96 results on '"Severi, Gianluca"'
Search Results
2. Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study
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Haycock, Philip C, Burgess, Stephen, Nounu, Aayah, Zheng, Jie, Okoli, George N, Bowden, Jack, Wade, Kaitlin Hazel, Timpson, Nicholas J, Evans, David M, Willeit, Peter, Aviv, Abraham, Gaunt, Tom R, Hemani, Gibran, Mangino, Massimo, Ellis, Hayley Patricia, Kurian, Kathreena M, Pooley, Karen A, Eeles, Rosalind A, Lee, Jeffrey E, Fang, Shenying, Chen, Wei V, Law, Matthew H, Bowdler, Lisa M, Iles, Mark M, Yang, Qiong, Worrall, Bradford B, Markus, Hugh Stephen, Hung, Rayjean J, Amos, Chris I, Spurdle, Amanda B, Thompson, Deborah J, O’Mara, Tracy A, Wolpin, Brian, Amundadottir, Laufey, Stolzenberg-Solomon, Rachael, Trichopoulou, Antonia, Onland-Moret, N Charlotte, Lund, Eiliv, Duell, Eric J, Canzian, Federico, Severi, Gianluca, Overvad, Kim, Gunter, Marc J, Tumino, Rosario, Svenson, Ulrika, van Rij, Andre, Baas, Annette F, Bown, Matthew J, Samani, Nilesh J, van t’Hof, Femke NG, Tromp, Gerard, Jones, Gregory T, Kuivaniemi, Helena, Elmore, James R, Johansson, Mattias, Mckay, James, Scelo, Ghislaine, Carreras-Torres, Robert, Gaborieau, Valerie, Brennan, Paul, Bracci, Paige M, Neale, Rachel E, Olson, Sara H, Gallinger, Steven, Li, Donghui, Petersen, Gloria M, Risch, Harvey A, Klein, Alison P, Han, Jiali, Abnet, Christian C, Freedman, Neal D, Taylor, Philip R, Maris, John M, Aben, Katja K, Kiemeney, Lambertus A, Vermeulen, Sita H, Wiencke, John K, Walsh, Kyle M, Wrensch, Margaret, Rice, Terri, Turnbull, Clare, Litchfield, Kevin, Paternoster, Lavinia, Standl, Marie, Abecasis, Gonçalo R, SanGiovanni, John Paul, Li, Yong, Mijatovic, Vladan, Sapkota, Yadav, Low, Siew-Kee, Zondervan, Krina T, Montgomery, Grant W, Nyholt, Dale R, van Heel, David A, Hunt, Karen, Arking, Dan E, Ashar, Foram N, Sotoodehnia, Nona, Woo, Daniel, and Rosand, Jonathan
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Rare Diseases ,Clinical Research ,Cancer ,Prevention ,Genetics ,Aetiology ,2.1 Biological and endogenous factors ,Adult ,Aged ,Aged ,80 and over ,Cardiovascular Diseases ,Female ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Germ-Line Mutation ,Humans ,Male ,Mendelian Randomization Analysis ,Middle Aged ,Neoplasms ,Polymorphism ,Single Nucleotide ,Risk Assessment ,Telomere ,Telomere Homeostasis ,Telomeres Mendelian Randomization Collaboration ,Public Health and Health Services ,Oncology and carcinogenesis - Abstract
ImportanceThe causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation.ObjectiveTo conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases.Data sourcesGenomewide association studies (GWAS) published up to January 15, 2015.Study selectionGWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available.Data extraction and synthesisSummary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population.Main outcomes and measuresOdds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation.ResultsSummary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]).Conclusions and relevanceIt is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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- 2017
3. Association Between Telomere Length and Risk of Cancer and Non-Neoplastic Diseases: A Mendelian Randomization Study.
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Telomeres Mendelian Randomization Collaboration, Haycock, Philip C, Burgess, Stephen, Nounu, Aayah, Zheng, Jie, Okoli, George N, Bowden, Jack, Wade, Kaitlin Hazel, Timpson, Nicholas J, Evans, David M, Willeit, Peter, Aviv, Abraham, Gaunt, Tom R, Hemani, Gibran, Mangino, Massimo, Ellis, Hayley Patricia, Kurian, Kathreena M, Pooley, Karen A, Eeles, Rosalind A, Lee, Jeffrey E, Fang, Shenying, Chen, Wei V, Law, Matthew H, Bowdler, Lisa M, Iles, Mark M, Yang, Qiong, Worrall, Bradford B, Markus, Hugh Stephen, Hung, Rayjean J, Amos, Chris I, Spurdle, Amanda B, Thompson, Deborah J, O'Mara, Tracy A, Wolpin, Brian, Amundadottir, Laufey, Stolzenberg-Solomon, Rachael, Trichopoulou, Antonia, Onland-Moret, N Charlotte, Lund, Eiliv, Duell, Eric J, Canzian, Federico, Severi, Gianluca, Overvad, Kim, Gunter, Marc J, Tumino, Rosario, Svenson, Ulrika, van Rij, Andre, Baas, Annette F, Bown, Matthew J, Samani, Nilesh J, van t'Hof, Femke NG, Tromp, Gerard, Jones, Gregory T, Kuivaniemi, Helena, Elmore, James R, Johansson, Mattias, Mckay, James, Scelo, Ghislaine, Carreras-Torres, Robert, Gaborieau, Valerie, Brennan, Paul, Bracci, Paige M, Neale, Rachel E, Olson, Sara H, Gallinger, Steven, Li, Donghui, Petersen, Gloria M, Risch, Harvey A, Klein, Alison P, Han, Jiali, Abnet, Christian C, Freedman, Neal D, Taylor, Philip R, Maris, John M, Aben, Katja K, Kiemeney, Lambertus A, Vermeulen, Sita H, Wiencke, John K, Walsh, Kyle M, Wrensch, Margaret, Rice, Terri, Turnbull, Clare, Litchfield, Kevin, Paternoster, Lavinia, Standl, Marie, Abecasis, Gonçalo R, SanGiovanni, John Paul, Li, Yong, Mijatovic, Vladan, Sapkota, Yadav, Low, Siew-Kee, Zondervan, Krina T, Montgomery, Grant W, Nyholt, Dale R, van Heel, David A, Hunt, Karen, Arking, Dan E, Ashar, Foram N, Sotoodehnia, Nona, and Woo, Daniel
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Telomeres Mendelian Randomization Collaboration ,Telomere ,Humans ,Neoplasms ,Cardiovascular Diseases ,Genetic Predisposition to Disease ,Risk Assessment ,Germ-Line Mutation ,Polymorphism ,Single Nucleotide ,Adult ,Aged ,Aged ,80 and over ,Middle Aged ,Female ,Male ,Genome-Wide Association Study ,Mendelian Randomization Analysis ,Telomere Homeostasis ,Polymorphism ,Single Nucleotide ,and over ,Prevention ,Clinical Research ,Cancer ,Genetics ,Rare Diseases ,2.1 Biological and endogenous factors ,Oncology and Carcinogenesis ,Public Health and Health Services - Abstract
ImportanceThe causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation.ObjectiveTo conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases.Data sourcesGenomewide association studies (GWAS) published up to January 15, 2015.Study selectionGWAS of noncommunicable diseases that assayed germline genetic variation and did not select cohort or control participants on the basis of preexisting diseases. Of 163 GWAS of noncommunicable diseases identified, summary data from 103 were available.Data extraction and synthesisSummary association statistics for single nucleotide polymorphisms (SNPs) that are strongly associated with telomere length in the general population.Main outcomes and measuresOdds ratios (ORs) and 95% confidence intervals (CIs) for disease per standard deviation (SD) higher telomere length due to germline genetic variation.ResultsSummary data were available for 35 cancers and 48 non-neoplastic diseases, corresponding to 420 081 cases (median cases, 2526 per disease) and 1 093 105 controls (median, 6789 per disease). Increased telomere length due to germline genetic variation was generally associated with increased risk for site-specific cancers. The strongest associations (ORs [95% CIs] per 1-SD change in genetically increased telomere length) were observed for glioma, 5.27 (3.15-8.81); serous low-malignant-potential ovarian cancer, 4.35 (2.39-7.94); lung adenocarcinoma, 3.19 (2.40-4.22); neuroblastoma, 2.98 (1.92-4.62); bladder cancer, 2.19 (1.32-3.66); melanoma, 1.87 (1.55-2.26); testicular cancer, 1.76 (1.02-3.04); kidney cancer, 1.55 (1.08-2.23); and endometrial cancer, 1.31 (1.07-1.61). Associations were stronger for rarer cancers and at tissue sites with lower rates of stem cell division. There was generally little evidence of association between genetically increased telomere length and risk of psychiatric, autoimmune, inflammatory, diabetic, and other non-neoplastic diseases, except for coronary heart disease (OR, 0.78 [95% CI, 0.67-0.90]), abdominal aortic aneurysm (OR, 0.63 [95% CI, 0.49-0.81]), celiac disease (OR, 0.42 [95% CI, 0.28-0.61]) and interstitial lung disease (OR, 0.09 [95% CI, 0.05-0.15]).Conclusions and relevanceIt is likely that longer telomeres increase risk for several cancers but reduce risk for some non-neoplastic diseases, including cardiovascular diseases.
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- 2017
4. The causal relevance of body mass index in different histological types of lung cancer: A Mendelian randomization study
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Carreras-Torres, Robert, Haycock, Philip C, Relton, Caroline L, Martin, Richard M, Smith, George Davey, Kraft, Peter, Gao, Chi, Tworoger, Shelley, Le Marchand, Loïc, Wilkens, Lynne R, Park, Sungshim L, Haiman, Christopher, Field, John K, Davies, Michael, Marcus, Michael, Liu, Geoffrey, Caporaso, Neil E, Christiani, David C, Wei, Yongyue, Chen, Chu, Doherty, Jennifer A, Severi, Gianluca, Goodman, Gary E, Hung, Rayjean J, Amos, Christopher I, McKay, James, Johansson, Mattias, and Brennan, Paul
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Epidemiology ,Biomedical and Clinical Sciences ,Health Sciences ,Oncology and Carcinogenesis ,Genetics ,Tobacco ,Lung ,Tobacco Smoke and Health ,Prevention ,Lung Cancer ,Cancer ,Respiratory ,Good Health and Well Being ,Body Mass Index ,Case-Control Studies ,Female ,Humans ,Lung Neoplasms ,Male ,Mendelian Randomization Analysis ,Risk Factors ,Smoking - Abstract
Body mass index (BMI) is inversely associated with lung cancer risk in observational studies, even though it increases the risk of several other cancers, which could indicate confounding by tobacco smoking or reverse causality. We used the two-sample Mendelian randomization (MR) approach to circumvent these limitations of observational epidemiology by constructing a genetic instrument for BMI, based on results from the GIANT consortium, which was evaluated in relation to lung cancer risk using GWAS results on 16,572 lung cancer cases and 21,480 controls. Results were stratified by histological subtype, smoking status and sex. An increase of one standard deviation (SD) in BMI (4.65 Kg/m(2)) raised the risk for lung cancer overall (OR = 1.13; P = 0.10). This was driven by associations with squamous cell (SQ) carcinoma (OR = 1.45; P = 1.2 × 10(-3)) and small cell (SC) carcinoma (OR = 1.81; P = 0.01). An inverse trend was seen for adenocarcinoma (AD) (OR = 0.82; P = 0.06). In stratified analyses, a 1 SD increase in BMI was inversely associated with overall lung cancer in never smokers (OR = 0.50; P = 0.02). These results indicate that higher BMI may increase the risk of certain types of lung cancer, in particular SQ and SC carcinoma.
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- 2016
5. A Meta-analysis of Individual Participant Data Reveals an Association between Circulating Levels of IGF-I and Prostate Cancer Risk
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Travis, Ruth C, Appleby, Paul N, Martin, Richard M, Holly, Jeff MP, Albanes, Demetrius, Black, Amanda, Bueno-de-Mesquita, HB As, Chan, June M, Chen, Chu, Chirlaque, Maria-Dolores, Cook, Michael B, Deschasaux, Mélanie, Donovan, Jenny L, Ferrucci, Luigi, Galan, Pilar, Giles, Graham G, Giovannucci, Edward L, Gunter, Marc J, Habel, Laurel A, Hamdy, Freddie C, Helzlsouer, Kathy J, Hercberg, Serge, Hoover, Robert N, Janssen, Joseph AMJL, Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loic, Metter, E Jeffrey, Mikami, Kazuya, Morris, Joan K, Neal, David E, Neuhouser, Marian L, Ozasa, Kotaro, Palli, Domenico, Platz, Elizabeth A, Pollak, Michael, Price, Alison J, Roobol, Monique J, Schaefer, Catherine, Schenk, Jeannette M, Severi, Gianluca, Stampfer, Meir J, Stattin, Pär, Tamakoshi, Akiko, Tangen, Catherine M, Touvier, Mathilde, Wald, Nicholas J, Weiss, Noel S, Ziegler, Regina G, Key, Timothy J, and Allen, Naomi E
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Biomedical and Clinical Sciences ,Clinical Sciences ,Oncology and Carcinogenesis ,Aging ,Prostate Cancer ,Cancer ,Urologic Diseases ,Aged ,Humans ,Insulin-Like Growth Factor I ,Male ,Middle Aged ,Prostatic Neoplasms ,Risk Factors ,Oncology & Carcinogenesis ,Biochemistry and cell biology ,Oncology and carcinogenesis - Abstract
The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. After mutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development. Cancer Res; 76(8); 2288-300. ©2016 AACR.
