122 Cancers, Estrògens, Biology, Article, Càncer de mama, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, Krabbameinsrannsóknir, medicine, fenómenos genéticos::genotipo::predisposición genética a la enfermedad [FENÓMENOS Y PROCESOS], 030304 developmental biology, Genetic association, Science & Technology, IDENTIFICATION, medicine.disease, Estrogen, TISSUE, Breast cancer subtype, Mama - Càncer - Aspectes genètics, Mathematical & Computational Biology
Abstract

Publisher's version (útgefin grein), Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER−). We further compared associations with ER+ and ER− subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER– breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER− breast cancer., The authors thank the Cellex Foundation for providing research facilities and equipment. The breast cancer genome‐wide association (BCAC) is funded by Cancer Research UK (C1287/A16563, C1287/A10118), the European Union's Horizon 2020 Research and Innovation Programme (grant nos. 634935 and 633784 for BRIDGES and B‐CAST, respectively), and by the European Community's Seventh Framework Programme under grant agreement number 223175 (grant no. HEALTH‐F2‐2009‐223175) (COGS). The EU Horizon 2020 Research and Innovation Programme funding source had no role in study design, data collection, data analysis, data interpretation or writing of the report. Genotyping of the OncoArray was funded by the NIH grant U19 CA148065, and Cancer UK grant C1287/A16563 and the PERSPECTIVE project supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (grant GPH‐129344), and the Ministère de l’Économie, Science et Innovation du Québec through Genome Québec and the PSRSIIRI‐701 grant, and the Quebec Breast Cancer Foundation. Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement no. 223175 (HEALTH‐F2‐2009‐223175; COGS), Cancer Research UK (C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, and C8197/A16565), the National Institutes of Health (CA128978) and Post‐Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065, and 1U19 CA148112—the GAME‐ON initiative), the Department of Defence (W81XWH‐10‐1‐0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, and Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The DRIVE Consortium was funded by U19 CA148065. The Australian Breast Cancer Family Study (ABCFS) was supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The ABCFS was also supported by the National Health and Medical Research Council of Australia, the New South Wales Cancer Council, the Victorian Health Promotion Foundation (Australia) and the Victorian Breast Cancer Research Consortium. J. L. H. is a National Health and Medical Research Council (NHMRC) Senior Principal Research Fellow. M. C. S. is an NHMRC Senior Research Fellow. The ABCS study was supported by the Dutch Cancer Society (grants NKI 2007‐3839; 2009 4363). The Australian Breast Cancer Tissue Bank (ABCTB) is generously supported by the National Health and Medical Research Council of Australia, The Cancer Institute NSW and the National Breast Cancer Foundation. The ACP study is funded by the Breast Cancer Research Trust, UK. The AHS study is supported by the intramural research program of the National Institutes of Health, the National Cancer Institute (grant no. Z01‐CP010119), and the National Institute of Environmental Health Sciences (grant no. Z01‐ES049030). The work of the BBCC was partly funded by ELAN‐Fond of the University Hospital of Erlangen. The BBCS is funded by Cancer Research UK and Breast Cancer Now and acknowledges NHS funding to the NIHR Biomedical Research Centre, and the National Cancer Research Network (NCRN). The BCEES was funded by the National Health and Medical Research Council, Australia and the Cancer Council Western Australia and acknowledges funding from the National Breast Cancer Foundation (JS). For the BCFR‐NY, BCFR‐PA, BCFR‐UT this work was supported by grant UM1 CA164920 from the National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government or the BCFR. For BIGGS, E. S. is supported by NIHR Comprehensive Biomedical Research Centre, Guy's and St. Thomas' NHS Foundation Trust in partnership with King's College London, United Kingdom. I. T. is supported by the Oxford Biomedical Research Centre. B. O. C. S. is supported by funds from Cancer Research UK (C8620/A8372/A15106) and the Institute of Cancer Research (UK). B. O. C. S. acknowledges NHS funding to the Royal Marsden/Institute of Cancer Research NIHR Specialist Cancer Biomedical Research Centre. The BREast Oncology GAlician Network (BREOGAN) is funded by Acción Estratégica de Salud del Instituto de Salud Carlos III FIS PI12/02125/Cofinanciado FEDER; Acción Estratégica de Salud del Instituto de Salud Carlos III FIS Intrasalud (PI13/01136); Programa Grupos Emergentes, Cancer Genetics Unit, Instituto de Investigacion Biomedica Galicia Sur. Xerencia de Xestion Integrada de Vigo‐SERGAS, Instituto de Salud Carlos III, Spain; Grant 10CSA012E, Consellería de Industria Programa Sectorial de Investigación Aplicada, PEME I + D e I + D Suma del Plan Gallego de Investigación, Desarrollo e Innovación Tecnológica de la Consellería de Industria de la Xunta de Galicia, Spain (grant EC11‐192). Fomento de la Investigación Clínica Independiente, Ministerio de Sanidad, Servicios Sociales e Igualdad, Spain; and Grant FEDER‐Innterconecta. Ministerio de Economia y Competitividad, Xunta de Galicia, Spain. The BSUCH study was supported by the Dietmar‐Hopp Foundation, the Helmholtz Society and the German Cancer Research Center (DKFZ). The CAMA study was funded by Consejo Nacional de Ciencia y Tecnología (CONACyT; SALUD‐2002‐C01‐7462). Sample collection and processing were funded in part by grants from the National Cancer Institute (NCI R01CA120120 and K24CA169004). C. B. C. S. is funded by the Canadian Cancer Society (grant no. 313404) and the Canadian Institutes of Health Research. C. C. G. P. is supported by funding from the University of Crete. The CECILE study was supported by Fondation de France, Institut National du Cancer (INCa), Ligue Nationale Contre le Cancer, Agence Nationale de Sécurité Sanitaire, de l'Alimentation, de l'Environnement et du Travail (ANSES), Agence Nationale de la Recherche (ANR). The CGPS was supported by the Chief Physician Johan Boserup and Lise Boserup Fund, the Danish Medical Research Council, and Herlev and Gentofte Hospital. The CNIO‐BCS was supported by the Instituto de Salud Carlos III, the Red Temática de Investigación Cooperativa en Cáncer and grants from the Asociación Española Contra el Cáncer and the Fondo de Investigación Sanitario (PI11/00923 and PI12/00070). COLBCCC is supported by the German Cancer Research Center (DKFZ), Heidelberg, Germany. Diana Torres was in part supported by a postdoctoral fellowship from the Alexander von Humboldt Foundation. The American Cancer Society funds the creation, maintenance, and updating of the CPS‐II cohort. The CTS was initially supported by the California Breast Cancer Act of 1993 and the California Breast Cancer Research Fund (contract 97‐10500) and is currently funded through the National Institutes of Health (R01 CA77398, UM1 CA164917, and U01 CA199277). The collection of cancer incidence data was supported by the California Department of Public Health as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. HAC receives support from the Lon V Smith Foundation (LVS39420). The University of Westminster curates the DietCompLyf database funded by Against Breast Cancer Registered Charity No. 1121258 and the NCRN. The coordination of EPIC is financially supported by the European Commission (DG‐SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF) (Germany); the Hellenic Health Foundation, the Stavros Niarchos Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro‐AIRC‐Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), PI13/00061 to Granada, PI13/01162 to EPIC‐Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Cancer Research UK (14136 to EPIC‐Norfolk; C570/A16491 and C8221/A19170 to EPIC‐Oxford), Medical Research Council (1000143 to EPIC‐Norfolk, MR/M012190/1 to EPIC‐Oxford) (United Kingdom). The ESTHER study was supported by a grant from the Baden Württemberg Ministry of Science, Research and Arts. Additional cases were recruited in the context of the VERDI study, which was supported by a grant from the German Cancer Aid (Deutsche Krebshilfe). FHRISK is funded from NIHR grant PGfAR 0707‐10031. The GC‐HBOC (German Consortium of Hereditary Breast and Ovarian Cancer) is supported by the German Cancer Aid (grant no 110837, coordinator: Rita K. Schmutzler, Cologne). This work was also funded by the European Regional Development Fund and Free State of Saxony, Germany (LIFE—Leipzig Research Centre for Civilization Diseases, project numbers 713‐241202, 713‐241202, 14505/2470, 14575/2470). The GENICA was funded by the Federal Ministry of Education and Research (BMBF) Germany grants 01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, the Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bochum, as well as the Department of Internal Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany. The GEPARSIXTO study was conducted by the German Breast Group GmbH. The GESBC was supported by the Deutsche Krebshilfe e. V. (70492) and the German Cancer Research Center (DKFZ). GLACIER was supported by Breast Cancer Now, CRUK and Biomedical Research Centre at Guy's and St Thomas’ NHS Foundation Trust and King's College London. The HABCS study was supported by the Claudia von Schilling Foundation for Breast Cancer Research, by the Lower Saxonian Cancer Society, and by the Rudolf Bartling Foundation. The HEBCS was financially supported by the Helsinki University Hospital Research Fund, the Finnish Cancer Society, and the Sigrid Juselius Foundation. The HERPACC was supported by MEXT Kakenhi (No. 170150181 and 26253041) from the Ministry of Education, Science, Sports, Culture and Technology of Japan, by a Grant‐in‐Aid for the Third Term Comprehensive 10‐Year Strategy for Cancer Control from Ministry Health, Labour and Welfare of Japan, by Health and Labour Sciences Research Grants for Research on Applying Health Technology from Ministry Health, Labour and Welfare of Japan, by National Cancer Center Research and Development Fund, and “Practical Research for Innovative Cancer Control (15ck0106177h0001)” from Japan Agency for Medical Research and development, AMED, and Cancer Bio Bank Aichi. The HMBCS was supported by a grant from the Friends of Hannover Medical School and by the Rudolf Bartling Foundation. The HUBCS was supported by a grant from the German Federal Ministry of Research and Education (RUS08/017) and by the Russian Foundation for Basic Research and the Federal Agency for Scientific Organizations for supporting the Bioresource collections and RFBR grants 14‐04‐97088, 17‐29‐06014, and 17‐44‐020498. ICICLE was supported by Breast Cancer Now, CRUK and Biomedical Research Centre at Guy's and St Thomas’ NHS Foundation Trust and King's College London. Financial support for KARBAC was provided through the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Swedish Cancer Society, The Gustav V Jubilee foundation and Bert von Kantzows foundation. The KARMA study was supported by Märit and Hans Rausings Initiative Against Breast Cancer. The KBCP was financially supported by the special Government Funding (EVO) of Kuopio University Hospital grants, Cancer Fund of North Savo, the Finnish Cancer Organizations, and the strategic funding of the University of Eastern Finland. The kConFab Follow‐Up Study is supported by grants from Cancer Australia, the Australian National Breast Cancer Foundation, the National Health and Medical Research Council, the National Institute of Health USA, the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. KAP is an Australian National Breast Cancer Foundation Practitioner Fellow. Financial support for the AOCS was provided by the United States Army Medical Research and Materiel Command (DAMD17‐01‐1‐0729), Cancer Council Victoria, Queensland Cancer Fund, Cancer Council New South Wales, Cancer Council South Australia, The Cancer Foundation of Western Australia, Cancer Council Tasmania and the National Health and Medical Research Council of Australia (NHMRC; 400413, 400281, and 199600). G. C. T. and P. W. are supported by the NHMRC. R. B. was a Cancer Institute NSW Clinical Research Fellow. The KOHBRA study was partially supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), and the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (HI16C1127; 1020350; 1420190). L. A. A. B. C. is supported by grants (1RB‐0287, 3PB‐0102, 5PB‐0018, and 10PB‐0098) from the California Breast Cancer Research Program. Incident breast cancer cases were collected by the USC Cancer Surveillance Program (CSP) which is supported under subcontract by the California Department of Health. The CSP is also part of the National Cancer Institute's Division of Cancer Prevention and Control Surveillance, Epidemiology, and End Results Program, under contract number N01CN25403. L. M. B. C. is supported by the “Stichting tegen Kanker.” D. L. is supported by the FWO. The MABCS study is funded by the Research Centre for Genetic Engineering and Biotechnology “Georgi D. Efremov” and supported by the German Academic Exchange Program, DAAD. The MARIE study was supported by the Deutsche Krebshilfe e.V. (70‐2892‐BR I, 106332, 108253, 108419, 110826, 110828), the Hamburg Cancer Society, the German Cancer Research Center (DKFZ) and the Federal Ministry of Education and Research (BMBF) Germany (01KH0402). MBCSG is supported by grants from the Italian Association for Cancer Research (AIRC) and by funds from the Italian citizens who allocated the 5/1,000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT‐Institutional strategic projects “5 × 1,000”). The MCBCS was supported by the NIH grants CA192393, CA116167, CA176785, and NIH Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), and the Breast Cancer Research Foundation and a generous gift from the David F. and Margaret T. Grohne Family Foundation. The Melbourne Collaborative Cohort Study (MCCS) cohort recruitment was funded by VicHealth and Cancer Council Victoria. The MCCS was further augmented by Australian National Health and Medical Research Council grants 209057, 396414, and 1074383 and by infrastructure provided by Cancer Council Victoria. Cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the National Death Index and the Australian Cancer Database.” The MEC was supported by NIH grants CA63464, CA54281, CA098758, CA132839, and CA164973. The MISS study is supported by funding from ERC‐2011‐294576 Advanced grant, Swedish Cancer Society, Swedish Research Council, Local hospital funds, Berta Kamprad Foundation, Gunnar Nilsson. The MMHS study was supported by NIH grants CA97396, CA128931, CA116201, CA140286, and CA177150. M. S. K. C. C. is supported by grants from the Breast Cancer Research Foundation and Robert and Kate Niehaus Clinical Cancer Genetics Initiative. The work of MTLGEBCS was supported by the Quebec Breast Cancer Foundation, the Canadian Institutes of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program—grant no. CRN‐87521 and the Ministry of Economic Development, Innovation and Export Trade—grant no. PSR‐SIIRI‐701. MYBRCA is funded by research grants from the Malaysian Ministry of Higher Education (UM.C/HlR/MOHE/06) and Cancer Research Malaysia. MYMAMMO is supported by research grants from Yayasan Sime Darby LPGA Tournament and Malaysian Ministry of Higher Education (RP046B‐15HTM). The NBCS has been supported by the Research Council of Norway grant 193387/V50 (to A.‐L. B.‐D. and V. N. K.) and grant 193387/H10 (to A.‐L. B.‐D. and V. N. K.), South‐Eastern Norway Health Authority (grant 39346 to A.‐L.B‐D. and 27208 to V. N. K.) and the Norwegian Cancer Society (to A.‐L. B.‐D. and 419616‐71248‐PR‐2006‐0282 to V. N. K.). It has received funding from the K.G. Jebsen Centre for Breast Cancer Research (2012‐2015). The NBHS was supported by NIH grant R01CA100374. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The Northern California Breast Cancer Family Registry (NC‐BCFR) and Ontario Familial Breast Cancer Registry (OFBCR) were supported by grant UM1 CA164920 from the National Cancer Institute (USA). The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the Breast Cancer Family Registry (BCFR), nor does mention of trade names, commercial products, or organizations imply endorsement by the USA Government or the BCFR. The Carolina Breast Cancer Study was funded by Komen Foundation, the National Cancer Institute (P50 CA058223, U54 CA156733, and U01 CA179715), and the North Carolina University Cancer Research Fund. The NGOBCS was supported by Grants‐in‐Aid for the Third Term Comprehensive Ten‐Year Strategy for Cancer Control from the Ministry of Health, Labor and Welfare of Japan, and for Scientific Research on Priority Areas, 17015049 and for Scientific Research on Innovative Areas, 221S0001, from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. The NHS was supported by NIH grants P01 CA87969, UM1 CA186107, and U19 CA148065. The NHS2 was supported by NIH grants UM1 CA176726 and U19 CA148065. The OBCS was supported by research grants from the Finnish Cancer Foundation, the Academy of Finland (grant no. 250083, 122715 and Center of Excellence grant no. 251314), the Finnish Cancer Foundation, the Sigrid Juselius Foundation, the University of Oulu, the University of Oulu Support Foundation and the special Governmental EVO funds for Oulu University Hospital‐based research activities. The ORIGO study was supported by the Dutch Cancer Society (RUL 1997‐1505) and the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI‐NL CP16). The PBCS was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. Genotyping for PLCO was supported by the Intramural Research Program of the National Institutes of Health, NCI, Division of Cancer Epidemiology and Genetics. The PLCO is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and supported by contracts from the Division of Cancer Prevention, National Cancer Institute, National Institutes of Health. The POSH study is funded by Cancer Research UK (grants C1275/A11699, C1275/C22524, C1275/A19187, C1275/A15956, and Breast Cancer Campaign 2010PR62, 2013PR044. PROCAS is funded from NIHR grant PGfAR 0707‐10031. The RBCS was funded by the Dutch Cancer Society (DDHK 2004‐3124, DDHK 2009‐4318). The SASBAC study was supported by funding from the Agency for Science, Technology, and Research of Singapore (A*STAR), the US National Institute of Health (NIH) and the Susan G. Komen Breast Cancer Foundation. The SBCGS was supported primarily by NIH grants R01CA64277, R01CA148667, UMCA182910, and R37CA70867. Biological sample preparation was conducted the Survey and Biospecimen Shared Resource, which is supported by P30 CA68485. The scientific development and funding of this project were, in part, supported by the Genetic Associations and Mechanisms in Oncology (GAME‐ON) Network U19 CA148065. The SBCS was supported by Sheffield Experimental Cancer Medicine Centre and Breast Cancer Now Tissue Bank. The SCCS is supported by a grant from the National Institutes of Health (R01 CA092447). Data on SCCS cancer cases used in this publication were provided by the Alabama Statewide Cancer Registry; Kentucky Cancer Registry, Lexington, KY; Tennessee Department of Health, Office of Cancer Surveillance; Florida Cancer Data System; North Carolina Central Cancer Registry, North Carolina Division of Public Health; Georgia Comprehensive Cancer Registry; Louisiana Tumor Registry; Mississippi Cancer Registry; South Carolina Central Cancer Registry; Virginia Department of Health, Virginia Cancer Registry; Arkansas Department of Health, Cancer Registry, 4815 W. Markham, Little Rock, AR 72205. The Arkansas Central Cancer Registry is fully funded by a grant from the National Program of Cancer Registries, Centers for Disease Control and Prevention (CDC). Data on SCCS cancer cases from Mississippi were collected by the Mississippi Cancer Registry which participates in the National Program of Cancer Registries (NPCR) of the Centers for Disease Control and Prevention (CDC). The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the CDC or the Mississippi Cancer Registry. SEARCH is funded by Cancer Research UK (C490/A10124 and C490/A16561) and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge. The University of Cambridge has received salary support for PDPP from the NHS in the East of England through the Clinical Academic Reserve. SEBCS was supported by the BRL (Basic Research Laboratory) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2012‐0000347). SGBCC is funded by the NUS start‐up Grant, National University Cancer Institute Singapore (NCIS) Centre Grant and the NMRC Clinician Scientist Award. Additional controls were recruited by the Singapore Consortium of Cohort Studies‐Multi‐ethnic cohort (SCCS‐MEC), which was funded by the Biomedical Research Council, grant no. 05/1/21/19/425. The Sister Study (SISTER) is supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01‐ES044005 and Z01‐ES049033). The Two Sister Study (2SISTER) was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01‐ES044005 and Z01‐ES102245), and, also by a grant from Susan G. Komen for the Cure, grant FAS0703856. SKKDKFZS is supported by the DKFZ. The SMC is funded by the Swedish Cancer Foundation. The SZBCS and IHCC were supported by Grant PBZ_KBN_122/P05/2004 and the program of the Minister of Science and Higher Education under the name “Regional Initiative of Excellence” in 2019–2022 project number 002/RID/2018/19 amount of financing 12,000,000 PLN. The TBCS was funded by The National Cancer Institute of Thailand. The TNBCC was supported by a Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), a grant from the Breast Cancer Research Foundation, a generous gift from the David F. and Margaret T. Grohne Family Foundation. The TWBCS is supported by the Taiwan Biobank project of the Institute of Biomedical Sciences, Academia Sinica, Taiwan. The UCIBCS component of this research was supported by the NIH (CA58860 and CA92044) and the Lon V Smith Foundation (LVS39420). The UKBGS is funded by Breast Cancer Now and the Institute of Cancer Research (ICR), London and also thank the study participants, study staff, and the doctors, nurses and other health care providers and health information sources who have contributed to the study. ICR acknowledges NHS funding to the NIHR Biomedical Research Centre. The UKOPS study was funded by The Eve Appeal (The Oak Foundation) and supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The US3SS study was supported by Massachusetts (K. M. E., R01CA47305), Wisconsin (P. A. N., R01 CA47147), and New Hampshire (L. T.‐E., R01CA69664) centers, and Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The USRT Study was funded by Intramural Research Funds of the National Cancer Institute, Department of Health and Human Services, USA. The WAABCS study was supported by grants from the National Cancer Institute of the National Institutes of Health (R01 CA89085 and P50 CA125183 and the D43 TW009112 grant), Susan G. Komen (SAC110026), Dr. Ralph and Marian Falk Medical Research Trust, and the Avon Foundation for Women. The WHI program is funded by the National Heart, Lung, and Blood Institute, the US National Institutes of Health and the US Department of Health and Human Services (HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C). This work was also funded by NCI U19 CA148065‐01. D. G. E. is supported by the all Manchester NIHR Biomedical research center Manchester (IS‐BRC‐1215‐20007). HUNBOCS, Hungarian Breast, and Ovarian Cancer Study were supported by Hungarian Research Grant KTIA‐OTKA CK‐80745, NKFI_OTKA K‐112228. C. I. received support from the Survey, Recruitment, and Biospecimen Shared Resource at Georgetown University (NIH/NCI P30‐CA‐51008) and the Jess and Mildred Fisher Center for Hereditary Cancer and Clinical Genomics Research. K. M. is supported by CRUK C18281/A19169. City of Hope Clinical Cancer Community Research Network and the Hereditary Cancer Research Registry, supported in part by Award Number RC4CA153828 (PI: J Weitzel) from the National Cancer Institute and the office of the Director, National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The ICO study is supported by the Asociación Española Contra el Cáncer (AECC), The Instituto de Salud Carlos III (organismo adscrito al Ministerio de Economía y Competitividad) and “Fondo Europeo de Desarrollo Regional (FEDER), una manera de hacer Europa” (PI10/01422, PI13/00285, PIE13/00022, PI15/00854, PI16/00563, and CIBERONC) and The Institut Català de la Salut and Autonomous Government of Catalonia (2009SGR290, 2014SGR338 and PERIS Project MedPerCan). Dr. Beth Karlan is funded by the American Cancer Society Early Detection Professorship (SIOP‐06‐258‐01‐COUN) and the National Center for Advancing Translational Sciences (NCATS), grant UL1TR000124. A.V. is supported by the Spanish Health Research Foundation, Instituto de Salud Carlos III (ISCIII), partially supported by FEDER funds through Research Activity Intensification Program (contract grant nos. INT15/00070, INT16/00154, INT17/00133), and through Centro de Investigación Biomédica en Red de Enferemdades Raras CIBERER (ACCI 2016: ER17P1AC7112/2018); Autonomous Government of Galicia (Consolidation and structuring program: IN607B), and by the Fundación Mutua Madrileña (call 2018). The GEMO resource was initially funded by the French National Institute of Cancer (INCa, PHRC Ile de France, grant AOR 01 082, 2001–2003, grant 2013‐1‐BCB‐01‐ICH‐1), the Association “Le cancer du sein, parlons‐en!” Award (2004) the Association for International Cancer Research (2008–2010), and the Fondation ARC pour la recherche sur le cancer (grant PJA 20151203365). It also received support from the Canadian Institute of Health Research for the “CIHR Team in Familial Risks of Breast Cancer” program (2008–2013), and the European commission FP7, Project «Collaborative Ovarian, breast and prostate Gene‐environment Study (COGS), Large‐scale integrating project» (2009–2013). G. E. M. O. is currently supported by the INCa grant SHS‐E‐SP 18‐015. OSUCCC was funded by the Ohio State University Comprehensive Cancer Center. Leigha Senter, Kevin Sweet, Caroline Craven, Julia Cooper, Amber Aielts, and Michelle O'Conor aided in the recruitment of BRCA1/2 study participants and data collection. Robert Pilarski aided in recruitment and data collection of TNBC cases from the Stefanie Spielman Breast Bank. Clinical Genetics Branch, NCI: the Intramural Research Program of the US National Cancer Institute, NIH, Division of Cancer Epidemiology and Genetics, and by support services contracts NO2‐CP‐11019‐50, N02‐CP‐21013‐63 and N02‐CP‐65504 with Westat, Inc, Rockville, MD. ILUH was funded by the Icelandic Association “Walking for Breast Cancer Research” and by the Landspitali University Hospital Research Fund. The Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON) consists of the following Collaborating Centers: Netherlands Cancer Institute (coordinating center), Amsterdam, NL: M.A. Rookus, F.B.L. Hogervorst, F.E. van Leeuwen, M.A. Adank, M.K. Schmidt, D.J. Jenner; Erasmus Medical Center, Rotterdam, NL: J.M. Collée, A.M.W. van den Ouweland, M.J. Hooning, I.A. Boere; Leiden University Medical Center, NL: C.J. van Asperen, P. Devilee, R.B. van der Luijt, T.C.T.E.F. van Cronenburg; Radboud University Nijmegen Medical Center, NL: M.R. Wevers, A.R. Mensenkamp; University Medical Center Utrecht, NL: M.G.E.M. Ausems, M.J. Koudijs; Amsterdam Medical Center, NL: E.J. Meijers‐Heijboer, T.A.M. van Os; VU University Medical Center, Amsterdam, NL: K. van Engelen, J.J.P. Gille; Maastricht University Medical Center, NL: E.B. Gómez‐Garcia, M.J. Blok, M. de Boer; University of Groningen, NL: J.C. Oosterwijk, A.H. van der Hout, M.J.E. Mourits, G.H. de Bock; The Netherlands Comprehensive Cancer Organisation (IKNL): S. Siesling, J. Verloop; The nationwide network and registry of histo‐ and cyto‐pathology in the Netherlands (PALGA): E.C. van den Broek. HEBON thanks the study participants and the registration teams of IKNL and PALGA for part of the data collection. The HEBON study is supported by the Dutch Cancer Society grants NKI1998‐1854, NKI2004‐3088, NKI2007‐3756, the Netherlands Organisation of Scientific Research grant NWO 91109024, the Pink Ribbon grants 110005 and 2014‐187.WO76, the BBMRI grant NWO 184.021.007/CP46, and the Transcan grant JTC 2012 Cancer 12‐054. N.N. Petrov Institute of Oncology is supported by the Russian Foundation for Basic Research (grants 17‐00‐00171, 18‐515‐45012 and 19‐515‐25001).