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- 2016
6. Fine mapping of chromosome 5p15.33 based on a targeted deep sequencing and high density genotyping identifies novel lung cancer susceptibility loci
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Kachuri, Linda, Amos, Christopher I, McKay, James D, Johansson, Mattias, Vineis, Paolo, Bueno-de-Mesquita, H Bas, Boutron-Ruault, Marie-Christine, Johansson, Mikael, Quirós, J Ramón, Sieri, Sabina, Travis, Ruth C, Weiderpass, Elisabete, Le Marchand, Loic, Henderson, Brian E, Wilkens, Lynne, Goodman, Gary E, Chen, Chu, Doherty, Jennifer A, Christiani, David C, Wei, Yongyue, Su, Li, Tworoger, Shelley, Zhang, Xuehong, Kraft, Peter, Zaridze, David, Field, John K, Marcus, Michael W, Davies, Michael PA, Hyde, Russell, Caporaso, Neil E, Landi, Maria Teresa, Severi, Gianluca, Giles, Graham G, Liu, Geoffrey, McLaughlin, John R, Li, Yafang, Xiao, Xiangjun, Fehringer, Gord, Zong, Xuchen, Denroche, Robert E, Zuzarte, Philip C, McPherson, John D, Brennan, Paul, and Hung, Rayjean J
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Lung ,Human Genome ,Genetics ,Cancer ,Prevention ,Lung Cancer ,2.1 Biological and endogenous factors ,Aetiology ,Case-Control Studies ,Chromosome Mapping ,Chromosomes ,Human ,Pair 5 ,Female ,Genetic Loci ,Genetic Predisposition to Disease ,Genotyping Techniques ,Humans ,Lung Neoplasms ,Male ,Middle Aged ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
Chromosome 5p15.33 has been identified as a lung cancer susceptibility locus, however the underlying causal mechanisms were not fully elucidated. Previous fine-mapping studies of this locus have relied on imputation or investigated a small number of known, common variants. This study represents a significant advance over previous research by investigating a large number of novel, rare variants, as well as their underlying mechanisms through telomere length. Variants for this fine-mapping study were identified through a targeted deep sequencing (average depth of coverage greater than 4000×) of 576 individuals. Subsequently, 4652 SNPs, including 1108 novel SNPs, were genotyped in 5164 cases and 5716 controls of European ancestry. After adjusting for known risk loci, rs2736100 and rs401681, we identified a new, independent lung cancer susceptibility variant in LPCAT1: rs139852726 (OR = 0.46, P = 4.73×10(-9)), and three new adenocarcinoma risk variants in TERT: rs61748181 (OR = 0.53, P = 2.64×10(-6)), rs112290073 (OR = 1.85, P = 1.27×10(-5)), rs138895564 (OR = 2.16, P = 2.06×10(-5); among young cases, OR = 3.77, P = 8.41×10(-4)). In addition, we found that rs139852726 (P = 1.44×10(-3)) was associated with telomere length in a sample of 922 healthy individuals. The gene-based SKAT-O analysis implicated TERT as the most relevant gene in the 5p15.33 region for adenocarcinoma (P = 7.84×10(-7)) and lung cancer (P = 2.37×10(-5)) risk. In this largest fine-mapping study to investigate a large number of rare and novel variants within 5p15.33, we identified novel lung and adenocarcinoma susceptibility loci with large effects and provided support for the role of telomere length as the potential underlying mechanism.
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- 2016
7. Carotenoids, retinol, tocopherols, and prostate cancer risk: pooled analysis of 15 studies 1–3
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Key, Timothy J, Appleby, Paul N, Travis, Ruth C, Albanes, Demetrius, Alberg, Anthony J, Barricarte, Aurelio, Black, Amanda, Boeing, Heiner, Bueno-de-Mesquita, H Bas, Chan, June M, Chen, Chu, Cook, Michael B, Donovan, Jenny L, Galan, Pilar, Gilbert, Rebecca, Giles, Graham G, Giovannucci, Edward, Goodman, Gary E, Goodman, Phyllis J, Gunter, Marc J, Hamdy, Freddie C, Heliövaara, Markku, Helzlsouer, Kathy J, Henderson, Brian E, Hercberg, Serge, Hoffman-Bolton, Judy, Hoover, Robert N, Johansson, Mattias, Khaw, Kay-Tee, King, Irena B, Knekt, Paul, Kolonel, Laurence N, Le Marchand, Loic, Männistö, Satu, Martin, Richard M, Meyer, Haakon E, Mondul, Alison M, Moy, Kristin A, Neal, David E, Neuhouser, Marian L, Palli, Domenico, Platz, Elizabeth A, Pouchieu, Camille, Rissanen, Harri, Schenk, Jeannette M, Severi, Gianluca, Stampfer, Meir J, Tjønneland, Anne, Touvier, Mathilde, Trichopoulou, Antonia, Weinstein, Stephanie J, Ziegler, Regina G, Zhou, Cindy Ke, Allen, Naomi E, Biomarkers, Endogenous Hormones Nutritional, and Group, Prostate Cancer Collaborative
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Prevention ,Urologic Diseases ,Nutrition ,Prostate Cancer ,Cancer ,Aging ,Clinical Research ,Adult ,Biomarkers ,Carotenoids ,Case-Control Studies ,Cohort Studies ,Cross-Sectional Studies ,Humans ,Lycopene ,Male ,Meta-Analysis as Topic ,Middle Aged ,Neoplasm Grading ,Neoplasm Staging ,Observational Studies as Topic ,Prospective Studies ,Prostate ,Prostatic Neoplasms ,Risk Factors ,Vitamin A ,alpha-Tocopherol ,prostate cancer ,carotenoids ,retinol ,tocopherols ,vitamin E ,vitamin A ,pooled analysis ,nested case-control study ,biomarkers ,Endogenous Hormones Nutritional Biomarkers Prostate Cancer Collaborative Group ,Engineering ,Medical and Health Sciences ,Nutrition & Dietetics ,Clinical sciences ,Nutrition and dietetics - Abstract
BackgroundIndividual studies have suggested that circulating carotenoids, retinol, or tocopherols may be associated with prostate cancer risk, but the studies have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease.ObjectiveThe objective of this study was to conduct a pooled analysis of the associations of the concentrations of 7 carotenoids, retinol, α-tocopherol, and γ-tocopherol with risk of prostate cancer and to describe whether any associations differ by stage or grade of the disease or other factors.DesignPrincipal investigators of prospective studies provided individual participant data for prostate cancer cases and controls. Risk by study-specific fifths of each biomarker was estimated by using multivariable-adjusted conditional logistic regression in matched case-control sets.ResultsData were available for up to 11,239 cases (including 1654 advanced stage and 1741 aggressive) and 18,541 controls from 15 studies. Lycopene was not associated with overall risk of prostate cancer, but there was statistically significant heterogeneity by stage of disease, and the OR for aggressive disease for the highest compared with the lowest fifth of lycopene was 0.65 (95% CI: 0.46, 0.91; P-trend = 0.032). No other carotenoid was significantly associated with overall risk of prostate cancer or with risk of advanced-stage or aggressive disease. For retinol, the OR for the highest compared with the lowest fifth was 1.13 (95% CI: 1.04, 1.22; P-trend = 0.015). For α-tocopherol, the OR for the highest compared with the lowest fifth was 0.86 (95% CI: 0.78, 0.94; P-trend < 0.001), with significant heterogeneity by stage of disease; the OR for aggressive prostate cancer was 0.74 (95% CI: 0.59, 0.92; P-trend = 0.001). γ-Tocopherol was not associated with risk.ConclusionsOverall prostate cancer risk was positively associated with retinol and inversely associated with α-tocopherol, and risk of aggressive prostate cancer was inversely associated with lycopene and α-tocopherol. Whether these associations reflect causal relations is unclear.
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- 2015
8. Erratum: Corrigendum: Genome-wide association study of colorectal cancer identifies six new susceptibility loci
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Schumacher, Fredrick R, Schmit, Stephanie L, Jiao, Shuo, Edlund, Christopher K, Wang, Hansong, Zhang, Ben, Hsu, Li, Huang, Shu-Chen, Fischer, Christopher P, Harju, John F, Idos, Gregory E, Lejbkowicz, Flavio, Manion, Frank J, McDonnell, Kevin, McNeil, Caroline E, Melas, Marilena, Rennert, Hedy S, Shi, Wei, Thomas, Duncan C, Van Den Berg, David J, Hutter, Carolyn M, Aragaki, Aaron K, Butterbach, Katja, Caan, Bette J, Carlson, Christopher S, Chanock, Stephen J, Curtis, Keith R, Fuchs, Charles S, Gala, Manish, Giovannucci, Edward L, Gogarten, Stephanie M, Hayes, Richard B, Henderson, Brian, Hunter, David J, Jackson, Rebecca D, Kolonel, Laurence N, Kooperberg, Charles, Küry, Sébastien, LaCroix, Andrea, Laurie, Cathy C, Laurie, Cecelia A, Lemire, Mathieu, Levine, David, Ma, Jing, Makar, Karen W, Qu, Conghui, Taverna, Darin, Ulrich, Cornelia M, Wu, Kana, Kono, Suminori, West, Dee W, Berndt, Sonja I, Bezieau, Stephane, Brenner, Hermann, Campbell, Peter T, Chan, Andrew T, Chang-Claude, Jenny, Coetzee, Gerhard A, Conti, David V, Duggan, David, Figueiredo, Jane C, Fortini, Barbara K, Gallinger, Steven J, Gauderman, W James, Giles, Graham, Green, Roger, Haile, Robert, Harrison, Tabitha A, Hoffmeister, Michael, Hopper, John L, Hudson, Thomas J, Jacobs, Eric, Iwasaki, Motoki, Jee, Sun Ha, Jenkins, Mark, Jia, Wei-Hua, Joshi, Amit, Li, Li, Lindor, Noralene M, Matsuo, Keitaro, Moreno, Victor, Mukherjee, Bhramar, Newcomb, Polly A, Potter, John D, Raskin, Leon, Rennert, Gad, Rosse, Stephanie, Severi, Gianluca, Schoen, Robert E, Seminara, Daniela, Shu, Xiao-Ou, Slattery, Martha L, Tsugane, Shoichiro, White, Emily, Xiang, Yong-Bing, Zanke, Brent W, Zheng, Wei, Le Marchand, Loic, Casey, Graham, and Gruber, Stephen B
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Biological Sciences ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Digestive Diseases ,Cancer ,Colo-Rectal Cancer - Published
- 2015
9. Genome-wide association study of colorectal cancer identifies six new susceptibility loci.
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Schumacher, Fredrick R, Schmit, Stephanie L, Jiao, Shuo, Edlund, Christopher K, Wang, Hansong, Zhang, Ben, Hsu, Li, Huang, Shu-Chen, Fischer, Christopher P, Harju, John F, Idos, Gregory E, Lejbkowicz, Flavio, Manion, Frank J, McDonnell, Kevin, McNeil, Caroline E, Melas, Marilena, Rennert, Hedy S, Shi, Wei, Thomas, Duncan C, Van Den Berg, David J, Hutter, Carolyn M, Aragaki, Aaron K, Butterbach, Katja, Caan, Bette J, Carlson, Christopher S, Chanock, Stephen J, Curtis, Keith R, Fuchs, Charles S, Gala, Manish, Giovannucci, Edward L, Gogarten, Stephanie M, Hayes, Richard B, Henderson, Brian, Hunter, David J, Jackson, Rebecca D, Kolonel, Laurence N, Kooperberg, Charles, Küry, Sébastien, LaCroix, Andrea, Laurie, Cathy C, Laurie, Cecelia A, Lemire, Mathieu, Levine, David, Ma, Jing, Makar, Karen W, Qu, Conghui, Taverna, Darin, Ulrich, Cornelia M, Wu, Kana, Kono, Suminori, West, Dee W, Berndt, Sonja I, Bezieau, Stéphane, Brenner, Hermann, Campbell, Peter T, Chan, Andrew T, Chang-Claude, Jenny, Coetzee, Gerhard A, Conti, David V, Duggan, David, Figueiredo, Jane C, Fortini, Barbara K, Gallinger, Steven J, Gauderman, W James, Giles, Graham, Green, Roger, Haile, Robert, Harrison, Tabitha A, Hoffmeister, Michael, Hopper, John L, Hudson, Thomas J, Jacobs, Eric, Iwasaki, Motoki, Jee, Sun Ha, Jenkins, Mark, Jia, Wei-Hua, Joshi, Amit, Li, Li, Lindor, Noralene M, Matsuo, Keitaro, Moreno, Victor, Mukherjee, Bhramar, Newcomb, Polly A, Potter, John D, Raskin, Leon, Rennert, Gad, Rosse, Stephanie, Severi, Gianluca, Schoen, Robert E, Seminara, Daniela, Shu, Xiao-Ou, Slattery, Martha L, Tsugane, Shoichiro, White, Emily, Xiang, Yong-Bing, Zanke, Brent W, and Zheng, Wei
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Humans ,Colorectal Neoplasms ,Genetic Predisposition to Disease ,Odds Ratio ,Case-Control Studies ,Polymorphism ,Single Nucleotide ,Genome-Wide Association Study ,Genetics ,Digestive Diseases ,Prevention ,Cancer ,Human Genome ,Colo-Rectal Cancer ,2.1 Biological and endogenous factors ,MD Multidisciplinary - Abstract
Genetic susceptibility to colorectal cancer is caused by rare pathogenic mutations and common genetic variants that contribute to familial risk. Here we report the results of a two-stage association study with 18,299 cases of colorectal cancer and 19,656 controls, with follow-up of the most statistically significant genetic loci in 4,725 cases and 9,969 controls from two Asian consortia. We describe six new susceptibility loci reaching a genome-wide threshold of P
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- 2015
10. A Prospective Study of the Immune System Activation Biomarker Neopterin and Colorectal Cancer Risk
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Aleksandrova, Krasimira, Chuang, Shu-Chun, Boeing, Heiner, Zuo, Hui, Tell, Grethe S, Pischon, Tobias, Jenab, Mazda, Bueno-de-Mesquita, Bas, Vollset, Stein Emil, Midttun, Øivind, Ueland, Per Magne, Fedirko, Veronika, Johansson, Mattias, Weiderpass, Elisabete, Severi, Gianluca, Racine, Antoine, Boutron-Ruault, Marie-Christine, Kaaks, Rudolf, Kühn, Tilman, Tjønneland, Anne, Overvad, Kim, Quirós, J Ramón, Jakszyn, Paula, Sánchez, María-José, Dorronsoro, Miren, Chirlaque, Maria-Dolores, Ardanaz, Eva, Khaw, Kay-Tee, Wareham, Nicholas J, Travis, Ruth C, Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrios, Palli, Domenico, Sieri, Sabina, Tumino, Rosario, Panico, Salvatore, May, Anne M, Palmqvist, Richard, Ljuslinder, Ingrid, Kong, So Yeon J, Freisling, Heinz, Gunter, Marc J, Lu, Yunxia, Cross, Amanda J, Riboli, Elio, and Vineis, Paolo
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Colo-Rectal Cancer ,Cancer ,Clinical Research ,Digestive Diseases ,Adult ,Aged ,Biomarkers ,Tumor ,Case-Control Studies ,Chromatography ,Liquid ,Colonic Neoplasms ,Colorectal Neoplasms ,Europe ,Female ,Humans ,Immunity ,Cellular ,Male ,Middle Aged ,Neopterin ,Odds Ratio ,Prospective Studies ,Rectal Neoplasms ,Sensitivity and Specificity ,T-Lymphocytes ,Helper-Inducer ,Tandem Mass Spectrometry ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
Neopterin may be relevant for colorectal cancer (CRC) development, as a biomarker of cellular immune activity exerting pleiotropic effects on cellular ageing, oxidative stress, and inflammation. So far, the association between prediagnostic neopterin and colon and rectal cancer risk has not been evaluated in human populations. A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort using data on plasma concentrations of total neopterin (T-N, sum of neopterin and 7,8-dihydroneopterin) in 830 incident CRC case patients (561 colon and 269 rectal) matched within risk sets to 830 control participants. A subsequent replication study used data from the Hordaland Health Study, where 173 CRC case patients have been diagnosed among 6594 healthy participants over 12 years of follow-up. After multivariable adjustment for a priori chosen CRC risk factors, a "U-shaped" association of T-N with CRC was revealed. Compared with the second quintile of the T-N distribution, the relative risks for the first, third, fourth, and fifth quintiles were 2.37 (95% CI = 1.66 to 3.39), 1.24 (95% CI = 0.87 to 1.77), 1.55 (95% CI = 1.08 to 2.22), and 2.31 (95% CI = 1.63 to 3.27), respectively. Replication of these associations within the Hordaland Health Study yielded similar results. No differences have been observed when the associations were explored by colon and rectal cancer site (two-sided P difference = .87) and after excluding case patients diagnosed within the first four follow-up years. These novel findings provide evidence of the role of both suppressed and activated cell-mediated immunity as reflected by prediagnostic T-N concentrations in the development of CRC.
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- 2015
11. A genome-wide association study of marginal zone lymphoma shows association to the HLA region
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Vijai, Joseph, Wang, Zhaoming, Berndt, Sonja I, Skibola, Christine F, Slager, Susan L, de Sanjose, Silvia, Melbye, Mads, Glimelius, Bengt, Bracci, Paige M, Conde, Lucia, Birmann, Brenda M, Wang, Sophia S, Brooks-Wilson, Angela R, Lan, Qing, de Bakker, Paul IW, Vermeulen, Roel CH, Portlock, Carol, Ansell, Stephen M, Link, Brian K, Riby, Jacques, North, Kari E, Gu, Jian, Hjalgrim, Henrik, Cozen, Wendy, Becker, Nikolaus, Teras, Lauren R, Spinelli, John J, Turner, Jenny, Zhang, Yawei, Purdue, Mark P, Giles, Graham G, Kelly, Rachel S, Zeleniuch-Jacquotte, Anne, Ennas, Maria Grazia, Monnereau, Alain, Bertrand, Kimberly A, Albanes, Demetrius, Lightfoot, Tracy, Yeager, Meredith, Chung, Charles C, Burdett, Laurie, Hutchinson, Amy, Lawrence, Charles, Montalvan, Rebecca, Liang, Liming, Huang, Jinyan, Ma, Baoshan, Villano, Danylo J, Maria, Ann, Corines, Marina, Thomas, Tinu, Novak, Anne J, Dogan, Ahmet, Liebow, Mark, Thompson, Carrie A, Witzig, Thomas E, Habermann, Thomas M, Weiner, George J, Smith, Martyn T, Holly, Elizabeth A, Jackson, Rebecca D, Tinker, Lesley F, Ye, Yuanqing, Adami, Hans-Olov, Smedby, Karin E, De Roos, Anneclaire J, Hartge, Patricia, Morton, Lindsay M, Severson, Richard K, Benavente, Yolanda, Boffetta, Paolo, Brennan, Paul, Foretova, Lenka, Maynadie, Marc, McKay, James, Staines, Anthony, Diver, W Ryan, Vajdic, Claire M, Armstrong, Bruce K, Kricker, Anne, Zheng, Tongzhang, Holford, Theodore R, Severi, Gianluca, Vineis, Paolo, Ferri, Giovanni M, Ricco, Rosalia, Miligi, Lucia, Clavel, Jacqueline, Giovannucci, Edward, Kraft, Peter, Virtamo, Jarmo, Smith, Alex, Kane, Eleanor, Roman, Eve, Chiu, Brian CH, Fraumeni, Joseph F, Wu, Xifeng, Cerhan, James R, Offit, Kenneth, and Chanock, Stephen J
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Lymphoma ,Cancer ,Genetics ,Hematology ,Rare Diseases ,Human Genome ,Aetiology ,2.1 Biological and endogenous factors ,Butyrophilins ,Computational Biology ,Genome-Wide Association Study ,Genotype ,Humans ,Lymphoma ,B-Cell ,Marginal Zone ,Major Histocompatibility Complex ,Membrane Glycoproteins ,Polymorphism ,Single Nucleotide ,White People - Abstract
Marginal zone lymphoma (MZL) is the third most common subtype of B-cell non-Hodgkin lymphoma. Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127 controls of European ancestry and identify two independent loci near BTNL2 (rs9461741, P=3.95 × 10(-15)) and HLA-B (rs2922994, P=2.43 × 10(-9)) in the HLA region significantly associated with MZL risk. This is the first evidence that genetic variation in the major histocompatibility complex influences MZL susceptibility.
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- 2015
12. Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma
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Cerhan, James R, Berndt, Sonja I, Vijai, Joseph, Ghesquières, Hervé, McKay, James, Wang, Sophia S, Wang, Zhaoming, Yeager, Meredith, Conde, Lucia, de Bakker, Paul IW, Nieters, Alexandra, Cox, David, Burdett, Laurie, Monnereau, Alain, Flowers, Christopher R, De Roos, Anneclaire J, Brooks-Wilson, Angela R, Lan, Qing, Severi, Gianluca, Melbye, Mads, Gu, Jian, Jackson, Rebecca D, Kane, Eleanor, Teras, Lauren R, Purdue, Mark P, Vajdic, Claire M, Spinelli, John J, Giles, Graham G, Albanes, Demetrius, Kelly, Rachel S, Zucca, Mariagrazia, Bertrand, Kimberly A, Zeleniuch-Jacquotte, Anne, Lawrence, Charles, Hutchinson, Amy, Zhi, Degui, Habermann, Thomas M, Link, Brian K, Novak, Anne J, Dogan, Ahmet, Asmann, Yan W, Liebow, Mark, Thompson, Carrie A, Ansell, Stephen M, Witzig, Thomas E, Weiner, George J, Veron, Amelie S, Zelenika, Diana, Tilly, Hervé, Haioun, Corinne, Molina, Thierry Jo, Hjalgrim, Henrik, Glimelius, Bengt, Adami, Hans-Olov, Bracci, Paige M, Riby, Jacques, Smith, Martyn T, Holly, Elizabeth A, Cozen, Wendy, Hartge, Patricia, Morton, Lindsay M, Severson, Richard K, Tinker, Lesley F, North, Kari E, Becker, Nikolaus, Benavente, Yolanda, Boffetta, Paolo, Brennan, Paul, Foretova, Lenka, Maynadie, Marc, Staines, Anthony, Lightfoot, Tracy, Crouch, Simon, Smith, Alex, Roman, Eve, Diver, W Ryan, Offit, Kenneth, Zelenetz, Andrew, Klein, Robert J, Villano, Danylo J, Zheng, Tongzhang, Zhang, Yawei, Holford, Theodore R, Kricker, Anne, Turner, Jenny, Southey, Melissa C, Clavel, Jacqueline, Virtamo, Jarmo, Weinstein, Stephanie, Riboli, Elio, Vineis, Paolo, Kaaks, Rudolph, Trichopoulos, Dimitrios, Vermeulen, Roel CH, Boeing, Heiner, Tjonneland, Anne, Angelucci, Emanuele, Di Lollo, Simonetta, Rais, Marco, and Birmann, Brenda M
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Human Genome ,Rare Diseases ,Genetics ,Cancer ,Hematology ,Lymphoma ,Aetiology ,2.1 Biological and endogenous factors ,Chromosome Mapping ,Computational Biology ,Genetic Loci ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Genotype ,Humans ,Likelihood Functions ,Lymphoma ,Large B-Cell ,Diffuse ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,White People ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - Abstract
Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 × 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 × 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 × 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 × 10(-13) and 3.63 × 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.
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- 2014
13. Genome-wide Association Study Identifies Five Susceptibility Loci for Follicular Lymphoma outside the HLA Region
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Skibola, Christine F, Berndt, Sonja I, Vijai, Joseph, Conde, Lucia, Wang, Zhaoming, Yeager, Meredith, de Bakker, Paul IW, Birmann, Brenda M, Vajdic, Claire M, Foo, Jia-Nee, Bracci, Paige M, Vermeulen, Roel CH, Slager, Susan L, de Sanjose, Silvia, Wang, Sophia S, Linet, Martha S, Salles, Gilles, Lan, Qing, Severi, Gianluca, Hjalgrim, Henrik, Lightfoot, Tracy, Melbye, Mads, Gu, Jian, Ghesquières, Hervé, Link, Brian K, Morton, Lindsay M, Holly, Elizabeth A, Smith, Alex, Tinker, Lesley F, Teras, Lauren R, Kricker, Anne, Becker, Nikolaus, Purdue, Mark P, Spinelli, John J, Zhang, Yawei, Giles, Graham G, Vineis, Paolo, Monnereau, Alain, Bertrand, Kimberly A, Albanes, Demetrius, Zeleniuch-Jacquotte, Anne, Gabbas, Attilio, Chung, Charles C, Burdett, Laurie, Hutchinson, Amy, Lawrence, Charles, Montalvan, Rebecca, Liang, Liming, Huang, Jinyan, Ma, Baoshan, Liu, Jianjun, Adami, Hans-Olov, Glimelius, Bengt, Ye, Yuanqing, Nowakowski, Grzegorz S, Dogan, Ahmet, Thompson, Carrie A, Habermann, Thomas M, Novak, Anne J, Liebow, Mark, Witzig, Thomas E, Weiner, George J, Schenk, Maryjean, Hartge, Patricia, De Roos, Anneclaire J, Cozen, Wendy, Zhi, Degui, Akers, Nicholas K, Riby, Jacques, Smith, Martyn T, Lacher, Mortimer, Villano, Danylo J, Maria, Ann, Roman, Eve, Kane, Eleanor, Jackson, Rebecca D, North, Kari E, Diver, W Ryan, Turner, Jenny, Armstrong, Bruce K, Benavente, Yolanda, Boffetta, Paolo, Brennan, Paul, Foretova, Lenka, Maynadie, Marc, Staines, Anthony, McKay, James, Brooks-Wilson, Angela R, Zheng, Tongzhang, Holford, Theodore R, Chamosa, Saioa, Kaaks, Rudolph, Kelly, Rachel S, Ohlsson, Bodil, Travis, Ruth C, Weiderpass, Elisabete, Clavel, Jacqueline, Giovannucci, Edward, Kraft, Peter, and Virtamo, Jarmo
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Hematology ,Cancer ,Clinical Research ,Human Genome ,Lymphoma ,Genetics ,Rare Diseases ,2.1 Biological and endogenous factors ,Aetiology ,Alleles ,Biomarkers ,Tumor ,Case-Control Studies ,Chromosomes ,Human ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,HLA Antigens ,Haplotypes ,Humans ,Lymphoma ,Follicular ,Polymorphism ,Single Nucleotide ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Genome-wide association studies (GWASs) of follicular lymphoma (FL) have previously identified human leukocyte antigen (HLA) gene variants. To identify additional FL susceptibility loci, we conducted a large-scale two-stage GWAS in 4,523 case subjects and 13,344 control subjects of European ancestry. Five non-HLA loci were associated with FL risk: 11q23.3 (rs4938573, p = 5.79 × 10(-20)) near CXCR5; 11q24.3 (rs4937362, p = 6.76 × 10(-11)) near ETS1; 3q28 (rs6444305, p = 1.10 × 10(-10)) in LPP; 18q21.33 (rs17749561, p = 8.28 × 10(-10)) near BCL2; and 8q24.21 (rs13254990, p = 1.06 × 10(-8)) near PVT1. In an analysis of the HLA region, we identified four linked HLA-DRβ1 multiallelic amino acids at positions 11, 13, 28, and 30 that were associated with FL risk (pomnibus = 4.20 × 10(-67) to 2.67 × 10(-70)). Additional independent signals included rs17203612 in HLA class II (odds ratio [OR(per-allele)] = 1.44; p = 4.59 × 10(-16)) and rs3130437 in HLA class I (OR(per-allele) = 1.23; p = 8.23 × 10(-9)). Our findings further expand the number of loci associated with FL and provide evidence that multiple common variants outside the HLA region make a significant contribution to FL risk.
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- 2014
14. Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study.