Published
2020

20. Genome-wide association study of germline variants and breast cancer-specific mortality

Author

Escala-Garcia, Maria, Guo, Qi, Dörk, Thilo, Canisius, Sander, Keeman, Renske, Dennis, Joe, Beesley, Jonathan, Lecarpentier, Julie, Bolla, Manjeet K, Wang, Qin, Abraham, Jean, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Auer, Paul L, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Bernstein, Leslie, Blomqvist, Carl, Boeckx, Bram, Bojesen, Stig E, Bonanni, Bernardo, Børresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brentnall, Adam, Brinton, Louise, Broberg, Per, Brock, Ian W, Brucker, Sara Y, Burwinkel, Barbara, Caldas, Carlos, Caldés, Trinidad, Campa, Daniele, Canzian, Federico, Carracedo, Angel, Carter, Brian D, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Chenevix-Trench, Georgia, Cheng, Ting-Yuan David, Chin, Suet-Feung, Clarke, Christine L, NBCS Collaborators, Cordina-Duverger, Emilie, Couch, Fergus J, Cox, David G, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Devilee, Peter, Dunn, Janet A, Dunning, Alison M, Durcan, Lorraine, Dwek, Miriam, Earl, Helena M, Ekici, Arif B, Eliassen, A Heather, Ellberg, Carolina, Engel, Christoph, Eriksson, Mikael, Evans, D Gareth, Figueroa, Jonine, Flesch-Janys, Dieter, Flyger, Henrik, Gabrielson, Marike, Gago-Dominguez, Manuela, Galle, Eva, Gapstur, Susan M, García-Closas, Montserrat, García-Sáenz, José A, Gaudet, Mia M, George, Angela, Georgoulias, Vassilios, Giles, Graham G, Glendon, Gord, Goldgar, David E, González-Neira, Anna, Alnæs, Grethe I Grenaker, Grip, Mervi, Guénel, Pascal, Haeberle, Lothar, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hamann, Ute, Hankinson, Susan, Harkness, Elaine F, Harrington, Patricia A, Hart, Steven N, Hartikainen, Jaana M, Hein, Alexander, Hillemanns, Peter, Hiller, Louise, Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J, Hoover, Robert N, Hopper, John L, Howell, Anthony, Huang, Guanmengqian, Humphreys, Keith, Hunter, David J, Janni, Wolfgang, John, Esther M, Jones, Michael E, Jukkola-Vuorinen, Arja, Jung, Audrey, Kaaks, Rudolf, Kabisch, Maria, Kaczmarek, Katarzyna, Kerin, Michael J, Khan, Sofia, Khusnutdinova, Elza, Kiiski, Johanna I, Kitahara, Cari M, Knight, Julia A, Ko, Yon-Dschun, Koppert, Linetta B, Kosma, Veli-Matti, Kraft, Peter, Kristensen, Vessela N, Krüger, Ute, Kühl, Tabea, Lambrechts, Diether, Le Marchand, Loic, Lee, Eunjung, Lejbkowicz, Flavio, Li, Lian, Lindblom, Annika, Lindström, Sara, Linet, Martha, Lissowska, Jolanta, Lo, Wing-Yee, Loibl, Sibylle, Lubiński, Jan, Lux, Michael P, MacInnis, Robert J, Maierthaler, Melanie, Maishman, Tom, Makalic, Enes, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martinez, Maria Elena, Mavroudis, Dimitrios, McLean, Catriona, Meindl, Alfons, Middha, Pooja, Miller, Nicola, Milne, Roger L, Moreno, Fernando, Mulligan, Anna Marie, Mulot, Claire, Nassir, Rami, Neuhausen, Susan L, Newman, William T, Nielsen, Sune F, Nordestgaard, Børge G, Norman, Aaron, Olsson, Håkan, Orr, Nick, Pankratz, V Shane, Park-Simon, Tjoung-Won, Perez, Jose IA, Pérez-Barrios, Clara, Peterlongo, Paolo, Petridis, Christos, Pinchev, Mila, Prajzendanc, Karoliona, Prentice, Ross, Presneau, Nadege, Prokofieva, Darya, Pylkäs, Katri, Rack, Brigitte, Radice, Paolo, Ramachandran, Dhanya, Rennert, Gadi, Rennert, Hedy S, Rhenius, Valerie, Romero, Atocha, Roylance, Rebecca, Saloustros, Emmanouil, Sawyer, Elinor J, Schmidt, Daniel F, Schmutzler, Rita K, Schneeweiss, Andreas, Schoemaker, Minouk J, Schumacher, Fredrick, Schwentner, Lukas, Scott, Rodney J, Scott, Christopher, Seynaeve, Caroline, Shah, Mitul, Simard, Jacques, Smeets, Ann, Sohn, Christof, Southey, Melissa C, Swerdlow, Anthony J, Talhouk, Aline, Tamimi, Rulla M, Tapper, William J, Teixeira, Manuel R, Tengström, Maria, Terry, Mary Beth, Thöne, Kathrin, Tollenaar, Rob AEM, Tomlinson, Ian, Torres, Diana, Truong, Thérèse, Turman, Constance, Turnbull, Clare, Ulmer, Hans-Ulrich, Untch, Michael, Vachon, Celine, van Asperen, Christi J, van den Ouweland, Ans MW, van Veen, Elke M, Wendt, Camilla, Whittemore, Alice S, Willett, Walter, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R, Zhang, Yan, Easton, Douglas F, Fasching, Peter A, Nevanlinna, Heli, Eccles, Diana M, Pharoah, Paul DP, Schmidt, Marjanka K, Dennis, Joe [0000-0003-4591-1214], Wang, Jean [0000-0002-9139-0627], Abraham, Jean [0000-0003-0688-4807], Caldas, Carlos [0000-0003-3547-1489], Chin, Suet-Feung [0000-0001-5697-1082], Dunning, Alison [0000-0001-6651-7166], Earl, Helena [0000-0003-1549-8094], Rhenius, Valerie [0000-0003-4215-3235], Easton, Douglas [0000-0003-2444-3247], Pharoah, Paul [0000-0001-8494-732X], and Apollo - University of Cambridge Repository