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Johnson, Nichola, Dudbridge, Frank, Orr, Nick, Gibson, Lorna, Jones, Michael E, Schoemaker, Minouk J, Folkerd, Elizabeth J, Haynes, Ben P, Hopper, John L, Southey, Melissa C, Dite, Gillian S, Apicella, Carmel, Schmidt, Marjanka K, Broeks, Annegien, Van't Veer, Laura J, Atsma, Femke, Muir, Kenneth, Lophatananon, Artitaya, Fasching, Peter A, Beckmann, Matthias W, Ekici, Arif B, Renner, Stefan P, Sawyer, Elinor, Tomlinson, Ian, Kerin, Michael, Miller, Nicola, Burwinkel, Barbara, Marme, Frederik, Schneeweiss, Andreas, Sohn, Christof, Guénel, Pascal, Truong, Therese, Cordina, Emilie, Menegaux, Florence, Bojesen, Stig E, Nordestgaard, Børge G, Flyger, Henrik, Milne, Roger, Zamora, M Pilar, Arias Perez, Jose Ignacio, Benitez, Javier, Bernstein, Leslie, Anton-Culver, Hoda, Ziogas, Argyrios, Clarke Dur, Christina, Brenner, Hermann, Müller, Heiko, Arndt, Volker, Dieffenbach, Aida Karina, Meindl, Alfons, Heil, Joerg, Bartram, Claus R, Schmutzler, Rita K, Brauch, Hiltrud, Justenhoven, Christina, Ko, Yon-Dschun, GENICA (Gene Environment Interaction and Breast Cancer in Germany) Network, Nevanlinna, Heli, Muranen, Taru A, Aittomäki, Kristiina, Blomqvist, Carl, Matsuo, Keitaro, Dörk, Thilo, Bogdanova, Natalia V, Antonenkova, Natalia N, Lindblom, Annika, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Hartikainen, Jaana M, Chenevix-Trench, Georgia, Beesley, Jonathan, kConFab Investigators, Australian Ovarian Cancer Study Group, Wu, Anna H, Van den Berg, David, Tseng, Chiu-Chen, Lambrechts, Diether, Smeets, Dominiek, Neven, Patrick, Wildiers, Hans, Chang-Claude, Jenny, Rudolph, Anja, Nickels, Stefan, Flesch-Janys, Dieter, Radice, Paolo, Peterlongo, Paolo, Bonanni, Bernardo, Pensotti, Valeria, Couch, Fergus J, Olson, Janet E, Wang, Xianshu, Fredericksen, Zachary, Pankratz, Vernon S, Giles, Graham G, Severi, Gianluca, Baglietto, Laura, Haiman, Chris, Simard, Jacques, and Goldberg, Mark S
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GENICA (Gene Environment Interaction and Breast Cancer in Germany) Network ,kConFab Investigators ,Australian Ovarian Cancer Study Group ,Humans ,Breast Neoplasms ,Genetic Predisposition to Disease ,Reproductive History ,Risk Factors ,Age Factors ,Age of Onset ,Premenopause ,Menarche ,Genotype ,Polymorphism ,Single Nucleotide ,Adult ,Aged ,Middle Aged ,European Continental Ancestry Group ,Female ,Cytochrome P-450 CYP3A ,Genetic Association Studies ,Human Genome ,Aging ,Clinical Research ,Cancer ,Genetics ,Breast Cancer ,Oncology & Carcinogenesis ,Oncology and Carcinogenesis - Abstract
IntroductionWe have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years.MethodsWe further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics.ResultsWe confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (P(trend) = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P(trend) = 0.005) but not cases (P(trend) = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P(het) = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (OR(het) = 0.84, 95% CI 0.75, 0.94; OR(hom) = 0.81, 95% CI 0.51, 1.30; P(trend) = 0.002) but not for those who had their menarche age ≤11 years (OR(het) = 1.06, 95% CI 0.95, 1.19, OR(hom) = 1.07, 95% CI 0.67, 1.72; P(trend) = 0.29).ConclusionsTo our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.
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- 2014
15. Genome-wide association study of subtype-specific epithelial ovarian cancer risk alleles using pooled DNA
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Earp, Madalene A, Kelemen, Linda E, Magliocco, Anthony M, Swenerton, Kenneth D, Chenevix-Trench, Georgia, Australian Cancer Study, Australian Ovarian Cancer Study Group, Lu, Yi, Hein, Alexander, Ekici, Arif B, Beckmann, Matthias W, Fasching, Peter A, Lambrechts, Diether, Despierre, Evelyn, Vergote, Ignace, Lambrechts, Sandrina, Doherty, Jennifer A, Rossing, Mary Anne, Chang-Claude, Jenny, Rudolph, Anja, Friel, Grace, Moysich, Kirsten B, Odunsi, Kunle, Sucheston-Campbell, Lara, Lurie, Galina, Goodman, Marc T, Carney, Michael E, Thompson, Pamela J, Runnebaum, Ingo B, Dürst, Matthias, Hillemanns, Peter, Dörk, Thilo, Antonenkova, Natalia, Bogdanova, Natalia, Leminen, Arto, Nevanlinna, Heli, Pelttari, Liisa M, Butzow, Ralf, Bunker, Clareann H, Modugno, Francesmary, Edwards, Robert P, Ness, Roberta B, du Bois, Andreas, Heitz, Florian, Schwaab, Ira, Harter, Philipp, Karlan, Beth Y, Walsh, Christine, Lester, Jenny, Jensen, Allan, Kjær, Susanne K, Høgdall, Claus K, Høgdall, Estrid, Lundvall, Lene, Sellers, Thomas A, Fridley, Brooke L, Goode, Ellen L, Cunningham, Julie M, Vierkant, Robert A, Giles, Graham G, Baglietto, Laura, Severi, Gianluca, Southey, Melissa C, Liang, Dong, Wu, Xifeng, Lu, Karen, Hildebrandt, Michelle AT, Levine, Douglas A, Bisogna, Maria, Schildkraut, Joellen M, Iversen, Edwin S, Weber, Rachel Palmieri, Berchuck, Andrew, Cramer, Daniel W, Terry, Kathryn L, Poole, Elizabeth M, Tworoger, Shelley S, Bandera, Elisa V, Chandran, Urmila, Orlow, Irene, Olson, Sara H, Wik, Elisabeth, Salvesen, Helga B, Bjorge, Line, Halle, Mari K, van Altena, Anne M, Aben, Katja KH, Kiemeney, Lambertus A, Massuger, Leon FAG, Pejovic, Tanja, Bean, Yukie T, Cybulski, Cezary, Gronwald, Jacek, Lubinski, Jan, Wentzensen, Nicolas, Brinton, Louise A, Lissowska, Jolanta, Garcia-Closas, Montserrat, Dicks, Ed, and Dennis, Joe
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Biological Sciences ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Genetics ,Rare Diseases ,Prevention ,Ovarian Cancer ,Human Genome ,Cancer ,2.1 Biological and endogenous factors ,Aetiology ,Alleles ,Carcinoma ,Ovarian Epithelial ,DNA ,Female ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Neoplasms ,Glandular and Epithelial ,Ovarian Neoplasms ,Polymorphism ,Single Nucleotide ,Quality Control ,Australian Cancer Study ,Australian Ovarian Cancer Study Group ,Ovarian Cancer Association Consortium ,Complementary and Alternative Medicine ,Paediatrics and Reproductive Medicine ,Genetics & Heredity ,Reproductive medicine - Abstract
Epithelial ovarian cancer (EOC) is a heterogeneous cancer with both genetic and environmental risk factors. Variants influencing the risk of developing the less-common EOC subtypes have not been fully investigated. We performed a genome-wide association study (GWAS) of EOC according to subtype by pooling genomic DNA from 545 cases and 398 controls of European descent, and testing for allelic associations. We evaluated for replication 188 variants from the GWAS [56 variants for mucinous, 55 for endometrioid and clear cell, 53 for low-malignant potential (LMP) serous, and 24 for invasive serous EOC], selected using pre-defined criteria. Genotypes from 13,188 cases and 23,164 controls of European descent were used to perform unconditional logistic regression under the log-additive genetic model; odds ratios (OR) and 95 % confidence intervals are reported. Nine variants tagging six loci were associated with subtype-specific EOC risk at P
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- 2014
16. Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer.
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Purrington, Kristen S, Slager, Susan, Eccles, Diana, Yannoukakos, Drakoulis, Fasching, Peter A, Miron, Penelope, Carpenter, Jane, Chang-Claude, Jenny, Martin, Nicholas G, Montgomery, Grant W, Kristensen, Vessela, Anton-Culver, Hoda, Goodfellow, Paul, Tapper, William J, Rafiq, Sajjad, Gerty, Susan M, Durcan, Lorraine, Konstantopoulou, Irene, Fostira, Florentia, Vratimos, Athanassios, Apostolou, Paraskevi, Konstanta, Irene, Kotoula, Vassiliki, Lakis, Sotiris, Dimopoulos, Meletios A, Skarlos, Dimosthenis, Pectasides, Dimitrios, Fountzilas, George, Beckmann, Matthias W, Hein, Alexander, Ruebner, Matthias, Ekici, Arif B, Hartmann, Arndt, Schulz-Wendtland, Ruediger, Renner, Stefan P, Janni, Wolfgang, Rack, Brigitte, Scholz, Christoph, Neugebauer, Julia, Andergassen, Ulrich, Lux, Michael P, Haeberle, Lothar, Clarke, Christine, Pathmanathan, Nirmala, Rudolph, Anja, Flesch-Janys, Dieter, Nickels, Stefan, Olson, Janet E, Ingle, James N, Olswold, Curtis, Slettedahl, Seth, Eckel-Passow, Jeanette E, Anderson, S Keith, Visscher, Daniel W, Cafourek, Victoria L, Sicotte, Hugues, Prodduturi, Naresh, Weiderpass, Elisabete, Bernstein, Leslie, Ziogas, Argyrios, Ivanovich, Jennifer, Giles, Graham G, Baglietto, Laura, Southey, Melissa, Kosma, Veli-Matti, Fischer, Hans-Peter, GENICA Network, Reed, Malcom WR, Cross, Simon S, Deming-Halverson, Sandra, Shrubsole, Martha, Cai, Qiuyin, Shu, Xiao-Ou, Daly, Mary, Weaver, Joellen, Ross, Eric, Klemp, Jennifer, Sharma, Priyanka, Torres, Diana, Rüdiger, Thomas, Wölfing, Heidrun, Ulmer, Hans-Ulrich, Försti, Asta, Khoury, Thaer, Kumar, Shicha, Pilarski, Robert, Shapiro, Charles L, Greco, Dario, Heikkilä, Päivi, Aittomäki, Kristiina, Blomqvist, Carl, Irwanto, Astrid, Liu, Jianjun, Pankratz, Vernon Shane, Wang, Xianshu, Severi, Gianluca, Mannermaa, Arto, Easton, Douglas, Hall, Per, and Brauch, Hiltrud
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GENICA Network ,Chromosomes ,Human ,Pair 19 ,Humans ,Genetic Predisposition to Disease ,Estrogen Receptor alpha ,Case-Control Studies ,Polymorphism ,Single Nucleotide ,Quantitative Trait Loci ,Adult ,Aged ,Aged ,80 and over ,Middle Aged ,Female ,Genome-Wide Association Study ,Young Adult ,Triple Negative Breast Neoplasms ,Prevention ,Genetics ,Cancer ,Breast Cancer ,Clinical Research ,Human Genome ,2.1 Biological and endogenous factors ,Chromosomes ,Human ,Pair 19 ,Polymorphism ,Single Nucleotide ,and over ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 × 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 × 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 × 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 × 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction.
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- 2014
17. Risk of ovarian cancer and the NF-κB pathway: genetic association with IL1A and TNFSF10.
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Charbonneau, Bridget, Block, Matthew S, Bamlet, William R, Vierkant, Robert A, Kalli, Kimberly R, Fogarty, Zachary, Rider, David N, Sellers, Thomas A, Tworoger, Shelley S, Poole, Elizabeth, Risch, Harvey A, Salvesen, Helga B, Kiemeney, Lambertus A, Baglietto, Laura, Giles, Graham G, Severi, Gianluca, Trabert, Britton, Wentzensen, Nicolas, Chenevix-Trench, Georgia, for AOCS/ACS group, Whittemore, Alice S, Sieh, Weiva, Chang-Claude, Jenny, Bandera, Elisa V, Orlow, Irene, Terry, Kathryn, Goodman, Marc T, Thompson, Pamela J, Cook, Linda S, Rossing, Mary Anne, Ness, Roberta B, Narod, Steven A, Kupryjanczyk, Jolanta, Lu, Karen, Butzow, Ralf, Dörk, Thilo, Pejovic, Tanja, Campbell, Ian, Le, Nhu D, Bunker, Clareann H, Bogdanova, Natalia, Runnebaum, Ingo B, Eccles, Diana, Paul, James, Wu, Anna H, Gayther, Simon A, Hogdall, Estrid, Heitz, Florian, Kaye, Stanley B, Karlan, Beth Y, Anton-Culver, Hoda, Gronwald, Jacek, Hogdall, Claus K, Lambrechts, Diether, Fasching, Peter A, Menon, Usha, Schildkraut, Joellen, Pearce, Celeste Leigh, Levine, Douglas A, Kjaer, Susanne Kruger, Cramer, Daniel, Flanagan, James M, Phelan, Catherine M, Brown, Robert, Massuger, Leon FAG, Song, Honglin, Doherty, Jennifer A, Krakstad, Camilla, Liang, Dong, Odunsi, Kunle, Berchuck, Andrew, Jensen, Allan, Lubinski, Jan, Nevanlinna, Heli, Bean, Yukie T, Lurie, Galina, Ziogas, Argyrios, Walsh, Christine, Despierre, Evelyn, Brinton, Louise, Hein, Alexander, Rudolph, Anja, Dansonka-Mieszkowska, Agnieszka, Olson, Sara H, Harter, Philipp, Tyrer, Jonathan, Vitonis, Allison F, Brooks-Wilson, Angela, Aben, Katja K, Pike, Malcolm C, Ramus, Susan J, Wik, Elisabeth, Cybulski, Cezary, Lin, Jie, Sucheston, Lara, Edwards, Robert, McGuire, Valerie, Lester, Jenny, du Bois, Andreas, and Lundvall, Lene
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for AOCS/ACS group ,Humans ,Ovarian Neoplasms ,NF-kappa B ,Risk ,Case-Control Studies ,Signal Transduction ,Polymorphism ,Single Nucleotide ,Female ,TNF-Related Apoptosis-Inducing Ligand ,Interleukin-1alpha ,Genetic Association Studies ,Polymorphism ,Single Nucleotide ,Prevention ,Ovarian Cancer ,Cancer ,Human Genome ,Rare Diseases ,Genetics ,Clinical Research ,2.1 Biological and endogenous factors ,Oncology & Carcinogenesis ,Oncology and Carcinogenesis - Abstract
A missense single-nucleotide polymorphism (SNP) in the immune modulatory gene IL1A has been associated with ovarian cancer risk (rs17561). Although the exact mechanism through which this SNP alters risk of ovarian cancer is not clearly understood, rs17561 has also been associated with risk of endometriosis, an epidemiologic risk factor for ovarian cancer. Interleukin-1α (IL1A) is both regulated by and able to activate NF-κB, a transcription factor family that induces transcription of many proinflammatory genes and may be an important mediator in carcinogenesis. We therefore tagged SNPs in more than 200 genes in the NF-κB pathway for a total of 2,282 SNPs (including rs17561) for genotype analysis of 15,604 cases of ovarian cancer in patients of European descent, including 6,179 of high-grade serous (HGS), 2,100 endometrioid, 1,591 mucinous, 1,034 clear cell, and 1,016 low-grade serous, including 23,235 control cases spanning 40 studies in the Ovarian Cancer Association Consortium. In this large population, we confirmed the association between rs17561 and clear cell ovarian cancer [OR, 0.84; 95% confidence interval (CI), 0.76-0.93; P = 0.00075], which remained intact even after excluding participants in the prior study (OR, 0.85; 95% CI, 0.75-0.95; P = 0.006). Considering a multiple-testing-corrected significance threshold of P < 2.5 × 10(-5), only one other variant, the TNFSF10 SNP rs6785617, was associated significantly with a risk of ovarian cancer (low malignant potential tumors OR, 0.85; 95% CI, 0.79-0.91; P = 0.00002). Our results extend the evidence that borderline tumors may have a distinct genetic etiology. Further investigation of how these SNPs might modify ovarian cancer associations with other inflammation-related risk factors is warranted.
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- 2014
18. Identification of New Genetic Susceptibility Loci for Breast Cancer Through Consideration of Gene‐Environment Interactions
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Schoeps, Anja, Rudolph, Anja, Seibold, Petra, Dunning, Alison M, Milne, Roger L, Bojesen, Stig E, Swerdlow, Anthony, Andrulis, Irene, Brenner, Hermann, Behrens, Sabine, Orr, Nicholas, Jones, Michael, Ashworth, Alan, Li, Jingmei, Cramp, Helen, Connley, Dan, Czene, Kamila, Darabi, Hatef, Chanock, Stephen J, Lissowska, Jolanta, Figueroa, Jonine D, Knight, Julia, Glendon, Gord, Mulligan, Anna M, Dumont, Martine, Severi, Gianluca, Baglietto, Laura, Olson, Janet, Vachon, Celine, Purrington, Kristen, Moisse, Matthieu, Neven, Patrick, Wildiers, Hans, Spurdle, Amanda, Kosma, Veli‐Matti, Kataja, Vesa, Hartikainen, Jaana M, Hamann, Ute, Ko, Yon‐Dschun, Dieffenbach, Aida K, Arndt, Volker, Stegmaier, Christa, Malats, Núria, Perez, José I Arias, Benítez, Javier, Flyger, Henrik, Nordestgaard, Børge G, Truong, Thérèse, Cordina‐Duverger, Emilie, Menegaux, Florence, dos Santos Silva, Isabel, Fletcher, Olivia, Johnson, Nichola, Häberle, Lothar, Beckmann, Matthias W, Ekici, Arif B, Braaf, Linde, Atsma, Femke, Broek, Alexandra J den, Makalic, Enes, Schmidt, Daniel F, Southey, Melissa C, Cox, Angela, Simard, Jacques, Giles, Graham G, Lambrechts, Diether, Mannermaa, Arto, Brauch, Hiltrud, Guénel, Pascal, Peto, Julian, Fasching, Peter A, Hopper, John, Flesch‐Janys, Dieter, Couch, Fergus, Chenevix‐Trench, Georgia, Pharoah, Paul DP, Garcia‐Closas, Montserrat, Schmidt, Marjanka K, Hall, Per, Easton, Douglas F, and Chang‐Claude, Jenny
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Biological Sciences ,Genetics ,Epidemiology ,Health Services and Systems ,Health Sciences ,Genetic Testing ,Human Genome ,Prevention ,Breast Cancer ,Aging ,Clinical Research ,Cancer ,Aetiology ,2.1 Biological and endogenous factors ,Adolescent ,Body Height ,Body Mass Index ,Breast Neoplasms ,Chromosomes ,Human ,Pair 21 ,Chromosomes ,Human ,Pair 6 ,Female ,Gene-Environment Interaction ,Genetic Loci ,Genetic Predisposition to Disease ,Humans ,Linkage Disequilibrium ,Menarche ,Middle Aged ,Parity ,Polymorphism ,Single Nucleotide ,Postmenopause ,White People ,breast cancer risk ,gene-environment interaction ,polymorphisms ,body mass index ,case-control study ,Public Health and Health Services - Abstract
Genes that alter disease risk only in combination with certain environmental exposures may not be detected in genetic association analysis. By using methods accounting for gene-environment (G × E) interaction, we aimed to identify novel genetic loci associated with breast cancer risk. Up to 34,475 cases and 34,786 controls of European ancestry from up to 23 studies in the Breast Cancer Association Consortium were included. Overall, 71,527 single nucleotide polymorphisms (SNPs), enriched for association with breast cancer, were tested for interaction with 10 environmental risk factors using three recently proposed hybrid methods and a joint test of association and interaction. Analyses were adjusted for age, study, population stratification, and confounding factors as applicable. Three SNPs in two independent loci showed statistically significant association: SNPs rs10483028 and rs2242714 in perfect linkage disequilibrium on chromosome 21 and rs12197388 in ARID1B on chromosome 6. While rs12197388 was identified using the joint test with parity and with age at menarche (P-values = 3 × 10(-07)), the variants on chromosome 21 q22.12, which showed interaction with adult body mass index (BMI) in 8,891 postmenopausal women, were identified by all methods applied. SNP rs10483028 was associated with breast cancer in women with a BMI below 25 kg/m(2) (OR = 1.26, 95% CI 1.15-1.38) but not in women with a BMI of 30 kg/m(2) or higher (OR = 0.89, 95% CI 0.72-1.11, P for interaction = 3.2 × 10(-05)). Our findings confirm comparable power of the recent methods for detecting G × E interaction and the utility of using G × E interaction analyses to identify new susceptibility loci.
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- 2014
19. Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia
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Berndt, Sonja I, Skibola, Christine F, Joseph, Vijai, Camp, Nicola J, Nieters, Alexandra, Wang, Zhaoming, Cozen, Wendy, Monnereau, Alain, Wang, Sophia S, Kelly, Rachel S, Lan, Qing, Teras, Lauren R, Chatterjee, Nilanjan, Chung, Charles C, Yeager, Meredith, Brooks-Wilson, Angela R, Hartge, Patricia, Purdue, Mark P, Birmann, Brenda M, Armstrong, Bruce K, Cocco, Pierluigi, Zhang, Yawei, Severi, Gianluca, Zeleniuch-Jacquotte, Anne, Lawrence, Charles, Burdette, Laurie, Yuenger, Jeffrey, Hutchinson, Amy, Jacobs, Kevin B, Call, Timothy G, Shanafelt, Tait D, Novak, Anne J, Kay, Neil E, Liebow, Mark, Wang, Alice H, Smedby, Karin E, Adami, Hans-Olov, Melbye, Mads, Glimelius, Bengt, Chang, Ellen T, Glenn, Martha, Curtin, Karen, Cannon-Albright, Lisa A, Jones, Brandt, Diver, W Ryan, Link, Brian K, Weiner, George J, Conde, Lucia, Bracci, Paige M, Riby, Jacques, Holly, Elizabeth A, Smith, Martyn T, Jackson, Rebecca D, Tinker, Lesley F, Benavente, Yolanda, Becker, Nikolaus, Boffetta, Paolo, Brennan, Paul, Foretova, Lenka, Maynadie, Marc, McKay, James, Staines, Anthony, Rabe, Kari G, Achenbach, Sara J, Vachon, Celine M, Goldin, Lynn R, Strom, Sara S, Lanasa, Mark C, Spector, Logan G, Leis, Jose F, Cunningham, Julie M, Weinberg, J Brice, Morrison, Vicki A, Caporaso, Neil E, Norman, Aaron D, Linet, Martha S, De Roos, Anneclaire J, Morton, Lindsay M, Severson, Richard K, Riboli, Elio, Vineis, Paolo, Kaaks, Rudolph, Trichopoulos, Dimitrios, Masala, Giovanna, Weiderpass, Elisabete, Chirlaque, María-Dolores, Vermeulen, Roel CH, Travis, Ruth C, Giles, Graham G, Albanes, Demetrius, Virtamo, Jarmo, Weinstein, Stephanie, Clavel, Jacqueline, Zheng, Tongzhang, Holford, Theodore R, Offit, Kenneth, Zelenetz, Andrew, Klein, Robert J, Spinelli, John J, and Bertrand, Kimberly A
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Cancer ,Case-Control Studies ,Chromosomes ,Human ,Pair 2 ,Genetic Loci ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Humans ,Leukemia ,Lymphocytic ,Chronic ,B-Cell ,Linkage Disequilibrium ,Polymorphism ,Single Nucleotide ,Recombination ,Genetic ,Risk ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - Abstract
Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P=1.22×10(-14)), 18q21.33 (BCL2, P=7.76×10(-11)), 11p15.5 (C11orf21, P=2.15×10(-10)), 4q25 (LEF1, P=4.24×10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P=2.50×10(-9)), 9p21.3 (CDKN2B-AS1, P=1.27×10(-8)), 18q21.32 (PMAIP1, P=2.51×10(-8)), 15q15.1 (BMF, P=2.71×10(-10)) and 2p22.2 (QPCT, P=1.68×10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P=2.08×10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P=5.40×10(-8)) and 5p15.33 (TERT, P=1.92×10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.
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- 2013
20. Epigenetic analysis leads to identification of HNF1B as a subtype-specific susceptibility gene for ovarian cancer
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Shen, Hui, Fridley, Brooke L, Song, Honglin, Lawrenson, Kate, Cunningham, Julie M, Ramus, Susan J, Cicek, Mine S, Tyrer, Jonathan, Stram, Douglas, Larson, Melissa C, Köbel, Martin, Ziogas, Argyrios, Zheng, Wei, Yang, Hannah P, Wu, Anna H, Wozniak, Eva L, Ling Woo, Yin, Winterhoff, Boris, Wik, Elisabeth, Whittemore, Alice S, Wentzensen, Nicolas, Palmieri Weber, Rachel, Vitonis, Allison F, Vincent, Daniel, Vierkant, Robert A, Vergote, Ignace, Van Den Berg, David, Van Altena, Anne M, Tworoger, Shelley S, Thompson, Pamela J, Tessier, Daniel C, Terry, Kathryn L, Teo, Soo-Hwang, Templeman, Claire, Stram, Daniel O, Southey, Melissa C, Sieh, Weiva, Siddiqui, Nadeem, Shvetsov, Yurii B, Shu, Xiao-Ou, Shridhar, Viji, Wang-Gohrke, Shan, Severi, Gianluca, Schwaab, Ira, Salvesen, Helga B, Rzepecka, Iwona K, Runnebaum, Ingo B, Anne Rossing, Mary, Rodriguez-Rodriguez, Lorna, Risch, Harvey A, Renner, Stefan P, Poole, Elizabeth M, Pike, Malcolm C, Phelan, Catherine M, Pelttari, Liisa M, Pejovic, Tanja, Paul, James, Orlow, Irene, Zawiah Omar, Siti, Olson, Sara H, Odunsi, Kunle, Nickels, Stefan, Nevanlinna, Heli, Ness, Roberta B, Narod, Steven A, Nakanishi, Toru, Moysich, Kirsten B, Monteiro, Alvaro NA, Moes-Sosnowska, Joanna, Modugno, Francesmary, Menon, Usha, McLaughlin, John R, McGuire, Valerie, Matsuo, Keitaro, Mat Adenan, Noor Azmi, Massuger, Leon FAG, Lurie, Galina, Lundvall, Lene, Lubiński, Jan, Lissowska, Jolanta, Levine, Douglas A, Leminen, Arto, Lee, Alice W, Le, Nhu D, Lambrechts, Sandrina, Lambrechts, Diether, Kupryjanczyk, Jolanta, Krakstad, Camilla, Konecny, Gottfried E, Krüger Kjaer, Susanne, Kiemeney, Lambertus A, Kelemen, Linda E, Keeney, Gary L, Karlan, Beth Y, Karevan, Rod, Kalli, Kimberly R, Kajiyama, Hiroaki, Ji, Bu-Tian, Jensen, Allan, and Jakubowska, Anna
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Oncology and Carcinogenesis ,Ovarian Cancer ,Cancer ,Human Genome ,Rare Diseases ,Prevention ,Aetiology ,2.1 Biological and endogenous factors ,DNA Methylation ,Epigenesis ,Genetic ,Female ,Gene Expression Profiling ,Genetic Predisposition to Disease ,Hepatocyte Nuclear Factor 1-beta ,Humans ,Ovarian Neoplasms ,Polymorphism ,Single Nucleotide ,Promoter Regions ,Genetic ,PRACTICAL Consortium ,Australian Ovarian Cancer Study Group ,Australian Cancer Study - Abstract
HNF1B is overexpressed in clear cell epithelial ovarian cancer, and we observed epigenetic silencing in serous epithelial ovarian cancer, leading us to hypothesize that variation in this gene differentially associates with epithelial ovarian cancer risk according to histological subtype. Here we comprehensively map variation in HNF1B with respect to epithelial ovarian cancer risk and analyse DNA methylation and expression profiles across histological subtypes. Different single-nucleotide polymorphisms associate with invasive serous (rs7405776 odds ratio (OR)=1.13, P=3.1 × 10(-10)) and clear cell (rs11651755 OR=0.77, P=1.6 × 10(-8)) epithelial ovarian cancer. Risk alleles for the serous subtype associate with higher HNF1B-promoter methylation in these tumours. Unmethylated, expressed HNF1B, primarily present in clear cell tumours, coincides with a CpG island methylator phenotype affecting numerous other promoters throughout the genome. Different variants in HNF1B associate with risk of serous and clear cell epithelial ovarian cancer; DNA methylation and expression patterns are also notably distinct between these subtypes. These findings underscore distinct mechanisms driving different epithelial ovarian cancer histological subtypes.
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- 2013
21. Stem cell replication, somatic mutations and role of randomness in the development of cancer
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Perduca, Vittorio, Alexandrov, Ludmil B., Kelly-Irving, Michelle, Delpierre, Cyrille, Omichessan, Hanane, Little, Mark P., Vineis, Paolo, and Severi, Gianluca
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- 2019
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22. Genome-wide association study of glioma and meta-analysis
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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
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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.
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- 2012
23. CHEK2*1100delC heterozygosity in women with breast cancer associated with early death, breast cancer-specific death, and increased risk of a second breast cancer.