Subjects
Receptors, Estrogen, Genetic Variation, Humans, Bayes Theorem, Breast Neoplasms, Female, Prognosis, Chromosomes, Human, Pair 7, White People, Genome-Wide Association Study, Proportional Hazards Models
Abstract

BACKGROUND: We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry. METHODS: Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP). RESULTS: We did not find any variant associated with breast cancer-specific mortality at P

Published
2019

21. Association of breast cancer risk loci with breast cancer survival

Author

Barrdahl, Myrto, Canzian, Federico, Lindström, Sara, Shui, Irene, Black, Amanda, Hoover, Robert N., Ziegler, Regina G., Buring, Julie E., Chanock, Stephen J., Diver, W. Ryan, Gapstur, Susan M., Gaudet, Mia M., Giles, Graham G., Haiman, Christopher, Henderson, Brian E., Hankinson, Susan, Hunter, David J., Joshi, Amit D., Kraft, Peter, Lee, I. Min, Le Marchand, Loic, Milne, Roger L., Southey, Melissa C., Willett, Walter, Gunter, Marc, Panico, Salvatore, Sund, Malin, Weiderpass, Elisabete, Sánchez, María José, Overvad, Kim, Dossus, Laure, Peeters, Petra H., Khaw, Kay Tee, Trichopoulos, Dimitrios, Kaaks, Rudolf, Campa, Daniele, Barrdahl, Myrto, Canzian, Federico, Lindström, Sara, Shui, Irene, Black, Amanda, Hoover, Robert N, Ziegler, Regina G, Buring, Julie E, Chanock, Stephen J, Diver, W. Ryan, Gapstur, Susan M, Gaudet, Mia M, Giles, Graham G, Haiman, Christopher, Henderson, Brian E, Hankinson, Susan, Hunter, David J, Joshi, Amit D, Kraft, Peter, Lee, I. Min, Le Marchand, Loic, Milne, Roger L, Southey, Melissa C, Willett, Walter, Gunter, Marc, Panico, Salvatore, Sund, Malin, Weiderpass, Elisabete, Sánchez, María José, Overvad, Kim, Dossus, Laure, Peeters, Petra H, Khaw, Kay Tee, Trichopoulos, Dimitrio, Kaaks, Rudolf, and Campa, Daniele

Subjects
Cancer Research, SNP, Breast Neoplasms, Genetic Association Studie, Polymorphism, Single Nucleotide, survival, meta-analysi, Article, breast cancer, BPC3, meta-analysis, Research Support, N.I.H., Extramural, Risk Factors, Journal Article, Humans, Genetic Predisposition to Disease, Genetic Association Studies, Proportional Hazards Models, Research Support, N.I.H., Intramural, Oncology, Genetic Loci, Proportional Hazards Model, Female, Research Support, U.S. Gov't, Non-P.H.S, Breast Neoplasm, Human
Abstract

The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival. We examined the associations between 35 breast cancer susceptibility loci and the disease over-all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We also conducted a meta-analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed in silico analyses of SNPs with significant associations. In BPC3, the C allele of LSP1-rs3817198 was significantly associated with improved OS (HRper-allele =0.70; 95% CI: 0.58-0.85; ptrend = 2.84 × 10(-4) ; HRheterozygotes = 0.71; 95% CI: 0.55-0.92; HRhomozygotes = 0.48; 95% CI: 0.31-0.76; p2DF = 1.45 × 10(-3) ). In silico, the C allele of LSP1-rs3817198 was predicted to increase expression of the tumor suppressor cyclin-dependent kinase inhibitor 1C (CDKN1C). In the meta-analysis, TNRC9-rs3803662 was significantly associated with increased death hazard (HRMETA =1.09; 95% CI: 1.04-1.15; ptrend = 6.6 × 10(-4) ; HRheterozygotes = 0.96 95% CI: 0.90-1.03; HRhomozygotes = 1.21; 95% CI: 1.09-1.35; p2DF =1.25 × 10(-4) ). In conclusion, we show that there is little overlap between the breast cancer risk single nucleotide polymorphisms (SNPs) identified so far and the SNPs associated with breast cancer prognosis, with the possible exceptions of LSP1-rs3817198 and TNRC9-rs3803662.

Published
2015

22. Body mass index and breast cancer survival: a Mendelian randomization analysis

Author

Guo, Qi, Burgess, Stephen, Turman, Constance, Bolla, Manjeet K, Wang, Qin, Lush, Michael, Abraham, Jean, Aittomäki, Kristiina, Andrulis, Irene L, Apicella, Carmel, Arndt, Volker, Barrdahl, Myrto, Benitez, Javier, Berg, Christine D, Blomqvist, Carl, Bojesen, Stig E, Bonanni, Bernardo, Brand, Judith S, Brenner, Hermann, Broeks, Annegien, Burwinkel, Barbara, Caldas, Carlos, Campa, Daniele, Canzian, Federico, Chang-Claude, Jenny, Chanock, Stephen J, Chin, Suet-Feung, Couch, Fergus J, Cox, Angela, Cross, Simon S, Cybulski, Cezary, Czene, Kamila, Darabi, Hatef, Devilee, Peter, Diver, W Ryan, Dunning, Alison M, Earl, Helena M, Eccles, Diana M, Ekici, Arif B, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine, Flesch-Janys, Dieter, Flyger, Henrik, Gapstur, Susan M, Gaudet, Mia M, Giles, Graham G, Glendon, Gord, Grip, Mervi, Gronwald, Jacek, Haeberle, Lothar, Haiman, Christopher A, Hall, Per, Hamann, Ute, Hankinson, Susan, Hartikainen, Jaana M, Hein, Alexander, Hiller, Louise, Hogervorst, Frans B, Holleczek, Bernd, Hooning, Maartje J, Hoover, Robert N, Humphreys, Keith, Hunter, David J, Hüsing, Anika, Jakubowska, Anna, Jukkola-Vuorinen, Arja, Kaaks, Rudolf, Kabisch, Maria, Kataja, Vesa, Knight, Julia A, Koppert, Linetta B, Kosma, Veli-Matti, Kristensen, Vessela N, Lambrechts, Diether, Le Marchand, Loic, Li, Jingmei, Lindblom, Annika, Lindström, Sara, Lissowska, Jolanta, Lubinski, Jan, Machiela, Mitchell J, Mannermaa, Arto, Manoukian, Siranoush, Margolin, Sara, Marme, Federik, Martens, John W M, McLean, Catriona, Menéndez, Primitiva, Milne, Roger L, Marie Mulligan, Anna, Muranen, Taru A, Nevanlinna, Heli, Neven, Patrick, Nielsen, Sune F, Nordestgaard, Børge G, Olson, Janet E, Perez, Jose I A, Peterlongo, Paolo, Phillips, Kelly-Anne, Poole, Christopher J, Pylkäs, Katri, Radice, Paolo, Rahman, Nazneen, Rüdiger, Thomas, Rudolph, Anja, Sawyer, Elinor J, Schumacher, Fredrick, Seibold, Petra, Seynaeve, Caroline, Shah, Mitul, Smeets, Ann, Southey, Melissa C, Tollenaar, Rob A E M, Tomlinson, Ian, Tsimiklis, Helen, Ulmer, Hans-Ulrich, Vachon, Celine, van den Ouweland, Ans M W, Van't Veer, Laura J, Wildiers, Hans, Willett, Walter, Winqvist, Robert, Zamora, M Pilar, Chenevix-Trench, Georgia, Dörk, Thilo, Easton, Douglas F, García-Closas, Montserrat, Kraft, Peter, Hopper, John L, Zheng, Wei, Schmidt, Marjanka K, and Pharoah, Paul D P

Subjects
European Continental Ancestry Group, Genetic Variation, Breast Neoplasms, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Risk Assessment, Survival Analysis, Body Mass Index, Causality, Europe, Meta-Analysis as Topic, Receptors, Estrogen, Risk Factors, Mendelian randomization, breast cancer survival, Humans, epidemiology, genetics, Female, skin and connective tissue diseases
Abstract

There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer.

Published
2017

23. Common colorectal cancer risk alleles contribute to the multiple colorectal adenoma phenotype, but do not influence colonic polyposis in FAP

Author

Cheng, Timothy H. T, Gorman, Maggie, Martin, Lynn, Barclay, Ella, Casey, Graham, Newcomb, Polly A., Conti, David V., Schumacher, Fred, Gallinger, Steve, Lindor, Noralane M., Hopper, John, Jenkins, Mark, Hunter, David J., Kraft, Peter, Jacobs, Kevin B., Cox, David G., Yeager, Meredith, Hankinson, Susan E., Wacholder, Sholom, Wang, Zhaoming, Welch, Robert, Hutchinson, Amy, Wang, Junwen, Yu, Kai, Chatterjee, Nilanjan, Orr, Nick, Willett, Walter C., Colditz, Graham A., Ziegler, Regina G., Berg, Christine D., Buys, Saundra S., Mccarty, Catherine A., Feigelson, Heather Spencer, Calle, Eugenia E., Thun, Michael J., Hayes, Richard B., Tucker, Margaret, Gerhard, Daniela S., Fraumeni, Joseph F., Hoover, Robert N., Thomas, Gilles, Chanock, Stephen J., Ciampa, Julia, Gonzalez Bosquet, Jesus, Berndt, Sonja, Amundadottir, Laufey, Diver, W. Ryan, Albanes, Demetrius, Virtamo, Jarmo, Weinstein, Stephanie, Schumacher, Fredrick R., Cancel Tassin, Geraldine, Cussenot, Olivier, Valeri, Antoine, Andriole, Gerald L., Crawford, E. David, Haiman, Christopher A., Henderson, Brian, Kolonel, Laurence, Marchand, Loic Le, Siddiq, Afshan, Riboli, Elio, Key, Timothy J., Kaaks, Rudolf, Isaacs, William, Isaacs, Sarah, Wiley, Kathleen E., Gronberg, Henrik, Wiklund, Fredrik, Stattin, Pär, Xu, Jianfeng, Zheng, S. Lilly, Sun, Jielin, Vatten, Lars J., Hveem, Kristian, Kumle, Merethe, Purdue, Mark P., Johansson, Mattias, Zelenika, Diana, Toro, Jorge R., Scelo, Ghislaine, Moore, Lee E., Prokhortchouk, Egor, Wu, Xifeng, Kiemeney, Lambertus A., Gaborieau, Valerie, Chow, Wong Ho, Zaridze, David, Matveev, Vsevolod, Lubinski, Jan, Trubicka, Joanna, Szeszenia Dabrowska, Neonila, Lissowska, Jolanta, Rudnai, Péter, Fabianova, Eleonora, Bucur, Alexandru, Bencko, Vladimir, Foretova, Lenka, Janout, Vladimir, Boffetta, Paolo, Colt, Joanne S., Davis, Faith G., Schwartz, Kendra L., Banks, Rosamonde E., Selby, Peter J., Harnden, Patricia, Hsing, Ann W., Grubb, Robert L., Boeing, Heiner, Vineis, Paolo, Clavel Chapelon, Franc¸oise, Palli, Domenico, Tumino, Rosario, Krogh, Vittorio, Duell, Eric J., Quirós, José Ramón, Sanchez, Maria José, Navarro, Carmen, Ardanaz, Eva, Dorronsoro, Miren, Khaw, Kay Tee, Allen, Naomi E., Bueno de Mesquita, H. Bas, Peeters, Petra H. M., Trichopoulos, Dimitrios, Linseisen, Jakob, Ljungberg, Börje, Overvad, Kim, Tjønneland, Anne, Romieu, Isabelle, Mukeria, Anush, Shangina, Oxana, Stevens, Victoria L., Gapstur, Susan M., Pharoah, Paul D., Easton, Douglas F., Weinstein, Stephanie J., Njølstad, Inger, Tell, Grethe S., Stoltenberg, Camilla, Kumar, Rajiv, Koppova, Kvetoslava, Benhamou, Simone, Oosterwijk, Egbert, Vermeulen, Sita H., Aben, Katja K. H., Van Der Marel, Saskia L., Ye, Yuanqing, Wood, Christopher G., Pu, Xia, Mazur, Alexander M., Boulygina, Eugenia S., Chekanov, Nikolai N., Foglio, Mario, Lechner, Doris, Gut, Ivo, Heath, Simon, Blanche, Hélène, Skryabin, Konstantin G., Mckay, James D., Rothman, Nathaniel, Lathrop, Mark, Brennan, Paul, Saunders, Brian, Thomas, Huw, Clark, Sue, Tomlinson, Ian, PANICO, SALVATORE, Cheng, Timothy H. T, Gorman, Maggie, Martin, Lynn, Barclay, Ella, Casey, Graham, Newcomb, Polly A., Conti, David V., Schumacher, Fred, Gallinger, Steve, Lindor, Noralane M., Hopper, John, Jenkins, Mark, Hunter, David J., Kraft, Peter, Jacobs, Kevin B., Cox, David G., Yeager, Meredith, Hankinson, Susan E., Wacholder, Sholom, Wang, Zhaoming, Welch, Robert, Hutchinson, Amy, Wang, Junwen, Yu, Kai, Chatterjee, Nilanjan, Orr, Nick, Willett, Walter C., Colditz, Graham A., Ziegler, Regina G., Berg, Christine D., Buys, Saundra S., Mccarty, Catherine A., Feigelson, Heather Spencer, Calle, Eugenia E., Thun, Michael J., Hayes, Richard B., Tucker, Margaret, Gerhard, Daniela S., Fraumeni, Joseph F., Hoover, Robert N., Thomas, Gille, Chanock, Stephen J., Ciampa, Julia, Gonzalez Bosquet, Jesu, Berndt, Sonja, Amundadottir, Laufey, Diver, W. Ryan, Albanes, Demetriu, Virtamo, Jarmo, Weinstein, Stephanie, Schumacher, Fredrick R., Cancel Tassin, Geraldine, Cussenot, Olivier, Valeri, Antoine, Andriole, Gerald L., Crawford, E. David, Haiman, Christopher A., Henderson, Brian, Kolonel, Laurence, Marchand, Loic Le, Siddiq, Afshan, Riboli, Elio, Key, Timothy J., Kaaks, Rudolf, Isaacs, William, Isaacs, Sarah, Wiley, Kathleen E., Gronberg, Henrik, Wiklund, Fredrik, Stattin, Pär, Xu, Jianfeng, Zheng, S. Lilly, Sun, Jielin, Vatten, Lars J., Hveem, Kristian, Kumle, Merethe, Purdue, Mark P., Johansson, Mattia, Zelenika, Diana, Toro, Jorge R., Scelo, Ghislaine, Moore, Lee E., Prokhortchouk, Egor, Wu, Xifeng, Kiemeney, Lambertus A., Gaborieau, Valerie, Chow, Wong Ho, Zaridze, David, Matveev, Vsevolod, Lubinski, Jan, Trubicka, Joanna, Szeszenia Dabrowska, Neonila, Lissowska, Jolanta, Rudnai, Péter, Fabianova, Eleonora, Bucur, Alexandru, Bencko, Vladimir, Foretova, Lenka, Janout, Vladimir, Boffetta, Paolo, Colt, Joanne S., Davis, Faith G., Schwartz, Kendra L., Banks, Rosamonde E., Selby, Peter J., Harnden, Patricia, Hsing, Ann W., Grubb, Robert L., Boeing, Heiner, Vineis, Paolo, Clavel Chapelon, Franc¸oise, Palli, Domenico, Tumino, Rosario, Krogh, Vittorio, Panico, Salvatore, Duell, Eric J., Quirós, José Ramón, Sanchez, Maria José, Navarro, Carmen, Ardanaz, Eva, Dorronsoro, Miren, Khaw, Kay Tee, Allen, Naomi E., Bueno de Mesquita, H. Ba, Peeters, Petra H. M., Trichopoulos, Dimitrio, Linseisen, Jakob, Ljungberg, Börje, Overvad, Kim, Tjønneland, Anne, Romieu, Isabelle, Mukeria, Anush, Shangina, Oxana, Stevens, Victoria L., Gapstur, Susan M., Pharoah, Paul D., Easton, Douglas F., Weinstein, Stephanie J., Njølstad, Inger, Tell, Grethe S., Stoltenberg, Camilla, Kumar, Rajiv, Koppova, Kvetoslava, Benhamou, Simone, Oosterwijk, Egbert, Vermeulen, Sita H., Aben, Katja K. H., Van Der Marel, Saskia L., Ye, Yuanqing, Wood, Christopher G., Pu, Xia, Mazur, Alexander M., Boulygina, Eugenia S., Chekanov, Nikolai N., Foglio, Mario, Lechner, Dori, Gut, Ivo, Heath, Simon, Blanche, Hélène, Skryabin, Konstantin G., Mckay, James D., Rothman, Nathaniel, Lathrop, Mark, Brennan, Paul, Saunders, Brian, Thomas, Huw, Clark, Sue, and Tomlinson, Ian

Subjects
Adenoma, Allele, Male, Genes, Modifier, Adenomatous Polyposis Coli Protein, Colorectal Neoplasm, Middle Aged, Polymorphism, Single Nucleotide, Phenotype, Adenomatous Polyposis Coli, Genetics, Female, Genetic Predisposition to Disease, DNA Glycosylase, Germ-Line Mutation, Genetics (clinical), Aged, Human
Abstract

The presence of multiple (5-100) colorectal adenomas suggests an inherited predisposition, but the genetic aetiology of this phenotype is undetermined if patients test negative for Mendelian polyposis syndromes such as familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP). We investigated whether 18 common colorectal cancer (CRC) predisposition single-nucleotide polymorphisms (SNPs) could help to explain some cases with multiple adenomas who phenocopied FAP or MAP, but had no pathogenic APC or MUTYH variant. No multiple adenoma case had an outlying number of CRC SNP risk alleles, but multiple adenoma patients did have a significantly higher number of risk alleles than population controls (P=5.7 × 10(-7)). The association was stronger in those with ≥10 adenomas. The CRC SNPs accounted for 4.3% of the variation in multiple adenoma risk, with three SNPs (rs6983267, rs10795668, rs3802842) explaining 3.0% of the variation. In FAP patients, the CRC risk score did not differ significantly from the controls, as we expected given the overwhelming effect of pathogenic germline APC variants on the phenotype of these cases. More unexpectedly, we found no evidence that the CRC SNPs act as modifier genes for the number of colorectal adenomas in FAP patients. In conclusion, common colorectal tumour risk alleles contribute to the development of multiple adenomas in patients without pathogenic germline APC or MUTYH variants. This phenotype may have 'polygenic' or monogenic origins. The risk of CRC in relatives of multiple adenoma cases is probably much lower for cases with polygenic disease, and this should be taken into account when counselling such patients.

Published
2015

24. Genome-wide association study of susceptibility loci for breast cancer in Sardinian population

Author

Palomba, Grazia, Loi, Angela, Porcu, Eleonora, Cossu, Antonio, Zara, Ilenia, Budroni, Mario, Dei, Mariano, Lai, Sandra, Mulas, Antonella, Olmeo, Nina, Ionta, Maria Teresa, Atzori, Francesco, Cuccuru, Gianmauro, Pitzalis, Maristella, Zoledziewska, Magdalena, Olla, Nazario, Lovicu, Mario, Pisano, Marina, Abecasis, Gonçalo R, Uda, Manuela, Tanda, Francesco, Michailidou, Kyriaki, Easton, Douglas F, Chanock, Stephen J, Hoover, Robert N, Hunter, David J, Schlessinger, David, Sanna, Serena, Crisponi, Laura, and Palmieri, Giuseppe

Subjects
Genes, BRCA2, Genes, BRCA1, High Mobility Group Proteins, Breast Neoplasms, Penetrance, Polymorphism, Single Nucleotide, Italy, Genetic Loci, Case-Control Studies, Trans-Activators, Humans, Female, Genetic Predisposition to Disease, Receptor, Fibroblast Growth Factor, Type 2, Apoptosis Regulatory Proteins, Receptors, Progesterone, Genome-Wide Association Study
Abstract

BACKGROUND: Despite progress in identifying genes associated with breast cancer, many more risk loci exist. Genome-wide association analyses in genetically-homogeneous populations, such as that of Sardinia (Italy), could represent an additional approach to detect low penetrance alleles. METHODS: We performed a genome-wide association study comparing 1431 Sardinian patients with non-familial, BRCA1/2-mutation-negative breast cancer to 2171 healthy Sardinian blood donors. DNA was genotyped using GeneChip Human Mapping 500 K Arrays or Genome-Wide Human SNP Arrays 6.0. To increase genomic coverage, genotypes of additional SNPs were imputed using data from HapMap Phase II. After quality control filtering of genotype data, 1367 cases (9 men) and 1658 controls (1156 men) were analyzed on a total of 2,067,645 SNPs. RESULTS: Overall, 33 genomic regions (67 candidate SNPs) were associated with breast cancer risk at the p < 0(-6) level. Twenty of these regions contained defined genes, including one already associated with breast cancer risk: TOX3. With a lower threshold for preliminary significance to p < 10(-5), we identified 11 additional SNPs in FGFR2, a well-established breast cancer-associated gene. Ten candidate SNPs were selected, excluding those already associated with breast cancer, for technical validation as well as replication in 1668 samples from the same population. Only SNP rs345299, located in intron 1 of VAV3, remained suggestively associated (p-value, 1.16 x 10(-5)), but it did not associate with breast cancer risk in pooled data from two large, mixed-population cohorts. CONCLUSIONS: This study indicated the role of TOX3 and FGFR2 as breast cancer susceptibility genes in BRCA1/2-wild-type breast cancer patients from Sardinian population.

Published
2016
Full Text
View/download PDF

25. Analysis of heritability and shared heritability based on Genome-Wide Association Studies for 13 Cancer Types

Author

Sampson, Joshua N., Wheeler, William A., Yeager, Meredith, Panagiotou, Orestis, Wang, Zhaoming, Berndt, Sonja I., Lan, Qing, Abnet, Christian C., Amundadottir, Laufey T., Figueroa, Jonine D., Landi, Maria Teresa, Mirabello, Lisa, Savage, Sharon A., Taylor, Philip R., Vivo, Immaculata De, McGlynn, Katherine A., Purdue, Mark P., Rajaraman, Preetha, Adami, Hans-Olov, Ahlbom, Anders, Albanes, Demetrius, Amary, Maria Fernanda, An, She-Juan, Andersson, Ulrika, Andriole, Gerald, Andrulis, Irene L., Angelucci, Emanuele, Ansell, Stephen M., Arici, Cecilia, Armstrong, Bruce K., Arslan, Alan A., Austin, Melissa A., Baris, Dalsu, Barkauskas, Donald A., Bassig, Bryan A., Becker, Nikolaus, Benavente, Yolanda, Benhamou, Simone, Berg, Christine, Van Den Berg, David, Bernstein, Leslie, Bertrand, Kimberly A., Birmann, Brenda M., Black, Amanda, Boeing, Heiner, Boffetta, Paolo, Boutron-Ruault, Marie-Christine, Bracci, Paige M., Brinton, Louise, Brooks-Wilson, Angela R., Bueno-de-Mesquita, H. Bas, Burdett, Laurie, Buring, Julie, Butler, Mary Ann, Cai, Qiuyin, Cancel-Tassin, Geraldine, Canzian, Federico, Carrato, Alfredo, Carreon, Tania, Carta, Angela, Chan, John K. C., Chang, Ellen T., Chang, Gee-Chen, Chang, I-Shou, Chang, Jiang, Chang-Claude, Jenny, Chen, Chien-Jen, Chen, Chih-Yi, Chen, Chu, Chen, Chung-Hsing, Chen, Constance, Chen, Hongyan, Chen, Kexin, Chen, Kuan-Yu, Chen, Kun-Chieh, Chen, Ying, Chen, Ying-Hsiang, Chen, Yi-Song, Chen, Yuh-Min, Chien, Li-Hsin, Chirlaque, María-Dolores, Choi, Jin Eun, Choi, Yi Young, Chow, Wong-Ho, Chung, Charles C., Clavel, Jacqueline, Clavel-Chapelon, Françoise, Cocco, Pierluigi, Colt, Joanne S., Comperat, Eva, Conde, Lucia, Connors, Joseph M., Conti, David, Cortessis, Victoria K., Cotterchio, Michelle, Cozen, Wendy, Crouch, Simon, Crous-Bou, Marta, Cussenot, Olivier, Davis, Faith G., Ding, Ti, Diver, W. Ryan, Dorronsoro, Miren, Dossus, Laure, Duell, Eric J., Ennas, Maria Grazia, Erickson, Ralph L., Feychting, Maria, Flanagan, Adrienne M., Foretova, Lenka, Fraumeni, Joseph F., Freedman, Neal D., Beane Freeman, Laura E., Fuchs, Charles, Gago-Dominguez, Manuela, Gallinger, Steven, Gao, Yu-Tang, Gapstur, Susan M., Garcia-Closas, Montserrat, García-Closas, Reina, Gascoyne, Randy D., Gastier-Foster, Julie, Gaudet, Mia M., Gaziano, J. Michael, Giffen, Carol, Giles, Graham G., Giovannucci, Edward, Glimelius, Bengt, Goggins, Michael, Gokgoz, Nalan, Goldstein, Alisa M., Gorlick, Richard, Gross, Myron, Grubb, Robert, Gu, Jian, Guan, Peng, Gunter, Marc, Guo, Huan, Habermann, Thomas M., Haiman, Christopher A., Halai, Dina, Hallmans, Goran, Hassan, Manal, Hattinger, Claudia, He, Qincheng, He, Xingzhou, Helzlsouer, Kathy, Henderson, Brian, Henriksson, Roger, Hjalgrim, Henrik, Hoffman-Bolton, Judith, Hohensee, Chancellor, Holford, Theodore R., Holly, Elizabeth A., Hong, Yun-Chul, Hoover, Robert N., Horn-Ross, Pamela L., Hosain, G. M. Monawar, Hosgood, H. Dean, Hsiao, Chin-Fu, Hu, Nan, Hu, Wei, Hu, Zhibin, Huang, Ming-Shyan, Huerta, Jose-Maria, Hung, Jen-Yu, Hutchinson, Amy, Inskip, Peter D., Jackson, Rebecca D., Jacobs, Eric J., Jenab, Mazda, Jeon, Hyo-Sung, Ji, Bu-Tian, Jin, Guangfu, Jin, Li, Johansen, Christoffer, Johnson, Alison, Jung, Yoo Jin, Kaaks, Rudolph, Kamineni, Aruna, Kane, Eleanor, Kang, Chang Hyun, Karagas, Margaret R., Kelly, Rachel S., Khaw, Kay-Tee, Kim, Christopher, Kim, Hee Nam, Kim, Jin Hee, Kim, Jun Suk, Kim, Yeul Hong, Kim, Young Tae, Kim, Young-Chul, Kitahara, Cari M., Klein, Alison P., Klein, Robert J., Kogevinas, Manolis, Kohno, Takashi, Kolonel, Laurence N., Kooperberg, Charles, Kricker, Anne, Krogh, Vittorio, Kunitoh, Hideo, Kurtz, Robert C., Kweon, Sun-Seog, LaCroix, Andrea, Lawrence, Charles, Lecanda, Fernando, Lee, Victor Ho Fun, Li, Donghui, Li, Haixin, Li, Jihua, Li, Yao-Jen, Li, Yuqing, Liao, Linda M., Liebow, Mark, Lightfoot, Tracy, Lim, Wei-Yen, Lin, Chien-Chung, Lin, Dongxin, Lindstrom, Sara, Linet, Martha S., Link, Brian K., Liu, Chenwei, Liu, Jianjun, Liu, Li, Ljungberg, Börje, Lloreta, Josep, Lollo, Simonetta Di, Lu, Daru, Lund, Eiluv, Malats, Nuria, Mannisto, Satu, Marchand, Loic Le, Marina, Neyssa, Masala, Giovanna, Mastrangelo, Giuseppe, Matsuo, Keitaro, Maynadie, Marc, McKay, James, McKean-Cowdin, Roberta, Melbye, Mads, Melin, Beatrice S., Michaud, Dominique S., Mitsudomi, Tetsuya, Monnereau, Alain, Montalvan, Rebecca, Moore, Lee E., Mortensen, Lotte Maxild, Nieters, Alexandra, North, Kari E., Novak, Anne J., Oberg, Ann L., Offit, Kenneth, Oh, In-Jae, Olson, Sara H., Palli, Domenico, Pao, William, Park, In Kyu, Park, Jae Yong, Park, Kyong Hwa, Patiño-Garcia, Ana, Pavanello, Sofia, Peeters, Petra H. M., Perng, Reury-Perng, Peters, Ulrike, Petersen, Gloria M., Picci, Piero, Pike, Malcolm C., Porru, Stefano, Prescott, Jennifer, Prokunina-Olsson, Ludmila, Qian, Biyun, Qiao, You-Lin, Rais, Marco, Riboli, Elio, Riby, Jacques, Risch, Harvey A., Rizzato, Cosmeri, Rodabough, Rebecca, Roman, Eve, Roupret, Morgan, Ruder, Avima M., de Sanjose, Silvia, Scelo, Ghislaine, Schned, Alan, Schumacher, Fredrick, Schwartz, Kendra, Schwenn, Molly, Scotlandi, Katia, Seow, Adeline, Serra, Consol, Serra, Massimo, Sesso, Howard D., Setiawan, Veronica Wendy, Severi, Gianluca, Severson, Richard K., Shanafelt, Tait D., Shen, Hongbing, Shen, Wei, Shin, Min-Ho, Shiraishi, Kouya, Shu, Xiao-Ou, Siddiq, Afshan, Sierrasesúmaga, Luis, Sihoe, Alan Dart Loon, Skibola, Christine F., Smith, Alex, Smith, Martyn T., Southey, Melissa C., Spinelli, John J., Staines, Anthony, Stampfer, Meir, Stern, Marianna C., Stevens, Victoria L., Stolzenberg-Solomon, Rachael S., Su, Jian, Su, Wu-Chou, Sund, Malin, Sung, Jae Sook, Sung, Sook Whan, Tan, Wen, Tang, Wei, Tardón, Adonina, Thomas, David, Thompson, Carrie A., Tinker, Lesley F., Tirabosco, Roberto, Tjønneland, Anne, Travis, Ruth C., Trichopoulos, Dimitrios, Tsai, Fang-Yu, Tsai, Ying-Huang, Tucker, Margaret, Turner, Jenny, Vajdic, Claire M., Vermeulen, Roel C. H., Villano, Danylo J., Vineis, Paolo, Virtamo, Jarmo, Visvanathan, Kala, Wactawski-Wende, Jean, Wang, Chaoyu, Wang, Chih-Liang, Wang, Jiu-Cun, Wang, Junwen, Wei, Fusheng, Weiderpass, Elisabete, Weiner, George J., Weinstein, Stephanie, Wentzensen, Nicolas, White, Emily, Witzig, Thomas E., Wolpin, Brian M., Wong, Maria Pik, Wu, Chen, Wu, Guoping, Wu, Junjie, Wu, Tangchun, Wu, Wei, Wu, Xifeng, Wu, Yi-Long, Wunder, Jay S., Xiang, Yong-Bing, Xu, Jun, Xu, Ping, Yang, Pan-Chyr, Yang, Tsung-Ying, Ye, Yuanqing, Yin, Zhihua, Yokota, Jun, Yoon, Ho-Il, Yu, Chong-Jen, Yu, Herbert, Yu, Kai, Yuan, Jian-Min, Zelenetz, Andrew, Zeleniuch-Jacquotte, Anne, Zhang, Xu-Chao, Zhang, Yawei, Zhao, Xueying, Zhao, Zhenhong, Zheng, Hong, Zheng, Tongzhang, Zheng, Wei, Zhou, Baosen, Zhu, Meng, Zucca, Mariagrazia, Boca, Simina M., Cerhan, James R., Ferri, Giovanni M., Hartge, Patricia, Hsiung, Chao Agnes, Magnani, Corrado, Miligi, Lucia, Morton, Lindsay M., Smedby, Karin E., Teras, Lauren R., Vijai, Joseph, Wang, Sophia S., Brennan, Paul, Caporaso, Neil E., Hunter, David J., Kraft, Peter, Rothman, Nathaniel, Silverman, Debra T., Slager, Susan L., Chanock, Stephen J., and Chatterjee, Nilanjan