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Weischer, Maren, Nordestgaard, Børge G, Pharoah, Paul, Bolla, Manjeet K, Nevanlinna, Heli, Van't Veer, Laura J, Garcia-Closas, Montserrat, Hopper, John L, Hall, Per, Andrulis, Irene L, Devilee, Peter, Fasching, Peter A, Anton-Culver, Hoda, Lambrechts, Diether, Hooning, Maartje, Cox, Angela, Giles, Graham G, Burwinkel, Barbara, Lindblom, Annika, Couch, Fergus J, Mannermaa, Arto, Grenaker Alnæs, Grethe, John, Esther M, Dörk, Thilo, Flyger, Henrik, Dunning, Alison M, Wang, Qin, Muranen, Taru A, van Hien, Richard, Figueroa, Jonine, Southey, Melissa C, Czene, Kamila, Knight, Julia A, Tollenaar, Rob AEM, Beckmann, Matthias W, Ziogas, Argyrios, Christiaens, Marie-Rose, Collée, Johanna Margriet, Reed, Malcolm WR, Severi, Gianluca, Marme, Frederik, Margolin, Sara, Olson, Janet E, Kosma, Veli-Matti, Kristensen, Vessela N, Miron, Alexander, Bogdanova, Natalia, Shah, Mitul, Blomqvist, Carl, Broeks, Annegien, Sherman, Mark, Phillips, Kelly-Anne, Li, Jingmei, Liu, Jianjun, Glendon, Gord, Seynaeve, Caroline, Ekici, Arif B, Leunen, Karin, Kriege, Mieke, Cross, Simon S, Baglietto, Laura, Sohn, Christof, Wang, Xianshu, Kataja, Vesa, Børresen-Dale, Anne-Lise, Meyer, Andreas, Easton, Douglas F, Schmidt, Marjanka K, and Bojesen, Stig E
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Humans ,Breast Neoplasms ,Neoplasms ,Second Primary ,Genetic Predisposition to Disease ,Prognosis ,Case-Control Studies ,Prospective Studies ,Genotype ,Heterozygote ,Germ-Line Mutation ,Middle Aged ,Female ,Checkpoint Kinase 2 ,Protein Serine-Threonine Kinases ,Breast Cancer ,Clinical Research ,Cancer ,Prevention ,Genetics ,Estrogen ,Clinical Sciences ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
PurposeWe tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer-specific death, and risk of a second breast cancer in women with a first breast cancer.Patients and methodsFrom 22 studies participating in the Breast Cancer Association Consortium, 25,571 white women with invasive breast cancer were genotyped for CHEK2*1100delC and observed for up to 20 years (median, 6.6 years). We examined risk of early death and breast cancer-specific death by estrogen receptor status and risk of a second breast cancer after a first breast cancer in prospective studies.ResultsCHEK2*1100delC heterozygosity was found in 459 patients (1.8%). In women with estrogen receptor-positive breast cancer, multifactorially adjusted hazard ratios for heterozygotes versus noncarriers were 1.43 (95% CI, 1.12 to 1.82; log-rank P = .004) for early death and 1.63 (95% CI, 1.24 to 2.15; log-rank P < .001) for breast cancer-specific death. In all women, hazard ratio for a second breast cancer was 2.77 (95% CI, 2.00 to 3.83; log-rank P < .001) increasing to 3.52 (95% CI, 2.35 to 5.27; log-rank P < .001) in women with estrogen receptor-positive first breast cancer only.ConclusionAmong women with estrogen receptor-positive breast cancer, CHEK2*1100delC heterozygosity was associated with a 1.4-fold risk of early death, a 1.6-fold risk of breast cancer-specific death, and a 3.5-fold risk of a second breast cancer. This is one of the few examples of a genetic factor that influences long-term prognosis being documented in an extensive series of women with breast cancer.
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- 2012
24. Breast Cancer Risk and 6q22.33: Combined Results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2
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Kirchhoff, Tomas, Gaudet, Mia M, Antoniou, Antonis C, McGuffog, Lesley, Humphreys, Manjeet K, Dunning, Alison M, Bojesen, Stig E, Nordestgaard, Børge G, Flyger, Henrik, Kang, Daehee, Yoo, Keun-Young, Noh, Dong-Young, Ahn, Sei-Hyun, Dork, Thilo, Schürmann, Peter, Karstens, Johann H, Hillemanns, Peter, Couch, Fergus J, Olson, Janet, Vachon, Celine, Wang, Xianshu, Cox, Angela, Brock, Ian, Elliott, Graeme, Reed, Malcolm WR, Burwinkel, Barbara, Meindl, Alfons, Brauch, Hiltrud, Hamann, Ute, Ko, Yon-Dschun, Broeks, Annegien, Schmidt, Marjanka K, Van ‘t Veer, Laura J, Braaf, Linde M, Johnson, Nichola, Fletcher, Olivia, Gibson, Lorna, Peto, Julian, Turnbull, Clare, Seal, Sheila, Renwick, Anthony, Rahman, Nazneen, Wu, Pei-Ei, Yu, Jyh-Cherng, Hsiung, Chia-Ni, Shen, Chen-Yang, Southey, Melissa C, Hopper, John L, Hammet, Fleur, Van Dorpe, Thijs, Dieudonne, Anne-Sophie, Hatse, Sigrid, Lambrechts, Diether, Andrulis, Irene L, Bogdanova, Natalia, Antonenkova, Natalia, Rogov, Juri I, Prokofieva, Daria, Bermisheva, Marina, Khusnutdinova, Elza, van Asperen, Christi J, Tollenaar, Robert AEM, Hooning, Maartje J, Devilee, Peter, Margolin, Sara, Lindblom, Annika, Milne, Roger L, Arias, José Ignacio, Zamora, M Pilar, Benítez, Javier, Severi, Gianluca, Baglietto, Laura, Giles, Graham G, kConFab, Group, AOCS Study, Spurdle, Amanda B, Beesley, Jonathan, Chen, Xiaoqing, Holland, Helene, Healey, Sue, Wang-Gohrke, Shan, Chang-Claude, Jenny, Mannermaa, Arto, Kosma, Veli-Matti, Kauppinen, Jaana, Kataja, Vesa, Agnarsson, Bjarni A, Caligo, Maria A, Godwin, Andrew K, Nevanlinna, Heli, Heikkinen, Tuomas, Fredericksen, Zachary, Lindor, Noralane, Nathanson, Katherine L, Domchek, Susan M, SWE-BRCA, Loman, Niklas, Karlsson, Per, Askmalm, Marie Stenmark, and Melin, Beatrice
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Health Services and Systems ,Biomedical and Clinical Sciences ,Health Sciences ,Oncology and Carcinogenesis ,Cancer ,Genetics ,Breast Cancer ,2.1 Biological and endogenous factors ,Aetiology ,Alleles ,BRCA1 Protein ,BRCA2 Protein ,Breast Neoplasms ,Chromosomes ,Human ,Pair 6 ,Confidence Intervals ,Female ,Genetic Association Studies ,Genetic Predisposition to Disease ,Heterozygote ,Humans ,Middle Aged ,Odds Ratio ,Polymorphism ,Single Nucleotide ,Proportional Hazards Models ,Receptors ,Estrogen ,Risk Factors ,GENICA Network ,kConFab ,AOCS Study Group ,SWE-BRCA ,HEBON ,EMBRACE ,BCAC/CIMBA ,General Science & Technology - Abstract
Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I(2) = 49.3%; p =
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- 2012
25. 7q21-rs6964587 and breast cancer risk: an extended case–control study by the Breast Cancer Association Consortium
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Milne, Roger L, Lorenzo-Bermejo, Justo, Burwinkel, Barbara, Malats, Núria, Arias, Jose Ignacio, Zamora, M Pilar, Benítez, Javier, Humphreys, Manjeet K, García-Closas, Montserrat, Chanock, Stephen J, Lissowska, Jolanta, Sherman, Mark E, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, Nevanlinna, Heli, Heikkinen, Tuomas, Aittomäki, Kristiina, Blomqvist, Carl, Anton-Culver, Hoda, Ziogas, Argyrios, Devilee, Peter, van Asperen, Christie J, Tollenaar, Rob AEM, Seynaeve, Caroline, Hall, Per, Czene, Kamila, Liu, Jianjun, Irwanto, Astrid K, Kang, Daehee, Yoo, Keun-Young, Noh, Dong-Young, Couch, Fergus J, Olson, Janet E, Wang, Xianshu, Fredericksen, Zachary, Nordestgaard, Børge G, Bojesen, Stig E, Flyger, Henrik, Margolin, Sara, Lindblom, Annika, Fasching, Peter A, Schulz-Wendtland, Ruediger, Ekici, Arif B, Beckmann, Matthias W, Wang-Gohrke, Shan, Shen, Chen-Yang, Yu, Jyh-Cherng, Hsu, Huan-Ming, Wu, Pei-Ei, Giles, Graham G, Severi, Gianluca, Baglietto, Laura, English, Dallas R, Cox, Angela, Brock, Ian, Elliott, Graeme, Reed, Malcolm WR, Beesley, Jonathan, Chen, Xiaoqing, Investigators, kConFab, Group, AOCS, Fletcher, Olivia, Gibson, Lorna, dos Santos Silva, Isabel, Peto, Julian, Frank, Bernd, Heil, Joerg, Meindl, Alfons, Chang-Claude, Jenny, Hein, Rebecca, Vrieling, Alina, Flesch-Janys, Dieter, Southey, Melissa C, Smith, Letitia, Apicella, Carmel, Hopper, John L, Dunning, Alison M, Pooley, Karen A, Pharoah, Paul DP, Hamann, Ute, Pesch, Beate, Ko, Yon-Dschun, Network, The GENICA, Easton, Douglas F, and Chenevix-Trench, Georgia
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Biological Sciences ,Biomedical and Clinical Sciences ,Genetics ,Oncology and Carcinogenesis ,Breast Cancer ,Clinical Research ,Cancer ,Aetiology ,2.1 Biological and endogenous factors ,A Kinase Anchor Proteins ,Alleles ,Asian People ,Breast Neoplasms ,Case-Control Studies ,Chromosomes ,Human ,Pair 7 ,Cytoskeletal Proteins ,Female ,Genes ,Recessive ,Genetic Predisposition to Disease ,Humans ,Logistic Models ,Odds Ratio ,Polymorphism ,Single Nucleotide ,Risk Factors ,White People ,AOCS Group ,GENICA Network ,Medical and Health Sciences ,Genetics & Heredity ,Clinical sciences - Abstract
BackgroundUsing the Breast Cancer Association Consortium, the authors previously reported that the single nucleotide polymorphism 7q21-rs6964587 (AKAP9-M463I) is associated with breast cancer risk. The authors have now assessed this association more comprehensively using 16 independent case-control studies.MethodsThe authors genotyped 14,843 invasive case patients and 19,852 control subjects with white European ancestry and 2595 invasive case patients and 2192 control subjects with Asian ancestry. ORs were estimated by logistic regression, adjusted for study. Heterogeneity in ORs was assessed by fitting interaction terms or by subclassifying case patients and applying polytomous logistic regression.ResultsFor white European women, the minor T allele of 7q21-rs6964587 was associated with breast cancer risk under a recessive model (OR 1.07, 95% CI 1.00 to 1.13, p = 0.04). Results were inconclusive for Asian women. From a combined analysis of 24 154 case patients and 33,376 control subjects of white European ancestry from the present and previous series, the best-fitting model was recessive, with an estimated OR of 1.08 (95% CI 1.03 to 1.13, p = 0.001). The OR was greater at younger ages (p trend = 0.01).ConclusionThis may be the first common susceptibility allele for breast cancer to be identified with a recessive mode of inheritance.
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- 2011
26. Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies.
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Yang, Xiaohong R, Chang-Claude, Jenny, Goode, Ellen L, Couch, Fergus J, Nevanlinna, Heli, Milne, Roger L, Gaudet, Mia, Schmidt, Marjanka K, Broeks, Annegien, Cox, Angela, Fasching, Peter A, Hein, Rebecca, Spurdle, Amanda B, Blows, Fiona, Driver, Kristy, Flesch-Janys, Dieter, Heinz, Judith, Sinn, Peter, Vrieling, Alina, Heikkinen, Tuomas, Aittomäki, Kristiina, Heikkilä, Päivi, Blomqvist, Carl, Lissowska, Jolanta, Peplonska, Beata, Chanock, Stephen, Figueroa, Jonine, Brinton, Louise, Hall, Per, Czene, Kamila, Humphreys, Keith, Darabi, Hatef, Liu, Jianjun, Van 't Veer, Laura J, van Leeuwen, Flora E, Andrulis, Irene L, Glendon, Gord, Knight, Julia A, Mulligan, Anna Marie, O'Malley, Frances P, Weerasooriya, Nayana, John, Esther M, Beckmann, Matthias W, Hartmann, Arndt, Weihbrecht, Sebastian B, Wachter, David L, Jud, Sebastian M, Loehberg, Christian R, Baglietto, Laura, English, Dallas R, Giles, Graham G, McLean, Catriona A, Severi, Gianluca, Lambrechts, Diether, Vandorpe, Thijs, Weltens, Caroline, Paridaens, Robert, Smeets, Ann, Neven, Patrick, Wildiers, Hans, Wang, Xianshu, Olson, Janet E, Cafourek, Victoria, Fredericksen, Zachary, Kosel, Matthew, Vachon, Celine, Cramp, Helen E, Connley, Daniel, Cross, Simon S, Balasubramanian, Sabapathy P, Reed, Malcolm WR, Dörk, Thilo, Bremer, Michael, Meyer, Andreas, Karstens, Johann H, Ay, Aysun, Park-Simon, Tjoung-Won, Hillemanns, Peter, Arias Pérez, Jose Ignacio, Menéndez Rodríguez, Primitiva, Zamora, Pilar, Benítez, Javier, Ko, Yon-Dschun, Fischer, Hans-Peter, Hamann, Ute, Pesch, Beate, Brüning, Thomas, Justenhoven, Christina, Brauch, Hiltrud, Eccles, Diana M, Tapper, William J, Gerty, Sue M, Sawyer, Elinor J, Tomlinson, Ian P, Jones, Angela, Kerin, Michael, Miller, Nicola, McInerney, Niall, Anton-Culver, Hoda, and Ziogas, Argyrios
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Humans ,Breast Neoplasms ,Obesity ,Receptor ,erbB-2 ,Receptors ,Estrogen ,Receptors ,Progesterone ,Body Mass Index ,Logistic Models ,Odds Ratio ,Risk Factors ,Case-Control Studies ,Age Factors ,Parity ,Parturition ,Menarche ,Female ,Keratin-5 ,ErbB Receptors ,Biomarkers ,Tumor ,Receptor ,ErbB-2 ,Prevention ,Cancer ,Aging ,Breast Cancer ,Clinical Research ,Aetiology ,2.1 Biological and endogenous factors ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
BackgroundPrevious studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors.MethodsWe pooled tumor marker and epidemiological risk factor data from 35,568 invasive breast cancer case patients from 34 studies participating in the Breast Cancer Association Consortium. Logistic regression models were used in case-case analyses to estimate associations between epidemiological risk factors and tumor subtypes, and case-control analyses to estimate associations between epidemiological risk factors and the risk of developing specific tumor subtypes in 12 population-based studies. All statistical tests were two-sided.ResultsIn case-case analyses, of the epidemiological risk factors examined, early age at menarche (≤12 years) was less frequent in case patients with PR(-) than PR(+) tumors (P = .001). Nulliparity (P = 3 × 10(-6)) and increasing age at first birth (P = 2 × 10(-9)) were less frequent in ER(-) than in ER(+) tumors. Obesity (body mass index [BMI] ≥ 30 kg/m(2)) in younger women (≤50 years) was more frequent in ER(-)/PR(-) than in ER(+)/PR(+) tumors (P = 1 × 10(-7)), whereas obesity in older women (>50 years) was less frequent in PR(-) than in PR(+) tumors (P = 6 × 10(-4)). The triple-negative (ER(-)/PR(-)/HER2(-)) or core basal phenotype (CBP; triple-negative and cytokeratins [CK]5/6(+) and/or epidermal growth factor receptor [EGFR](+)) accounted for much of the heterogeneity in parity-related variables and BMI in younger women. Case-control analyses showed that nulliparity, increasing age at first birth, and obesity in younger women showed the expected associations with the risk of ER(+) or PR(+) tumors but not triple-negative (nulliparity vs parity, odds ratio [OR] = 0.94, 95% confidence interval [CI] = 0.75 to 1.19, P = .61; 5-year increase in age at first full-term birth, OR = 0.95, 95% CI = 0.86 to 1.05, P = .34; obesity in younger women, OR = 1.36, 95% CI = 0.95 to 1.94, P = .09) or CBP tumors.ConclusionsThis study shows that reproductive factors and BMI are most clearly associated with hormone receptor-positive tumors and suggest that triple-negative or CBP tumors may have distinct etiology.