Subjects
Adult, Asian Continental Ancestry Group, Male, Lung Neoplasms, DATABASE, European Continental Ancestry Group, RELATIVES, Bone Neoplasms, Polymorphism, Single Nucleotide, Article, LUNG-CANCER, Testicular Neoplasms, Neoplasms, SWEDEN, LYMPHOMA, Humans, Genetic Predisposition to Disease, FAMILIAL RISK, Oncology & Carcinogenesis, Aged, Osteosarcoma, Science & Technology, MUTATIONS, Smoking, Middle Aged, Leukemia, Lymphocytic, Chronic, B-Cell, PANCREATIC-CANCER, Kidney Neoplasms, MULTIPLE SUSCEPTIBILITY LOCI, INDIVIDUALS, Oncology, Urinary Bladder Neoplasms, Tissue Array Analysis, Female, Lymphoma, Large B-Cell, Diffuse, Life Sciences & Biomedicine, 1112 Oncology And Carcinogenesis, Genome-Wide Association Study
Abstract

Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common SNPs for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49,492 cancer cases and 34,131 controls. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl2, on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% CI = 14% - 37%) and 7% (4% - 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ=0.73, SE=0.28), Diffuse Large B-Cell Lymphoma (DLBCL) and pediatric osteosarcoma (ρ=0.53, SE=0.21), DLBCL and Chronic Lymphocytic Leukemia (CLL) (ρ=0.51, SE=0.18), and bladder and lung (ρ=0.35, SE=0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a non-smoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.

Published
2015

26. Genome-wide association study of susceptibility loci for breast cancer in Sardinian population

Author

Palomba, Grazia, Loi, Angela, Porcu, Eleonora, Cossu, Antonio, Zara, Ilenia, Budroni, Mario, Dei, Mariano, Lai, Sandra, Mulas, Antonella, Olmeo, Nina, Ionta, Maria Teresa, Atzori, Francesco, Cuccuru, Gianmauro, Pitzalis, Maristella, Zoledziewska, Magdalena, Olla, Nazario, Lovicu, Mario, Pisano, Marina, Abecasis, Gonçalo R, Uda, Manuela, Tanda, Francesco, Michailidou, Kyriaki, Easton, Douglas F, Chanock, Stephen J, Hoover, Robert N, Hunter, David J, Schlessinger, David, Sanna, Serena, Crisponi, Laura, Palmieri, Giuseppe, and Apollo - University of Cambridge Repository

Subjects
Genes, BRCA2, Genes, BRCA1, High Mobility Group Proteins, Breast Neoplasms, Penetrance, Polymorphism, Single Nucleotide, Italy, Genetic Loci, Case-Control Studies, Trans-Activators, Humans, Female, Genetic Predisposition to Disease, Receptor, Fibroblast Growth Factor, Type 2, Apoptosis Regulatory Proteins, Receptors, Progesterone, Genome-Wide Association Study
Abstract

BACKGROUND: Despite progress in identifying genes associated with breast cancer, many more risk loci exist. Genome-wide association analyses in genetically-homogeneous populations, such as that of Sardinia (Italy), could represent an additional approach to detect low penetrance alleles. METHODS: We performed a genome-wide association study comparing 1431 Sardinian patients with non-familial, BRCA1/2-mutation-negative breast cancer to 2171 healthy Sardinian blood donors. DNA was genotyped using GeneChip Human Mapping 500 K Arrays or Genome-Wide Human SNP Arrays 6.0. To increase genomic coverage, genotypes of additional SNPs were imputed using data from HapMap Phase II. After quality control filtering of genotype data, 1367 cases (9 men) and 1658 controls (1156 men) were analyzed on a total of 2,067,645 SNPs. RESULTS: Overall, 33 genomic regions (67 candidate SNPs) were associated with breast cancer risk at the p

Published
2015

27. Common germline polymorphisms associated with breast cancer-specific survival

Author

Pirie, Ailith, Guo, Qi, Kraft, Peter, Canisius, Sander, Eccles, Diana M, Rahman, Nazneen, Nevanlinna, Heli, Chen, Constance, Khan, Sofia, Tyrer, Jonathan, Bolla, Manjeet K, Wang, Qin, Dennis, Joe, Michailidou, Kyriaki, Lush, Michael, Dunning, Alison M, Shah, Mitul, Czene, Kamila, Darabi, Hatef, Eriksson, Mikael, Lambrechts, Dieter, Weltens, Caroline, Leunen, Karin, van Ongeval, Chantal, Nordestgaard, Børge G, Nielsen, Sune F, Flyger, Henrik, Rudolph, Anja, Seibold, Petra, Flesch-Janys, Dieter, Blomqvist, Carl, Aittomäki, Kristiina, Fagerholm, Rainer, Muranen, Taru A, Olsen, Janet E, Hallberg, Emily, Vachon, Celine, Knight, Julia A, Glendon, Gord, Mulligan, Anna Marie, Broeks, Annegien, Cornelissen, Sten, Haiman, Christopher A, Henderson, Brian E, Schumacher, Frederick, Le Marchand, Loic, Hopper, John L, Tsimiklis, Helen, Apicella, Carmel, Southey, Melissa C, Cross, Simon S, Reed, Malcolm Wr, Giles, Graham G, Milne, Roger L, McLean, Catriona, Winqvist, Robert, Pylkäs, Katri, Jukkola-Vuorinen, Arja, Grip, Mervi, Hooning, Maartje J, Hollestelle, Antoinette, Martens, John Wm, van den Ouweland, Ans Mw, Marme, Federick, Schneeweiss, Andreas, Yang, Rongxi, Burwinkel, Barbara, Figueroa, Jonine, Chanock, Stephen J, Lissowska, Jolanta, Sawyer, Elinor J, Tomlinson, Ian, Kerin, Michael J, Miller, Nicola, Brenner, Hermann, Butterbach, Katja, Holleczek, Bernd, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana M, Li, Jingmei, Brand, Judith S, Humphreys, Keith, Devilee, Peter, Tollenaar, Robert Aem, Seynaeve, Caroline, Radice, Paolo, Peterlongo, Paolo, Manoukian, Siranoush, Ficarazzi, Filomena, Beckmann, Matthias W, Hein, Alexander, Ekici, Arif B, Balleine, Rosemary, Phillips, Kelly-Anne, kConFab Investigators, Benitez, Javier, Zamora, M Pilar, Perez, Jose Ignacio Arias, Menéndez, Primitiva, Jakubowska, Anna, Lubinski, Jan, Gronwald, Jacek, Durda, Katarzyna, Hamann, Ute, Kabisch, Maria, Ulmer, Hans Ulrich, Rüdiger, Thomas, Margolin, Sara, Kristensen, Vessela, Nord, Siljie, NBCS Investigators, Evans, D Gareth, Abraham, Jean, Earl, Helena, Poole, Christopher J, Hiller, Louise, Dunn, Janet A, Bowden, Sarah, Yang, Rose, Campa, Daniele, Diver, W Ryan, Gapstur, Susan M, Gaudet, Mia M, Hankinson, Susan, Hoover, Robert N, Hüsing, Anika, Kaaks, Rudolf, Machiela, Mitchell J, Willett, Walter, Barrdahl, Myrto, Canzian, Federico, Chin, Suet-Feung, Caldas, Carlos, Hunter, David J, Lindstrom, Sara, Garcia-Closas, Montserrat, Couch, Fergus J, Chenevix-Trench, Georgia, Mannermaa, Arto, Andrulis, Irene L, Hall, Per, Chang-Claude, Jenny, Easton, Douglas F, Bojesen, Stig E, Cox, Angela, Fasching, Peter A, Pharoah, Paul Dp, Schmidt, Marjanka K, Tyrer, Jonathan [0000-0003-3724-4757], Wang, Jean [0000-0002-9139-0627], Dennis, Joe [0000-0003-4591-1214], Dunning, Alison [0000-0001-6651-7166], Abraham, Jean [0000-0003-0688-4807], Earl, Helena [0000-0003-1549-8094], Chin, Suet-Feung [0000-0001-5697-1082], Caldas, Carlos [0000-0003-3547-1489], Easton, Douglas [0000-0003-2444-3247], Pharoah, Paul [0000-0001-8494-732X], Apollo - University of Cambridge Repository, Obstetrics & Gynecology, Clinical Genetics, and Medical Oncology

Subjects
PROGNOSIS, SINGLE-NUCLEOTIDE POLYMORPHISMS, GENOME-WIDE ASSOCIATION, THAN-T POLYMORPHISM, GENETIC POLYMORPHISMS, ADJUVANT THERAPY, RISK, OUTCOMES, VARIANTS, GENOTYPE, Breast Neoplasms, Polymorphism, Single Nucleotide, RC0254, SDG 3 - Good Health and Well-being, Medizinische Fakultät, Humans, Genetic Predisposition to Disease, ddc:610, skin and connective tissue diseases, Genetic Association Studies, Medicine(all), Prognosis, Germ Cells, Female, Genome-Wide Association Study, Research Article
Abstract

Introduction Previous studies have identified common germline variants nominally associated with breast cancer survival. These associations have not been widely replicated in further studies. The purpose of this study was to evaluate the association of previously reported SNPs with breast cancer-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium. Methods A literature review was conducted of all previously published associations between common germline variants and three survival outcomes: breast cancer-specific survival, overall survival and disease-free survival. All associations that reached the nominal significance level of P value

Published
2015

28. Factors associated with oxidative stress and cancer risk in the Breast and Prostate Cancer Cohort Consortium (BPC3)

Author

Blein, Sophie, Berndt, Sonja, Joshi, Amit D., Campa, Daniele, Ziegler, Regina G., Riboli, Elio, Cox, David G., Gaudet, Mia M., Stevens, Victoria L., Diver, W. Ryan, Gapstur, Susan M., Chanock, Stephen J., Hoover, Robert N., Yeager, Meredith, Albanes, Demetrius, Virtamo, Jarmo, Crawford, E. David, Isaacs, Claudine, Berg, Christine, Trichopoulos, Dimitrios, Panico, Salvatore, Peeters, Petra H., Johansson, Mattias, Khaw, Kay-Tee, Kraft, Peter, Hunter, David J., Lindström, Sara, Ma, Jing, Stampfer, Meir, Gaziano, J. Michael, Giovannucci, Edward, Willett, Walter H., Hankinson, Susan E., Lee, I-Min, Buring, Julie, Henderson, Brian, Le Marchand, Loïc, Kolonel, Laurence, and Haiman, Christopher J.

Subjects
Male, Oxidative Stress, Genotype, Humans, Prostatic Neoplasms, Breast Neoplasms, Female, Genetic Predisposition to Disease, Reactive Oxygen Species, Polymorphism, Single Nucleotide, Survival Analysis, Article
Abstract

Both endogenous factors (genomic variations) and exogenous factors (environmental exposures, lifestyle) impact the balance of reactive oxygen species (ROS). Variants of the ND3 (rs2853826; G10398A) gene of the mitochondrial genome, manganese superoxide dismutase (MnSOD; rs4880 Val16Ala) and glutathione peroxidase (GPX-1; rs1050450 Pro198Leu) are purported to have functional effects on regulation of ROS balance. In this study, we examined associations of breast and prostate cancer risk and survival with these variants, and interactions between rs4880 - rs1050450 and alcohol consumption - rs2853826. Nested case-control studies were conducted in the Breast and Prostate Cancer Cohort Consortium (BPC3), consisting of nine cohorts. The analyses included over 10726 post-menopausal breast and 7532 prostate cancer cases with matched controls. Logistic regression models were used to evaluate associations with risk, and proportional hazard models were used for survival outcomes. We did not observe significant interactions between polymorphisms in MnSOD and GPX-1, or between mitochondrial polymorphisms and alcohol intake and risk of either breast (p-interaction of 0.34 and 0.98 respectively) or prostate cancer (p-interaction of 0.49 and 0.50 respectively). We observed a weak inverse association between prostate cancer risk and GPX-1 Leu198Leu carriers (OR 0.87, 95% CI 0.79 – 0.97, p = 0.01). Overall survival among women with breast cancer was inversely associated with G10398 carriers who consumed alcohol (HR 0.66 95% CI 0.49 – 0.88). Given the high power in our study, it is unlikely that interactions tested have more than moderate effects on breast or prostate cancer risk. Observed associations need both further epidemiological and biological confirmation.

Published
2014

29. Additive interactions between susceptibility single-nucleotide polymorphisms identified in genome-wide association studies and breast cancer risk factors in the Breast and Prostate Cancer Cohort Consortium

Author

Joshi, Amit D., Lindström, Sara, Hüsing, Anika, Barrdahl, Myrto, VanderWeele, Tyler J., Campa, Daniele, Canzian, Federico, Gaudet, Mia M., Figueroa, Jonine D., Baglietto, Laura, Berg, Christine D., Buring, Julie E., Chanock, Stephen J., Chirlaque, María-Dolores, Diver, W. Ryan, Dossus, Laure, Giles, Graham G., Haiman, Christopher A., Hankinson, Susan E., Henderson, Brian E., Hoover, Robert N., Hunter, David J., Isaacs, Claudine, Kaaks, Rudolf, Kolonel, Laurence N., Krogh, Vittorio, Le Marchand, Loic, Lee, I-Min, Lund, Eiliv, McCarty, Catherine A., Overvad, Kim, Peeters, Petra H., Riboli, Elio, Schumacher, Fredrick, Severi, Gianluca, Stram, Daniel O., Sund, Malin, Thun, Michael J., Travis, Ruth C., Trichopoulos, Dimitrios, Willett, Walter C., Zhang, Shumin, Ziegler, Regina G., Kraft, Peter, and Marchand, Loic Le

Subjects
Male, Oncology, medicine.medical_specialty, Pathology, Epidemiology, Original Contributions, Additive interactions, Breast cancer, Genome-wide association studies, Single-nucleotide polymorphisms, Breast Neoplasms, Single-nucleotide polymorphism, Genome-wide association study, Polymorphism, Single Nucleotide, Risk Assessment, White People, Body Mass Index, Cohort Studies, Prostate cancer, Risk Factors, Internal medicine, Biomarkers, Tumor, Odds Ratio, Humans, Medicine, Genetic Predisposition to Disease, Alleles, business.industry, Australia, Absolute risk reduction, Case-control study, Prostatic Neoplasms, Odds ratio, Middle Aged, medicine.disease, United States, DNA-Binding Proteins, Europe, Case-Control Studies, Female, Rad51 Recombinase, business, Risk assessment, Genome-Wide Association Study
Abstract

Additive interactions can have public health and etiological implications but are infrequently reported. We assessed departures from additivity on the absolute risk scale between 9 established breast cancer risk factors and 23 susceptibility single-nucleotide polymorphisms (SNPs) identified from genome-wide association studies among 10,146 non-Hispanic white breast cancer cases and 12,760 controls within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium. We estimated the relative excess risk due to interaction and its 95% confidence interval for each pairwise combination of SNPs and nongenetic risk factors using age- and cohort-adjusted logistic regression models. After correction for multiple comparisons, we identified a statistically significant relative excess risk due to interaction (uncorrected P = 4.51 × 10(-5)) between a SNP in the DNA repair protein RAD51 homolog 2 gene (RAD51L1; rs10483813) and body mass index (weight (kg)/height (m)(2)). We also compared additive and multiplicative polygenic risk prediction models using per-allele odds ratio estimates from previous studies for breast-cancer susceptibility SNPs and observed that the multiplicative model had a substantially better goodness of fit than the additive model.

Published
2014

30. Comparison of liquid chromatography-mass spectrometry, radioimmunoassay, and enzyme-linked immunosorbent assay methods for measurement of urinary estrogens

Author

Faupel-Badger, Jessica M., Fuhrman, Barbara J., Xu, Xia, Falk, Roni T., Keefer, Larry K., Veenstra, Timothy D., Hoover, Robert N., and Ziegler, Regina G.

Subjects
Adult, Postmenopause, Asian, Premenopause, Tandem Mass Spectrometry, Radioimmunoassay, Humans, Enzyme-Linked Immunosorbent Assay, Estrogens, Female, Middle Aged, Article, Chromatography, Liquid
Abstract

Absolute and relative concentrations of estrogens and estrogen metabolites are important for clinical decisions as well as for epidemiologic, experimental, and clinical research on hormonal carcinogenesis. RIA and ELISA are routinely used for measuring estrogen metabolites in blood and urine due to efficiency and low cost. Here, we compare absolute and ranked concentrations of estrone, estradiol, and estriol measured by indirect RIA and of 2-hydroxyestrone and 16alpha-hydroxyestrone measured by ELISA to the concentrations obtained using a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, which measures 15 estrogen metabolites concurrently. We used overnight urine samples collected from control women (362 premenopausal and 168 postmenopausal) participating in a population-based case-control study of breast cancer among Asian American women ages 20 to 55 years. When comparing RIA or ELISA levels to LC-MS/MS, absolute concentrations for the five estrogen metabolites ranged from 1.6 to 2.9 and 1.4 to 11.8 times higher in premenopausal and postmenopausal women, respectively (all P0.0001). However, LC-MS/MS measurements were highly correlated [Spearman r (r(s)) = 0.8-0.9] with RIA and ELISA measurements in premenopausal women and moderately correlated (r(s) = 0.4-0.8) in postmenopausal women. Measurements of the 2-hydroxyestrone:16alpha-hydroxyestrone ratio, a putative biomarker of breast cancer risk, were moderately correlated in premenopausal women (r(s) = 0.6-0.7) but only weakly correlated in postmenopausal women (r(s) = 0.2). LC-MS/MS had higher intraclass correlation coefficients (or =99.6%) and lower coefficients of variation (or =9.4%) than ELISA (or =97.2% andor =14.2%) and RIA (or =95.2% andor =17.8%). Comparison with the LC-MS/MS method suggests that the widely used RIA and ELISA estrogen metabolite measures may be problematic, especially at low estrogen metabolite levels characteristic of postmenopausal women.

Published
2010

31. Transcriptome-wide association study of breast cancer risk by estrogen-receptor status

Author

Feng, Helian, Gusev, Alexander, Pasaniuc, Bogdan, Wu, Lang, Long, Jirong, Abu-Full, Zomoroda, Aittomäki, Kristiina, Andrulis, Irene L, Anton-Culver, Hoda, Antoniou, Antonis C, Arason, Adalgeir, Arndt, Volker, Aronson, Kristan J, Arun, Banu K, Asseryanis, Ella, Auer, Paul L, Azzollini, Jacopo, Balmaña, Judith, Barkardottir, Rosa B, Barnes, Daniel R, Barrowdale, Daniel, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Białkowska, Katarzyna, Blanco, Ana, Blomqvist, Carl, Boeckx, Bram, Bogdanova, Natalia V, Bojesen, Stig E, Bolla, Manjeet K, Bonanni, Bernardo, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Briceno, Ignacio, Broeks, Annegien, Brüning, Thomas, Burwinkel, Barbara, Cai, Qiuyin, Caldés, Trinidad, Caligo, Maria A, Campbell, Ian, Canisius, Sander, Campa, Daniele, Carter, Brian D, Carter, Jonathan, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Christiansen, Hans, Chung, Wendy K, Claes, Kathleen BM, Clarke, Christine L, GEMO Study Collaborators, EMBRACE Collaborators, GC-HBOC Study Collaborators, Couch, Fergus J, Cox, Angela, Cross, Simon S, Cybulski, Cezary, Czene, Kamila, Daly, Mary B, De La Hoya, Miguel, De Leeneer, Kim, Dennis, Joe, Devilee, Peter, Diez, Orland, Domchek, Susan M, Dörk, Thilo, Dos-Santos-Silva, Isabel, Dunning, Alison M, Dwek, Miriam, Eccles, Diana M, Ejlertsen, Bent, Ellberg, Carolina, Engel, Christoph, Eriksson, Mikael, Fasching, Peter A, Fletcher, Olivia, Flyger, Henrik, Fostira, Florentia, Friedman, Eitan, Fritschi, Lin, Frost, Debra, Gabrielson, Marike, Ganz, Patricia A, Gapstur, Susan M, Garber, Judy, García-Closas, Montserrat, García-Sáenz, José A, Gaudet, Mia M, Giles, Graham G, Glendon, Gord, Godwin, Andrew K, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Greene, Mark H, Gronwald, Jacek, Guénel, Pascal, Haiman, Christopher A, Hall, Per, Hamann, Ute, Hake, Christopher, He, Wei, Heyworth, Jane, Hogervorst, Frans BL, Hollestelle, Antoinette, Hooning, Maartje J, Hoover, Robert N, Hopper, John L, Huang, Guanmengqian, Hulick, Peter J, Humphreys, Keith, Imyanitov, Evgeny N, ABCTB Investigators, HEBON Investigators, BCFR Investigators, OCGN Investigators, Isaacs, Claudine, Jakimovska, Milena, Jakubowska, Anna, James, Paul, Janavicius, Ramunas, Jankowitz, Rachel C, John, Esther M, Johnson, Nichola, Joseph, Vijai, Jung, Audrey, Karlan, Beth Y, Khusnutdinova, Elza, Kiiski, Johanna I, Konstantopoulou, Irene, Kristensen, Vessela N, Laitman, Yael, Lambrechts, Diether, Lazaro, Conxi, Leroux, Dominique, Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Lindor, Noralane, Lindström, Sara, Lo, Wing-Yee, Loud, Jennifer T, Lubiński, Jan, Makalic, Enes, Mannermaa, Arto, Manoochehri, Mehdi, Manoukian, Siranoush, Margolin, Sara, Martens, John WM, Martinez, Maria E, Matricardi, Laura, Maurer, Tabea, Mavroudis, Dimitrios, McGuffog, Lesley, Meindl, Alfons, Menon, Usha, Michailidou, Kyriaki, Kapoor, Pooja M, Miller, Austin, Montagna, Marco, Moreno, Fernando, Moserle, Lidia, Mulligan, Anna M, Muranen, Taru A, Nathanson, Katherine L, Neuhausen, Susan L, Nevanlinna, Heli, Nevelsteen, Ines, Nielsen, Finn C, Nikitina-Zake, Liene, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I, Olsson, Håkan, Osorio, Ana, Papp, Janos, Park-Simon, Tjoung-Won, Parsons, Michael T, Pedersen, Inge S, Peixoto, Ana, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul DP, Phillips, Kelly-Anne, Plaseska-Karanfilska, Dijana, Poppe, Bruce, Pradhan, Nisha, Prajzendanc, Karolina, Presneau, Nadege, Punie, Kevin, Pylkäs, Katri, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad Usman, Rennert, Gad, Risch, Harvey A, Robson, Mark, Romero, Atocha, Saloustros, Emmanouil, Sandler, Dale P, Santos, Catarina, Sawyer, Elinor J, Schmidt, Marjanka K, Schmidt, Daniel F, Schmutzler, Rita K, Schoemaker, Minouk J, Scott, Rodney J, Sharma, Priyanka, Shu, Xiao-Ou, Simard, Jacques, Singer, Christian F, Skytte, Anne-Bine, Soucy, Penny, Southey, Melissa C, Spinelli, John J, Spurdle, Amanda B, Stone, Jennifer, Swerdlow, Anthony J, Tapper, William J, Taylor, Jack A, Teixeira, Manuel R, Terry, Mary Beth, Teulé, Alex, Thomassen, Mads, Thöne, Kathrin, Thull, Darcy L, Tischkowitz, Marc, Toland, Amanda E, Tollenaar, Rob AEM, Torres, Diana, Truong, Thérèse, Tung, Nadine, Vachon, Celine M, Van Asperen, Christi J, Van Den Ouweland, Ans MW, Van Rensburg, Elizabeth J, Vega, Ana, Viel, Alessandra, Vieiro-Balo, Paula, Wang, Qin, Wappenschmidt, Barbara, Weinberg, Clarice R, Weitzel, Jeffrey N, Wendt, Camilla, Winqvist, Robert, Yang, Xiaohong R, Yannoukakos, Drakoulis, Ziogas, Argyrios, Milne, Roger L, Easton, Douglas F, Chenevix-Trench, Georgia, Zheng, Wei, Kraft, Peter, and Jiang, Xia

Subjects
causal gene, TWAS, Vesicular Transport Proteins, Breast Neoplasms, Estrogens, Genomics, Risk Assessment, 3. Good health, Receptors, Estrogen, breast cancer subtype, GWAS, Humans, Female, Genetic Predisposition to Disease, Transcriptome, Genome-Wide Association Study
Abstract

Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.