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- 2011
27. Association Between a Germline OCA2 Polymorphism at Chromosome 15q13.1 and Estrogen Receptor–Negative Breast Cancer Survival
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Azzato, Elizabeth M, Tyrer, Jonathan, Fasching, Peter A, Beckmann, Matthias W, Ekici, Arif B, Schulz-Wendtland, Rüdiger, Bojesen, Stig E, Nordestgaard, Børge G, Flyger, Henrik, Milne, Roger L, Arias, José Ignacio, Menéndez, Primitiva, Benítez, Javier, Chang-Claude, Jenny, Hein, Rebecca, Wang-Gohrke, Shan, Nevanlinna, Heli, Heikkinen, Tuomas, Aittomäki, Kristiina, Blomqvist, Carl, Margolin, Sara, Mannermaa, Arto, Kosma, Veli-Matti, Kataja, Vesa, Beesley, Jonathan, Chen, Xiaoqing, Chenevix-Trench, Georgia, Couch, Fergus J, Olson, Janet E, Fredericksen, Zachary S, Wang, Xianshu, Giles, Graham G, Severi, Gianluca, Baglietto, Laura, Southey, Melissa C, Devilee, Peter, Tollenaar, Rob AEM, Seynaeve, Caroline, García-Closas, Montserrat, Lissowska, Jolanta, Sherman, Mark E, Bolton, Kelly L, Hall, Per, Czene, Kamila, Cox, Angela, Brock, Ian W, Elliott, Graeme C, Reed, Malcolm WR, Greenberg, David, Anton-Culver, Hoda, Ziogas, Argyrios, Humphreys, Manjeet, Easton, Douglas F, Caporaso, Neil E, and Pharoah, Paul DP
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Prevention ,Genetics ,Breast Cancer ,Human Genome ,Cancer ,Adult ,Aged ,Alleles ,Biomarkers ,Tumor ,Breast Neoplasms ,Chromosomes ,Human ,Pair 15 ,Female ,Genotype ,Germ-Line Mutation ,Humans ,Membrane Transport Proteins ,Middle Aged ,Polymorphism ,Single Nucleotide ,Proportional Hazards Models ,Receptors ,Estrogen ,Research Design ,Risk Assessment ,Risk Factors ,Survival Analysis ,Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BackgroundTraditional prognostic factors for survival and treatment response of patients with breast cancer do not fully account for observed survival variation. We used available genotype data from a previously conducted two-stage, breast cancer susceptibility genome-wide association study (ie, Studies of Epidemiology and Risk factors in Cancer Heredity [SEARCH]) to investigate associations between variation in germline DNA and overall survival.MethodsWe evaluated possible associations between overall survival after a breast cancer diagnosis and 10 621 germline single-nucleotide polymorphisms (SNPs) from up to 3761 patients with invasive breast cancer (including 647 deaths and 26 978 person-years at risk) that were genotyped previously in the SEARCH study with high-density oligonucleotide microarrays (ie, hypothesis-generating set). Associations with all-cause mortality were assessed for each SNP by use of Cox regression analysis, generating a per rare allele hazard ratio (HR). To validate putative associations, we used patient genotype information that had been obtained with 5' nuclease assay or mass spectrometry and overall survival information for up to 14 096 patients with invasive breast cancer (including 2303 deaths and 70 019 person-years at risk) from 15 international case-control studies (ie, validation set). Fixed-effects meta-analysis was used to generate an overall effect estimate in the validation dataset and in combined SEARCH and validation datasets. All statistical tests were two-sided.ResultsIn the hypothesis-generating dataset, SNP rs4778137 (C>G) of the OCA2 gene at 15q13.1 was statistically significantly associated with overall survival among patients with estrogen receptor-negative tumors, with the rare G allele being associated with increased overall survival (HR of death per rare allele carried = 0.56, 95% confidence interval [CI] = 0.41 to 0.75, P = 9.2 x 10(-5)). This association was also observed in the validation dataset (HR of death per rare allele carried = 0.88, 95% CI = 0.78 to 0.99, P = .03) and in the combined dataset (HR of death per rare allele carried = 0.82, 95% CI = 0.73 to 0.92, P = 5 x 10(-4)).ConclusionThe rare G allele of the OCA2 polymorphism, rs4778137, may be associated with improved overall survival among patients with estrogen receptor-negative breast cancer.
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- 2010
28. Risk of Estrogen Receptor–Positive and –Negative Breast Cancer and Single–Nucleotide Polymorphism 2q35-rs13387042
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Milne, Roger L, Benítez, Javier, Nevanlinna, Heli, Heikkinen, Tuomas, Aittomäki, Kristiina, Blomqvist, Carl, Arias, José Ignacio, Zamora, M Pilar, Burwinkel, Barbara, Bartram, Claus R, Meindl, Alfons, Schmutzler, Rita K, Cox, Angela, Brock, Ian, Elliott, Graeme, Reed, Malcolm WR, Southey, Melissa C, Smith, Letitia, Spurdle, Amanda B, Hopper, John L, Couch, Fergus J, Olson, Janet E, Wang, Xianshu, Fredericksen, Zachary, Schürmann, Peter, Bremer, Michael, Hillemanns, Peter, Dörk, Thilo, Devilee, Peter, van Asperen, Christie J, Tollenaar, Rob AEM, Seynaeve, Caroline, Hall, Per, Czene, Kamila, Liu, Jianjun, Li, Yuqing, Ahmed, Shahana, Dunning, Alison M, Maranian, Melanie, Pharoah, Paul DP, Chenevix-Trench, Georgia, Beesley, Jonathan, Investigators, kConFab, Group, AOCS, Bogdanova, Natalia V, Antonenkova, Natalia N, Zalutsky, Iosif V, Anton-Culver, Hoda, Ziogas, Argyrios, Brauch, Hiltrud, Justenhoven, Christina, Ko, Yon-Dschun, Haas, Susanne, Fasching, Peter A, Strick, Reiner, Ekici, Arif B, Beckmann, Matthias W, Giles, Graham G, Severi, Gianluca, Baglietto, Laura, English, Dallas R, Fletcher, Olivia, Johnson, Nichola, dos Santos Silva, Isabel, Peto, Julian, Turnbull, Clare, Hines, Sarah, Renwick, Anthony, Rahman, Nazneen, Nordestgaard, Børge G, Bojesen, Stig E, Flyger, Henrik, Kang, Daehee, Yoo, Keun-Young, Noh, Dong-Young, Mannermaa, Arto, Kataja, Vesa, Kosma, Veli-Matti, García-Closas, Montserrat, Chanock, Stephen, Lissowska, Jolanta, Brinton, Louise A, Chang-Claude, Jenny, Wang-Gohrke, Shan, Shen, Chen-Yang, Wang, Hui-Chun, Yu, Jyh-Cherng, Chen, Sou-Tong, Bermisheva, Marina, Nikolaeva, Tatjana, Khusnutdinova, Elza, Humphreys, Manjeet K, Morrison, Jonathan, Platte, Radka, Easton, Douglas F, and Consortium, on behalf of the Breast Cancer Association
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Genetics ,Breast Cancer ,Clinical Research ,Cancer ,Human Genome ,Estrogen ,Adult ,Aged ,Asian People ,Biomarkers ,Tumor ,Breast Neoplasms ,Carcinoma ,Ductal ,Breast ,Carcinoma ,Intraductal ,Noninfiltrating ,Case-Control Studies ,Confidence Intervals ,Confounding Factors ,Epidemiologic ,Female ,Gene Frequency ,Genetic Predisposition to Disease ,Genotype ,Humans ,Linkage Disequilibrium ,Middle Aged ,Neoplasms ,Hormone-Dependent ,Odds Ratio ,Polymorphism ,Single Nucleotide ,Receptors ,Estrogen ,Receptors ,Progesterone ,White People ,kConFab Investigators ,AOCS Group ,Breast Cancer Association Consortium ,Oncology & Carcinogenesis ,Oncology and carcinogenesis - Abstract
BackgroundA recent genome-wide association study identified single-nucleotide polymorphism (SNP) 2q35-rs13387042 as a marker of susceptibility to estrogen receptor (ER)-positive breast cancer. We attempted to confirm this association using the Breast Cancer Association Consortium.Methods2q35-rs13387042 SNP was genotyped for 31 510 women with invasive breast cancer, 1101 women with ductal carcinoma in situ, and 35 969 female control subjects from 25 studies. Odds ratios (ORs) were estimated by logistic regression, adjusted for study. Heterogeneity in odds ratios by each of age, ethnicity, and study was assessed by fitting interaction terms. Heterogeneity by each of invasiveness, family history, bilaterality, and hormone receptor status was assessed by subclassifying case patients and applying polytomous logistic regression. All statistical tests were two-sided.ResultsWe found strong evidence of association between rs13387042 and breast cancer in white women of European origin (per-allele OR = 1.12, 95% confidence interval [CI] = 1.09 to 1.15; P(trend) = 1.0 x 10(-19)). The odds ratio was lower than that previously reported (P = .02) and did not vary by age or ethnicity (all P > or = .2). However, it was higher when the analysis was restricted to case patients who were selected for a strong family history (P = .02). An association was observed for both ER-positive (OR = 1.14, 95% CI = 1.10 to 1.17; P = 10(-15)) and ER-negative disease (OR = 1.10, 95% CI = 1.04 to 1.15; P = .0003) and both progesterone receptor (PR)-positive (OR = 1.15, 95% CI = 1.11 to 1.19; P = 5 x 10(-14)) and PR-negative disease (OR = 1.10, 95% CI = 1.06 to 1.15; P = .00002).ConclusionThe rs13387042 is associated with both ER-positive and ER-negative breast cancer in European women.
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- 2009
29. Association of ESR1 gene tagging SNPs with breast cancer risk
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Dunning, Alison M, Healey, Catherine S, Baynes, Caroline, Maia, Ana-Teresa, Scollen, Serena, Vega, Ana, Rodríguez, Raquel, Barbosa-Morais, Nuno L, Ponder, Bruce AJ, Low, Yen-Ling, Bingham, Sheila, Haiman, Christopher A, Le Marchand, Loic, Broeks, Annegien, Schmidt, Marjanka K, Hopper, John, Southey, Melissa, Beckmann, Matthias W, Fasching, Peter A, Peto, Julian, Johnson, Nichola, Bojesen, Stig E, Nordestgaard, Børge, Milne, Roger L, Benitez, Javier, Hamann, Ute, Ko, Yon, Schmutzler, Rita K, Burwinkel, Barbara, Schürmann, Peter, Dörk, Thilo, Heikkinen, Tuomas, Nevanlinna, Heli, Lindblom, Annika, Margolin, Sara, Mannermaa, Arto, Kosma, Veli-Matti, Chen, Xiaoqing, Spurdle, Amanda, Change-Claude, Jenny, Flesch-Janys, Dieter, Couch, Fergus J, Olson, Janet E, Severi, Gianluca, Baglietto, Laura, Børresen-Dale, Anne-Lise, Kristensen, Vessela, Hunter, David J, Hankinson, Susan E, Devilee, Peter, Vreeswijk, Maaike, Lissowska, Jolanta, Brinton, Louise, Liu, Jianjun, Hall, Per, Kang, Daehee, Yoo, Keun-Young, Shen, Chen-Yang, Yu, Jyh-Cherng, Anton-Culver, Hoda, Ziogoas, Argyrios, Sigurdson, Alice, Struewing, Jeff, Easton, Douglas F, Garcia-Closas, Montserrat, Humphreys, Manjeet K, Morrison, Jonathan, Pharoah, Paul DP, Pooley, Karen A, and Chenevix-Trench, Georgia
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Genetics ,Cancer ,Breast Cancer ,Prevention ,Clinical Research ,2.1 Biological and endogenous factors ,Aetiology ,Breast Neoplasms ,Estrogen Receptor alpha ,Female ,Genetic Predisposition to Disease ,Haplotypes ,Humans ,Neoplasm Staging ,Polymorphism ,Single Nucleotide ,RNA ,Neoplasm ,SEARCH ,EPIC ,MEC ,ABCS ,ABCFS ,BBCC ,BBCS ,CGPS ,CNIO-BCS ,GENICA ,GC-HBOC ,HABCS ,HEBCS ,KARBAC ,KBCS ,kConFab and the AOCS Management Group ,MARIE ,for MCBCS ,MCCS ,NBCS ,NHS ,ORIGO ,PBCS ,SASBAC ,SEBCS ,TWBCS ,UCIBCS ,USRTS ,BCAC ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
We have conducted a three-stage, comprehensive single nucleotide polymorphism (SNP)-tagging association study of ESR1 gene variants (SNPs) in more than 55,000 breast cancer cases and controls from studies within the Breast Cancer Association Consortium (BCAC). No large risks or highly significant associations were revealed. SNP rs3020314, tagging a region of ESR1 intron 4, is associated with an increase in breast cancer susceptibility with a dominant mode of action in European populations. Carriers of the c-allele have an odds ratio (OR) of 1.05 [95% Confidence Intervals (CI) 1.02-1.09] relative to t-allele homozygotes, P = 0.004. There is significant heterogeneity between studies, P = 0.002. The increased risk appears largely confined to oestrogen receptor-positive tumour risk. The region tagged by SNP rs3020314 contains sequence that is more highly conserved across mammalian species than the rest of intron 4, and it may subtly alter the ratio of two mRNA splice forms.