32. A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer

Author

Wu, Lang, Shi, Wei, Long, Jirong, Guo, Xingyi, Michailidou, Kyriaki, Beesley, Jonathan, Bolla, Manjeet K, Shu, Xiao-Ou, Lu, Yingchang, Cai, Qiuyin, Al-Ejeh, Fares, Rozali, Esdy, Wang, Qin, Dennis, Joe, Li, Bingshan, Zeng, Chenjie, Feng, Helian, Gusev, Alexander, Barfield, Richard T, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J, Auer, Paul L, Barrdahl, Myrto, Baynes, Caroline, Beckmann, Matthias W, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Stig E, Brauch, Hiltrud, Brenner, Hermann, Brinton, Louise, Broberg, Per, Brucker, Sara Y, Burwinkel, Barbara, Caldés, Trinidad, Canzian, Federico, Carter, Brian D, Castelao, J Esteban, Chang-Claude, Jenny, Chen, Xiaoqing, Cheng, Ting-Yuan David, Christiansen, Hans, Clarke, Christine L, NBCS Collaborators, Collée, Margriet, Cornelissen, Sten, Couch, Fergus J, Cox, David, Cox, Angela, Cross, Simon S, Cunningham, Julie M, Czene, Kamila, Daly, Mary B, Devilee, Peter, Doheny, Kimberly F, Dörk, Thilo, Dos-Santos-Silva, Isabel, Dumont, Martine, Dwek, Miriam, Eccles, Diana M, Eilber, Ursula, Eliassen, A Heather, Engel, Christoph, Eriksson, Mikael, Fachal, Laura, Fasching, Peter A, Figueroa, Jonine, Flesch-Janys, Dieter, Fletcher, Olivia, Flyger, Henrik, Fritschi, Lin, Gabrielson, Marike, Gago-Dominguez, Manuela, Gapstur, Susan M, García-Closas, Montserrat, Gaudet, Mia M, Ghoussaini, Maya, Giles, Graham G, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Guénel, Pascal, Hahnen, Eric, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hallberg, Emily, Hamann, Ute, Harrington, Patricia, Hein, Alexander, Hicks, Belynda, Hillemanns, Peter, Hollestelle, Antoinette, Hoover, Robert N, Hopper, John L, Huang, Guanmengqian, Humphreys, Keith, Hunter, David J, Jakubowska, Anna, Janni, Wolfgang, John, Esther M, Johnson, Nichola, Jones, Kristine, Jones, Michael E, Jung, Audrey, Kaaks, Rudolf, Kerin, Michael J, Khusnutdinova, Elza, Kosma, Veli-Matti, Kristensen, Vessela N, Lambrechts, Diether, Le Marchand, Loic, Li, Jingmei, Lindström, Sara, Lissowska, Jolanta, Lo, Wing-Yee, Loibl, Sibylle, Lubinski, Jan, Luccarini, Craig, Lux, Michael P, MacInnis, Robert J, Maishman, Tom, Kostovska, Ivana Maleva, Mannermaa, Arto, Manson, JoAnn E, Margolin, Sara, Mavroudis, Dimitrios, Meijers-Heijboer, Hanne, Meindl, Alfons, Menon, Usha, Meyer, Jeffery, Mulligan, Anna Marie, Neuhausen, Susan L, Nevanlinna, Heli, Neven, Patrick, Nielsen, Sune F, Nordestgaard, Børge G, Olopade, Olufunmilayo I, Olson, Janet E, Olsson, Håkan, Peterlongo, Paolo, Peto, Julian, Plaseska-Karanfilska, Dijana, Prentice, Ross, Presneau, Nadege, Pylkäs, Katri, Rack, Brigitte, Radice, Paolo, Rahman, Nazneen, Rennert, Gad, Rennert, Hedy S, Rhenius, Valerie, Romero, Atocha, Romm, Jane, Rudolph, Anja, Saloustros, Emmanouil, Sandler, Dale P, Sawyer, Elinor J, Schmidt, Marjanka K, Schmutzler, Rita K, Schneeweiss, Andreas, Scott, Rodney J, Scott, Christopher G, Seal, Sheila, Shah, Mitul, Shrubsole, Martha J, Smeets, Ann, Southey, Melissa C, Spinelli, John J, Stone, Jennifer, Surowy, Harald, Swerdlow, Anthony J, Tamimi, Rulla M, Tapper, William, Taylor, Jack A, Terry, Mary Beth, Tessier, Daniel C, Thomas, Abigail, Thöne, Kathrin, Tollenaar, Rob AEM, Torres, Diana, Truong, Thérèse, Untch, Michael, Vachon, Celine, Van Den Berg, David, Vincent, Daniel, Waisfisz, Quinten, Weinberg, Clarice R, Wendt, Camilla, Whittemore, Alice S, Wildiers, Hans, Willett, Walter C, Winqvist, Robert, Wolk, Alicja, Xia, Lucy, Yang, Xiaohong R, Ziogas, Argyrios, Ziv, Elad, KConFab/AOCS Investigators, Dunning, Alison M, Pharoah, Paul DP, Simard, Jacques, Milne, Roger L, Edwards, Stacey L, Kraft, Peter, Easton, Douglas F, Chenevix-Trench, Georgia, and Zheng, Wei

Subjects
Risk, Case-Control Studies, Gene Expression, Humans, Breast Neoplasms, Female, Genetic Predisposition to Disease, Transcriptome, Polymorphism, Single Nucleotide, 3. Good health, Genome-Wide Association Study
Abstract

The breast cancer risk variants identified in genome-wide association studies explain only a small fraction of the familial relative risk, and the genes responsible for these associations remain largely unknown. To identify novel risk loci and likely causal genes, we performed a transcriptome-wide association study evaluating associations of genetically predicted gene expression with breast cancer risk in 122,977 cases and 105,974 controls of European ancestry. We used data from the Genotype-Tissue Expression Project to establish genetic models to predict gene expression in breast tissue and evaluated model performance using data from The Cancer Genome Atlas. Of the 8,597 genes evaluated, significant associations were identified for 48 at a Bonferroni-corrected threshold of P < 5.82 × 10-6, including 14 genes at loci not yet reported for breast cancer. We silenced 13 genes and showed an effect for 11 on cell proliferation and/or colony-forming efficiency. Our study provides new insights into breast cancer genetics and biology.

33. Combined Associations of a Polygenic Risk Score and Classical Risk Factors With Breast Cancer Risk

Author

Kapoor, Pooja Middha, Mavaddat, Nasim, Choudhury, Parichoy Pal, Wilcox, Amber N, Lindström, Sara, Behrens, Sabine, Michailidou, Kyriaki, Dennis, Joe, Bolla, Manjeet K, Wang, Qin, Jung, Audrey, Abu-Ful, Zomoroda, Ahearn, Thomas, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J, Auer, Paul L, Freeman, Laura E Beane, Becher, Heiko, Beckmann, Matthias W, Beeghly-Fadiel, Alicia, Benitez, Javier, Bernstein, Leslie, Bojesen, Stig E, Brauch, Hiltrud, Brenner, Hermann, Brüning, Thomas, Cai, Qiuyin, Campa, Daniele, Canzian, Federico, Carracedo, Angel, Carter, Brian D, Castelao, Jose E, Chanock, Stephen J, Chatterjee, Nilanjan, Chenevix-Trench, Georgia, Clarke, Christine L, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Dai, James Y, Earp, H Shelton, Ekici, Arif B, Eliassen, A Heather, Eriksson, Mikael, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine, Fritschi, Lin, Gabrielson, Marike, Gago-Dominguez, Manuela, Gao, Chi, Gapstur, Susan M, Gaudet, Mia M, Giles, Graham G, González-Neira, Anna, Guénel, Pascal, Haeberle, Lothar, Haiman, Christopher A, Håkansson, Niclas, Hall, Per, Hamann, Ute, Hatse, Sigrid, Heyworth, Jane, Holleczek, Bernd, Hoover, Robert N, Hopper, John L, Howell, Anthony, Hunter, David J, ABCTB Investigators, KConFab/AOCS Investigators, John, Esther M, Jones, Michael E, Kaaks, Rudolf, Keeman, Renske, Kitahara, Cari M, Ko, Yon-Dschun, Koutros, Stella, Kurian, Allison W, Lambrechts, Diether, Le Marchand, Loic, Lee, Eunjung, Lejbkowicz, Flavio, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, MacInnis, Robert J, Martinez, Maria Elena, Maurer, Tabea, McLean, Catriona, Neuhausen, Susan L, Newman, William G, Norman, Aaron, O'Brien, Katie M, Olshan, Andrew F, Olson, Janet E, Olsson, Håkan, Orr, Nick, Perou, Charles M, Pita, Guillermo, Polley, Eric C, Prentice, Ross L, Rennert, Gad, Rennert, Hedy S, Ruddy, Kathryn J, Sandler, Dale P, Saunders, Christobel, Schoemaker, Minouk J, Schöttker, Ben, Schumacher, Fredrick, Scott, Christopher, Scott, Rodney J, Shu, Xiao-Ou, Smeets, Ann, Southey, Melissa C, Spinelli, John J, Stone, Jennifer, Swerdlow, Anthony J, Tamimi, Rulla M, Taylor, Jack A, Troester, Melissa A, Vachon, Celine M, Van Veen, Elke M, Wang, Xiaoliang, Weinberg, Clarice R, Weltens, Caroline, Willett, Walter, Winham, Stacey J, Wolk, Alicja, Yang, Xiaohong R, Zheng, Wei, Ziogas, Argyrios, Dunning, Alison M, Pharoah, Paul DP, Schmidt, Marjanka K, Kraft, Peter, Easton, Douglas F, Milne, Roger L, García-Closas, Montserrat, and Chang-Claude, Jenny

Subjects
Aged, 80 and over, Breast Neoplasms, Middle Aged, Polymorphism, Single Nucleotide, White People, 3. Good health, Body Mass Index, Logistic Models, Receptors, Estrogen, Risk Factors, Case-Control Studies, Humans, Female, Genetic Predisposition to Disease, 10. No inequality, Medical History Taking, Aged
Abstract

We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.

34. Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types

Author

Kar, Siddhartha P, Beesley, Jonathan, Amin Al Olama, Ali, Michailidou, Kyriaki, Tyrer, Jonathan, Kote-Jarai, ZSofia, Lawrenson, Kate, Lindstrom, Sara, Ramus, Susan J, Thompson, Deborah J, ABCTB Investigators, Kibel, Adam S, Dansonka-Mieszkowska, Agnieszka, Michael, Agnieszka, Dieffenbach, Aida K, Gentry-Maharaj, Aleksandra, Whittemore, Alice S, Wolk, Alicja, Monteiro, Alvaro, Peixoto, Ana, Kierzek, Andrzej, Cox, Angela, Rudolph, Anja, Gonzalez-Neira, Anna, Wu, Anna H, Lindblom, Annika, Swerdlow, Anthony, AOCS Study Group & Australian Cancer Study (Ovarian Cancer), APCB BioResource, Ziogas, Argyrios, Ekici, Arif B, Burwinkel, Barbara, Karlan, Beth Y, Nordestgaard, Børge G, Blomqvist, Carl, Phelan, Catherine, McLean, Catriona, Pearce, Celeste Leigh, Vachon, Celine, Cybulski, Cezary, Slavov, Chavdar, Stegmaier, Christa, Maier, Christiane, Ambrosone, Christine B, Høgdall, Claus K, Teerlink, Craig C, Kang, Daehee, Tessier, Daniel C, Schaid, Daniel J, Stram, Daniel O, Cramer, Daniel W, Neal, David E, Eccles, Diana, Flesch-Janys, Dieter, Edwards, Digna R Velez, Wokozorczyk, Dominika, Levine, Douglas A, Yannoukakos, Drakoulis, Sawyer, Elinor J, Bandera, Elisa V, Poole, Elizabeth M, Goode, Ellen L, Khusnutdinova, Elza, Høgdall, Estrid, Song, Fengju, Bruinsma, Fiona, Heitz, Florian, Modugno, Francesmary, Hamdy, Freddie C, Wiklund, Fredrik, Giles, Graham G, Olsson, Håkan, Wildiers, Hans, Ulmer, Hans-Ulrich, Pandha, Hardev, Risch, Harvey A, Darabi, Hatef, Salvesen, Helga B, Nevanlinna, Heli, Gronberg, Henrik, Brenner, Hermann, Brauch, Hiltrud, Anton-Culver, Hoda, Song, Honglin, Lim, Hui-Yi, McNeish, Iain, Campbell, Ian, Vergote, Ignace, Gronwald, Jacek, Lubiński, Jan, Stanford, Janet L, Benítez, Javier, Doherty, Jennifer A, Permuth, Jennifer B, Chang-Claude, Jenny, Donovan, Jenny L, Dennis, Joe, Schildkraut, Joellen M, Schleutker, Johanna, Hopper, John L, Kupryjanczyk, Jolanta, Park, Jong Y, Figueroa, Jonine, Clements, Judith A, Knight, Julia A, Peto, Julian, Cunningham, Julie M, Pow-Sang, Julio, Batra, Jyotsna, Czene, Kamila, Lu, Karen H, Herkommer, Kathleen, Khaw, Kay-Tee, KConFab Investigators, Matsuo, Keitaro, Muir, Kenneth, Offitt, Kenneth, Chen, Kexin, Moysich, Kirsten B, Aittomäki, Kristiina, Odunsi, Kunle, Kiemeney, Lambertus A, Massuger, Leon FAG, Fitzgerald, Liesel M, Cook, Linda S, Cannon-Albright, Lisa, Hooning, Maartje J, Pike, Malcolm C, Bolla, Manjeet K, Luedeke, Manuel, Teixeira, Manuel R, Goodman, Marc T, Schmidt, Marjanka K, Riggan, Marjorie, Aly, Markus, Rossing, Mary Anne, Beckmann, Matthias W, Moisse, Matthieu, Sanderson, Maureen, Southey, Melissa C, Jones, Michael, Lush, Michael, Hildebrandt, Michelle AT, Hou, Ming-Feng, Schoemaker, Minouk J, Garcia-Closas, Montserrat, Bogdanova, Natalia, Rahman, Nazneen, NBCS Investigators, Le, Nhu D, Orr, Nick, Wentzensen, Nicolas, Pashayan, Nora, Peterlongo, Paolo, Guénel, Pascal, Brennan, Paul, Paulo, Paula, Webb, Penelope M, Broberg, Per, Fasching, Peter A, Devilee, Peter, Wang, Qin, Cai, Qiuyin, Li, Qiyuan, Kaneva, Radka, Butzow, Ralf, Kopperud, Reidun Kristin, Schmutzler, Rita K, Stephenson, Robert A, MacInnis, Robert J, Hoover, Robert N, Winqvist, Robert, Ness, Roberta, Milne, Roger L, Travis, Ruth C, Benlloch, Sara, Olson, Sara H, McDonnell, Shannon K, Tworoger, Shelley S, Maia, Sofia, Berndt, Sonja, Lee, Soo Chin, Teo, Soo-Hwang, Thibodeau, Stephen N, Bojesen, Stig E, Gapstur, Susan M, Kjær, Susanne Krüger, Pejovic, Tanja, Tammela, Teuvo LJ, GENICA Network, PRACTICAL Consortium, Dörk, Thilo, Brüning, Thomas, Wahlfors, Tiina, Key, Tim J, Edwards, Todd L, Menon, Usha, Hamann, Ute, Mitev, Vanio, Kosma, Veli-Matti, Setiawan, Veronica Wendy, Kristensen, Vessela, Arndt, Volker, Vogel, Walther, Zheng, Wei, Sieh, Weiva, Blot, William J, Kluzniak, Wojciech, Shu, Xiao-Ou, Gao, Yu-Tang, Schumacher, Fredrick, Freedman, Matthew L, Berchuck, Andrew, Dunning, Alison M, Simard, Jacques, Haiman, Christopher A, Spurdle, Amanda, Sellers, Thomas A, Hunter, David J, Henderson, Brian E, Kraft, Peter, Chanock, Stephen J, Couch, Fergus J, Hall, Per, Gayther, Simon A, Easton, Douglas F, Chenevix-Trench, Georgia, Eeles, Rosalind, Pharoah, Paul DP, and Lambrechts, Diether

Subjects
Male, Ovarian Neoplasms, Quantitative Trait Loci, Chromosome Mapping, Datasets as Topic, Prostatic Neoplasms, Breast Neoplasms, Polymorphism, Single Nucleotide, 3. Good health, Enhancer Elements, Genetic, Meta-Analysis as Topic, Genetic Loci, Organ Specificity, Case-Control Studies, Humans, Female, Gene Regulatory Networks, Genetic Predisposition to Disease, Genome-Wide Association Study, Signal Transduction
Abstract

UNLABELLED: Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis. SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.

35. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Author

Ahearn, Thomas U, Zhang, Haoyu, Michailidou, Kyriaki, Milne, Roger L, Bolla, Manjeet K, Dennis, Joe, Dunning, Alison M, Lush, Michael, Wang, Qin, Andrulis, Irene L, Anton-Culver, Hoda, Arndt, Volker, Aronson, Kristan J, Auer, Paul L, Augustinsson, Annelie, Baten, Adinda, Becher, Heiko, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Blomqvist, Carl, Bojesen, Stig E, Bonanni, Bernardo, Børresen-Dale, Anne-Lise, Brauch, Hiltrud, Brenner, Hermann, Brooks-Wilson, Angela, Brüning, Thomas, Burwinkel, Barbara, Buys, Saundra S, Canzian, Federico, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Chenevix-Trench, Georgia, Clarke, Christine L, NBCS Collaborators, Collée, J Margriet, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, Devilee, Peter, Dörk, Thilo, Dwek, Miriam, Eccles, Diana M, Evans, D Gareth, Fasching, Peter A, Figueroa, Jonine, Floris, Giuseppe, Gago-Dominguez, Manuela, Gapstur, Susan M, García-Sáenz, José A, Gaudet, Mia M, Giles, Graham G, Goldberg, Mark S, González-Neira, Anna, Alnæs, Grethe I Grenaker, Grip, Mervi, Guénel, Pascal, Haiman, Christopher A, Hall, Per, Hamann, Ute, Harkness, Elaine F, Heemskerk-Gerritsen, Bernadette AM, Holleczek, Bernd, Hollestelle, Antoinette, Hooning, Maartje J, Hoover, Robert N, Hopper, John L, Howell, Anthony, ABCTB Investigators, KConFab/AOCS Investigators, Jakimovska, Milena, Jakubowska, Anna, John, Esther M, Jones, Michael E, Jung, Audrey, Kaaks, Rudolf, Kauppila, Saila, Keeman, Renske, Khusnutdinova, Elza, Kitahara, Cari M, Ko, Yon-Dschun, Koutros, Stella, Kristensen, Vessela N, Krüger, Ute, Kubelka-Sabit, Katerina, Kurian, Allison W, Kyriacou, Kyriacos, Lambrechts, Diether, Lee, Derrick G, Lindblom, Annika, Linet, Martha, Lissowska, Jolanta, Llaneza, Ana, Lo, Wing-Yee, MacInnis, Robert J, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Martinez, Maria Elena, McLean, Catriona, Meindl, Alfons, Menon, Usha, Nevanlinna, Heli, Newman, William G, Nodora, Jesse, Offit, Kenneth, Olsson, Håkan, Orr, Nick, Park-Simon, Tjoung-Won, Patel, Alpa V, Peto, Julian, Pita, Guillermo, Plaseska-Karanfilska, Dijana, Prentice, Ross, Punie, Kevin, Pylkäs, Katri, Radice, Paolo, Rennert, Gad, Romero, Atocha, Rüdiger, Thomas, Saloustros, Emmanouil, Sampson, Sarah, Sandler, Dale P, Sawyer, Elinor J, Schmutzler, Rita K, Schoemaker, Minouk J, Schöttker, Ben, Sherman, Mark E, Shu, Xiao-Ou, Smichkoska, Snezhana, Southey, Melissa C, Spinelli, John J, Swerdlow, Anthony J, Tamimi, Rulla M, Tapper, William J, Taylor, Jack A, Teras, Lauren R, Terry, Mary Beth, Torres, Diana, Troester, Melissa A, Vachon, Celine M, Van Deurzen, Carolien HM, Van Veen, Elke M, Wagner, Philippe, Weinberg, Clarice R, Wendt, Camilla, Wesseling, Jelle, Winqvist, Robert, Wolk, Alicja, Yang, Xiaohong R, Zheng, Wei, Couch, Fergus J, Simard, Jacques, Kraft, Peter, Easton, Douglas F, Pharoah, Paul DP, Schmidt, Marjanka K, García-Closas, Montserrat, and Chatterjee, Nilanjan

Subjects
Common breast cancer susceptibility variants, Risk, Receptor, ErbB-2, Genetic predisposition, Etiologic heterogeneity, Breast Neoplasms, 3. Good health, Breast cancer, Receptors, Estrogen, Biomarkers, Tumor, Humans, Female, Receptors, Progesterone, Genome-Wide Association Study
Abstract

BACKGROUND: Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. METHODS: Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. RESULTS: Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. CONCLUSION: This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.

36. Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

Author

Ferreira, Manuel A, Gamazon, Eric R, Al-Ejeh, Fares, Aittomäki, Kristiina, Andrulis, Irene L, Anton-Culver, Hoda, Arason, Adalgeir, Arndt, Volker, Aronson, Kristan J, Arun, Banu K, Asseryanis, Ella, Azzollini, Jacopo, Balmaña, Judith, Barnes, Daniel R, Barrowdale, Daniel, Beckmann, Matthias W, Behrens, Sabine, Benitez, Javier, Bermisheva, Marina, Białkowska, Katarzyna, Blomqvist, Carl, Bogdanova, Natalia V, Bojesen, Stig E, Bolla, Manjeet K, Borg, Ake, Brauch, Hiltrud, Brenner, Hermann, Broeks, Annegien, Burwinkel, Barbara, Caldés, Trinidad, Caligo, Maria A, Campa, Daniele, Campbell, Ian, Canzian, Federico, Carter, Jonathan, Carter, Brian D, Castelao, Jose E, Chang-Claude, Jenny, Chanock, Stephen J, Christiansen, Hans, Chung, Wendy K, Claes, Kathleen BM, Clarke, Christine L, EMBRACE Collaborators, GC-HBOC Study Collaborators, GEMO Study Collaborators, Couch, Fergus J, Cox, Angela, Cross, Simon S, Czene, Kamila, Daly, Mary B, De La Hoya, Miguel, Dennis, Joe, Devilee, Peter, Diez, Orland, Dörk, Thilo, Dunning, Alison M, Dwek, Miriam, Eccles, Diana M, Ejlertsen, Bent, Ellberg, Carolina, Engel, Christoph, Eriksson, Mikael, Fasching, Peter A, Fletcher, Olivia, Flyger, Henrik, Friedman, Eitan, Frost, Debra, Gabrielson, Marike, Gago-Dominguez, Manuela, Ganz, Patricia A, Gapstur, Susan M, Garber, Judy, García-Closas, Montserrat, García-Sáenz, José A, Gaudet, Mia M, Giles, Graham G, Glendon, Gord, Godwin, Andrew K, Goldberg, Mark S, Goldgar, David E, González-Neira, Anna, Greene, Mark H, Gronwald, Jacek, Guénel, Pascal, Haiman, Christopher A, Hall, Per, Hamann, Ute, He, Wei, Heyworth, Jane, Hogervorst, Frans BL, Hollestelle, Antoinette, Hoover, Robert N, Hopper, John L, Hulick, Peter J, Humphreys, Keith, Imyanitov, Evgeny N, ABCTB Investigators, HEBON Investigators, BCFR Investigators, Isaacs, Claudine, Jakimovska, Milena, Jakubowska, Anna, James, Paul A, Janavicius, Ramunas, Jankowitz, Rachel C, John, Esther M, Johnson, Nichola, Joseph, Vijai, Karlan, Beth Y, Khusnutdinova, Elza, Kiiski, Johanna I, Ko, Yon-Dschun, Jones, Michael E, Konstantopoulou, Irene, Kristensen, Vessela N, Laitman, Yael, Lambrechts, Diether, Lazaro, Conxi, Leslie, Goska, Lester, Jenny, Lesueur, Fabienne, Lindström, Sara, Long, Jirong, Loud, Jennifer T, Lubiński, Jan, Makalic, Enes, Mannermaa, Arto, Manoochehri, Mehdi, Margolin, Sara, Maurer, Tabea, Mavroudis, Dimitrios, McGuffog, Lesley, Meindl, Alfons, Menon, Usha, Michailidou, Kyriaki, Miller, Austin, Montagna, Marco, Moreno, Fernando, Moserle, Lidia, Mulligan, Anna Marie, Nathanson, Katherine L, Neuhausen, Susan L, Nevanlinna, Heli, Nevelsteen, Ines, Nielsen, Finn C, Nikitina-Zake, Liene, Nussbaum, Robert L, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I, Olsson, Håkan, Osorio, Ana, Papp, Janos, Park-Simon, Tjoung-Won, Parsons, Michael T, Pedersen, Inge Sokilde, Peixoto, Ana, Peterlongo, Paolo, Pharoah, Paul DP, Plaseska-Karanfilska, Dijana, Poppe, Bruce, Presneau, Nadege, Radice, Paolo, Rantala, Johanna, Rennert, Gad, Risch, Harvey A, Saloustros, Emmanouil, Sanden, Kristin, Sawyer, Elinor J, Schmidt, Marjanka K, Schmutzler, Rita K, Sharma, Priyanka, Shu, Xiao-Ou, Simard, Jacques, Singer, Christian F, Soucy, Penny, Southey, Melissa C, Spinelli, John J, Spurdle, Amanda B, Stone, Jennifer, Swerdlow, Anthony J, Tapper, William J, Taylor, Jack A, Teixeira, Manuel R, Terry, Mary Beth, Teulé, Alex, Thomassen, Mads, Thöne, Kathrin, Thull, Darcy L, Tischkowitz, Marc, Toland, Amanda E, Torres, Diana, Truong, Thérèse, Tung, Nadine, Vachon, Celine M, Van Asperen, Christi J, Van Den Ouweland, Ans MW, Van Rensburg, Elizabeth J, Vega, Ana, Viel, Alessandra, Wang, Qin, Wappenschmidt, Barbara, Weitzel, Jeffrey N, Wendt, Camilla, Winqvist, Robert, Yang, Xiaohong R, Yannoukakos, Drakoulis, Ziogas, Argyrios, Kraft, Peter, Antoniou, Antonis C, Zheng, Wei, Easton, Douglas F, Milne, Roger L, Beesley, Jonathan, and Chenevix-Trench, Georgia

Subjects
Gene Expression Profiling, Quantitative Trait Loci, Humans, Breast Neoplasms, Female, Genetic Predisposition to Disease, skin and connective tissue diseases, 3. Good health, Genome-Wide Association Study
Abstract

Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer.

37. Genetic risk variants associated with in situ breast cancer

Author

Ruth C. Travis, Sara Lindström, Christopher A. Haiman, Peter Kraft, Loic Le Marchand, Rudolf Kaaks, Federico Canzian, Petra H.M. Peeters, Stephen J. Chanock, Elisabete Weiderpass, Aditi Hazra, Dimitrios Trichopoulos, Mia M. Gaudet, Walter C. Willett, Salvatore Panico, Robert N. Hoover, Afshan Siddiq, Susan M. Gapstur, Brian E. Henderson, Amit Joshi, Susan E. Hankinson, Malin Sund, David J. Hunter, Myrto Barrdahl, Amanda Black, W. Ryan Diver, Pilar Amiano, Anne Tjønneland, Laure Dossus, Daniele Campa, Regina G. Ziegler, Campa, Daniele, Barrdahl, Myrto, Gaudet, Mia M, Black, Amanda, Chanock, Stephen J, Diver, W. Ryan, Gapstur, Susan M, Haiman, Christopher, Hankinson, Susan, Hazra, Aditi, Henderson, Brian, Hoover, Robert N, Hunter, David J, Joshi, Amit D, Kraft, Peter, Le Marchand, Loic, Lindström, Sara, Willett, Walter, Travis, Ruth C, Amiano, Pilar, Siddiq, Afshan, Trichopoulos, Dimitrio, Sund, Malin, Tjønneland, Anne, Weiderpass, Elisabete, Peeters, Petra H, Panico, Salvatore, Dossus, Laure, Ziegler, Regina G, Canzian, Federico, and Kaaks, Rudolf

Subjects
Oncology, Cancer Research, IDENTIFIES 2, Genome-wide association study, Bioinformatics, GENOME-WIDE ASSOCIATION, SUSCEPTIBILITY LOCI, PROSTATE-CANCER, COMMON VARIANTS, CONFER SUSCEPTIBILITY, CLINICAL-SIGNIFICANCE, COHORT CONSORTIUM, CARCINOMA, WOMEN, Prostate cancer, Non-U.S. Gov't, Medicine(all), VDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801, Research Support, Non-U.S. Gov't, Population Surveillance, Female, Case-Control Studie, Medical Genetics, Breast Neoplasm, Carcinoma in Situ, Research Article, Human, Risk, medicine.medical_specialty, Breast Neoplasms, Single-nucleotide polymorphism, Research Support, Polymorphism, Single Nucleotide, Breast cancer, Internal medicine, medicine, Journal Article, Humans, Genetic Predisposition to Disease, Medicinsk genetik, Cancer och onkologi, business.industry, Carcinoma in situ, CDKN2BAS, Case-control study, Cancer, Genetic Variation, medicine.disease, Case-Control Studies, Cancer and Oncology, VDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801, business
Abstract

Introduction Breast cancer in situ (BCIS) diagnoses, a precursor lesion for invasive breast cancer, comprise about 20 % of all breast cancers (BC) in countries with screening programs. Family history of BC is considered one of the strongest risk factors for BCIS. Methods To evaluate the association of BC susceptibility loci with BCIS risk, we genotyped 39 single nucleotide polymorphisms (SNPs), associated with risk of invasive BC, in 1317 BCIS cases, 10,645 invasive BC cases, and 14,006 healthy controls in the National Cancer Institute’s Breast and Prostate Cancer Cohort Consortium (BPC3). Using unconditional logistic regression models adjusted for age and study, we estimated the association of SNPs with BCIS using two different comparison groups: healthy controls and invasive BC subjects to investigate whether BCIS and BC share a common genetic profile. Results We found that five SNPs (CDKN2BAS-rs1011970, FGFR2-rs3750817, FGFR2-rs2981582, TNRC9-rs3803662, 5p12-rs10941679) were significantly associated with BCIS risk (P value adjusted for multiple comparisons

Published
2015

Catalog

Books, media, physical & digital resources
See catalog results