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- 2009
30. Circulating bilirubin levels and risk of colorectal cancer: serological and Mendelian randomization analyses
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Seyed Khoei, Nazlisadat, Jenab, Mazda, Murphy, Neil, Banbury, Barbara L., Carreras-Torres, Robert, Viallon, Vivian, Kühn, Tilman, Bueno-de-Mesquita, Bas, Aleksandrova, Krasimira, Cross, Amanda J., Weiderpass, Elisabete, Stepien, Magdalena, Bulmer, Andrew, Tjønneland, Anne, Boutron-Ruault, Marie-Christine, Severi, Gianluca, Carbonnel, Franck, Katzke, Verena, Boeing, Heiner, Bergmann, Manuela M., Trichopoulou, Antonia, Karakatsani, Anna, Martimianaki, Georgia, Palli, Domenico, Tagliabue, Giovanna, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Skeie, Guri, Merino, Susana, Bonet, Catalina, Rodríguez-Barranco, Miguel, Gil, Leire, Chirlaque, Maria-Dolores, Ardanaz, Eva, Myte, Robin, Hultdin, Johan, Perez-Cornago, Aurora, Aune, Dagfinn, Tsilidis, Konstantinos K., Albanes, Demetrius, Baron, John A., Berndt, Sonja I., Bézieau, Stéphane, Brenner, Hermann, Campbell, Peter T., Casey, Graham, Chan, Andrew T., Chang-Claude, Jenny, Chanock, Stephen J., Cotterchio, Michelle, Gallinger, Steven, Gruber, Stephen B., Haile, Robert W., Hampe, Jochen, Hoffmeister, Michael, Hopper, John L., Hsu, Li, Huyghe, Jeroen R., Jenkins, Mark A., Joshi, Amit D., Kampman, Ellen, Larsson, Susanna C., Le Marchand, Loic, Li, Christopher I., Li, Li, Lindblom, Annika, Lindor, Noralane M., Martín, Vicente, Moreno, Victor, Newcomb, Polly A., Offit, Kenneth, Ogino, Shuji, Parfrey, Patrick S., Pharoah, Paul D. P., Rennert, Gad, Sakoda, Lori C., Schafmayer, Clemens, Schmit, Stephanie L., Schoen, Robert E., Slattery, Martha L., Thibodeau, Stephen N., Ulrich, Cornelia M., van Duijnhoven, Franzel J. B., Weigl, Korbinian, Weinstein, Stephanie J., White, Emily, Wolk, Alicja, Woods, Michael O., Wu, Anna H., Zhang, Xuehong, Ferrari, Pietro, Anton, Gabriele, Peters, Annette, Peters, Ulrike, Gunter, Marc J., Wagner, Karl-Heinz, and Freisling, Heinz
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- 2020
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31. Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases: a multinational cohort study
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Freisling, Heinz, Viallon, Vivian, Lennon, Hannah, Bagnardi, Vincenzo, Ricci, Cristian, Butterworth, Adam S., Sweeting, Michael, Muller, David, Romieu, Isabelle, Bazelle, Pauline, Kvaskoff, Marina, Arveux, Patrick, Severi, Gianluca, Bamia, Christina, Kühn, Tilman, Kaaks, Rudolf, Bergmann, Manuela, Boeing, Heiner, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Dahm, Christina C., Menéndez, Virginia, Agudo, Antonio, Sánchez, Maria-Jose, Amiano, Pilar, Santiuste, Carmen, Gurrea, Aurelio Barricarte, Tong, Tammy Y. N., Schmidt, Julie A., Tzoulaki, Ioanna, Tsilidis, Konstantinos K., Ward, Heather, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Picavet, H. Susan J., Bakker, Marije, Monninkhof, Evelyn, Nilsson, Peter, Manjer, Jonas, Rolandsson, Olov, Thysell, Elin, Weiderpass, Elisabete, Jenab, Mazda, Riboli, Elio, Vineis, Paolo, Danesh, John, Wareham, Nick J., Gunter, Marc J., and Ferrari, Pietro
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- 2020
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32. Development and performance evaluation of a GIS-based metric to assess exposure to airborne pollutant emissions from industrial sources
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Coudon, Thomas, Danjou, Aurélie Marcelle Nicole, Faure, Elodie, Praud, Delphine, Severi, Gianluca, Mancini, Francesca Romana, Salizzoni, Pietro, and Fervers, Béatrice
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- 2019
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33. The influence of obesity-related factors in the etiology of renal cell carcinoma-A mendelian randomization study
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Johansson, Mattias, Carreras-Torres, Robert, Scelo, Ghislaine, Purdue, Mark P., Mariosa, Daniela, Muller, David C., Timpson, Nicolas J., Haycock, Philip C., Brown, Kevin M., Wang, Zhaoming, Ye, Yuanqing, Hofmann, Jonathan N., Foll, Matthieu, Gaborieau, Valerie, Machiela, Mitchell J., Colli, Leandro M., Li, Peng, Garnier, Jean-Guillaume, Blanche, Helene, Boland, Anne, Burdette, Laurie, Prokhortchouk, Egor, Skryabin, Konstantin G., Yeager, Meredith, Radojevic-Skodric, Sanja, Ognjanovic, Simona, Foretova, Lenka, Holcatova, Ivana, Janout, Vladimir, Mates, Dana, Mukeriya, Anush, Rascu, Stefan, Zaridze, David, Bencko, Vladimir, Cybulski, Cezary, Fabianova, Eleonora, Jinga, Viorel, Lissowska, Jolanta, Lubinski, Jan, Navratilova, Marie, Rudnai, Peter, Benhamou, Simone, Cancel-Tassin, Geraldine, Cussenot, Olivier, Weiderpass, Elisabete, Ljungberg, Börje, Tumkur Sitaram, Raviprakash, Häggström, Christel, Bruinsma, Fiona, Jordan, Susan J., Severi, Gianluca, Winship, Ingrid, Hveem, Kristian, Vatten, Lars J., Fletcher, Tony, Larsson, Susanna C., Wolk, Alicja, Banks, Rosamonde E., Selby, Peter J., Easton, Douglas F., Andreotti, Gabriella, Beane Freeman, Laura E., Koutros, Stella, Männistö, Satu, Weinstein, Stephanie, Clark, Peter E., Edwards, Todd L., Lipworth, Loren, Gapstur, Susan M., Stevens, Victoria L., Carol, Hallie, Freedman, Matthew L., Pomerantz, Mark M., Cho, Eunyoung, Wilson, Kathryn M., Gaziano, J. Michael, Sesso, Howard D., Freedman, Neal D., Parker, Alexander S., Eckel-Passow, Jeanette E., Huang, Wen-Yi, Kahnoski, Richard J., Lane, Brian R., Noyes, Sabrina L., Petillo, David, Teh, Bin Tean, Peters, Ulrike, White, Emily, Anderson, Garnet L., Johnson, Lisa, Luo, Juhua, Buring, Julie, Lee, I-Min, Chow, Wong-Ho, Moore, Lee E., Eisen, Timothy, Henrion, Marc, Larkin, James, Barman, Poulami, Leibovich, Bradley C., Choueiri, Toni K., Lathrop, G. Mark, Deleuze, Jean-Francois, Gunter, Marc, McKay, James D., Wu, Xifeng, Houlston, Richard S., Chanock, Stephen J., Relton, Caroline, Richards, J. Brent, Martin, Richard M., Davey Smith, George, and Brennan, Paul
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Obesity -- Genetic aspects -- Complications and side effects ,Renal cell carcinoma -- Genetic aspects -- Development and progression -- Care and treatment ,Genetic markers -- Health aspects ,Etiology (Medicine) ,Genetics ,Carcinoma ,Cancer ,Type 2 diabetes ,Genomics ,Insulin ,Proxy ,Lipids ,Genomes ,Fasting ,Glucose ,Biological sciences - Abstract
Background Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation. Methods and findings Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (OR.sub.SD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (OR.sub.SD : 1.56, 95% confidence interval [CI] 1.44-1.70), with comparable results for waist-to-hip ratio (OR.sub.SD : 1.63, 95% CI 1.40-1.90) and body fat percentage (OR.sub.SD : 1.66, 95% CI 1.44-1.90). This analysis further indicated that higher fasting insulin (OR.sub.SD : 1.82, 95% CI 1.30-2.55) and diastolic blood pressure (DBP; OR.sub.SD : 1.28, 95% CI 1.11-1.47), but not systolic blood pressure (OR.sub.SD : 0.98, 95% CI 0.84-1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose. Conclusions This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk., Author(s): Mattias Johansson 1,*, Robert Carreras-Torres 1, Ghislaine Scelo 1, Mark P. Purdue 2, Daniela Mariosa 1, David C. Muller 3, Nicolas J. Timpson 4, Philip C. Haycock 4, Kevin [...]
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- 2019
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34. Dietary intake of B vitamins and methionine and prostate cancer incidence and mortality
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Bassett, Julie K., Severi, Gianluca, Hodge, Allison M., Baglietto, Laura, Hopper, John L., English, Dallas R., and Giles, Graham G.
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- 2012
35. Circulating bilirubin levels and risk of colorectal cancer: serological and Mendelian randomization analyses
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Khoei, Nazlisadat Seyed, Jenab, Mazda, Murphy, Neil, Banbury, Barbara L., Carreras Torres, Robert, Viallon, Vivian, Kühn, Tilman, Bueno de Mesquita, H. Bas, Aleksandrova, Krasimira, Cross, Amanda J., Weiderpass, Elisabete, Stepien, Magdalena, Bulmer, Andrew, Tjønneland, Anne, Boutron-Ruault, Marie-Christine, Severi, Gianluca, Carbonnel, Franck, Katzke, Verena, Boeing, Heiner, Bergmann, Manuela M., Trichopoulou, Antonia, Karakatsani, Anna, Martimianaki, Georgia, Palli, Domenico, Tagliabue, Giovanna, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Skeie, Guri, Merino, Susana, Bonet Bonet, Catalina, Rodríguez Barranco, Miguel, Gil, Leire, Chirlaque, María Dolores, Ardanaz, Eva, Myte, Robin, Hultdin, Johan, Pérez Cornago, Aurora, Aune, Dagfinn, Tsilidis, Konstantinos K., Albanes, Demetrius, Baron, John A., Berndt, Sonja I., Bézieau, Stéphane, Brenner, Hermann, Campbell, Peter T., Casey, Graham, Chan, Andrew T., Chang Claude, Jenny, Chanock, Stephen J., Cotterchio, Michelle, Gallinger, Steven, Gruber, Stephen B., Haile, Robert W., Hampe, Jochen, Hoffmeister, Michael, Hopper, John L., Hsu, Li, Huyghe, Jeroen R., Jenkins, Mark A., Joshi, Amit D., Kampman, Ellen, Larsson, Susanna C., Marchand, Loïc Le, Li, Christopher I., Li, Li, Lindblom, Annika, Lindor, Noralane M., Martín Sánchez, Vicente, Moreno Aguado, Víctor, Newcomb, Polly A., Offit, Kenneth, Ogino, Shuji, Parfrey, Patrick S., Pharoah, Paul D. P., Rennert, Gad, Sakoda, Lori C., Schafmayer, Clemens, Schmit, Stephanie L., Schoen, Robert E., Slattery, Martha L., Thibodeau, Stephen N., Ulrich, Cornelia M., van Duijnhoven, Franzel J. B., Weigl, Korbinian, Weinstein, Stephanie J., White, Emily, Wolk, Alicja, Woods, Michael O., Wu, Anna H., Zhang, Xuehong, Ferrari, Pietro, Anton, Gabriele, Peters, Annette, Peters, Ulrike, Gunter, Marc J., Wagner, Karl-Heinz, Freisling, Heinz, Apollo - University of Cambridge Repository, and Pharoah, Paul [0000-0001-8494-732X]
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Adult ,Male ,Nutrition and Disease ,Mendelian randomization analysis ,lcsh:Medicine ,Polymorphism, Single Nucleotide ,Antioxidants ,Càncer colorectal ,Risk Factors ,Voeding en Ziekte ,Humans ,Prospective Studies ,VLAG ,Cancer ,Aged ,lcsh:R ,Bilirubin ,Middle Aged ,Colorectal cancer ,Europe ,Case-Control Studies ,Anti-oxidants ,Female ,Colorectal Neoplasms ,Research Article - Abstract
Background: Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex. Methods: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5 × 10−8) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study. Results: The associations between circulating UCB levels and CRC risk differed by sex (Pheterogeneity = 0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04–1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76–0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02–1.12); P = 0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96–1.06); P = 0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, were suggestive of an inverse association with CRC in men, but not in women. These differences by sex did not reach formal statistical significance (Pheterogeneity ≥ 0.2). Conclusions: Additional insight into the relationship between circulating bilirubin and CRC is needed in order to conclude on a potential causal role of bilirubin in CRC development.
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- 2020
36. Anthropometry and the Risk of Lung Cancer in EPIC
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Dewi, Nikmah Utami, Boshuizen, Hendriek C, Johansson, Mattias, Vineis, Paolo, Kampman, Ellen, Steffen, Annika, Tjønneland, Anne, Halkjær, Jytte, Overvad, Kim, Severi, Gianluca, Fagherazzi, Guy, Boutron-Ruault, Marie-Christine, Kaaks, Rudolf, Li, Kuanrong, Boeing, Heiner, Trichopoulou, Antonia, Bamia, Christina, Klinaki, Eleni, Tumino, Rosario, Palli, Domenico, Mattiello, Amalia, Tagliabue, Giovanna, Peeters, Petra H, Vermeulen, Roel, Weiderpass, Elisabete, Torhild Gram, Inger, Huerta, José María, Agudo, Antonio, Sánchez, María-José, Ardanaz, Eva, Dorronsoro, Miren, Quirós, José Ramón, Sonestedt, Emily, Johansson, Mikael, Grankvist, Kjell, Key, Tim, Khaw, Kay-Tee, Wareham, Nick, Cross, Amanda J, Norat, Teresa, Riboli, Elio, Fanidi, Anouar, Muller, David, Bueno-de-Mesquita, H Bas, LS IRAS EEPI GRA (Gezh.risico-analyse), dIRAS RA-I&I RA, dIRAS RA-2, LS IRAS EEPI GRA (Gezh.risico-analyse), dIRAS RA-I&I RA, dIRAS RA-2, and Imperial College Trust
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Male ,obesity ,Lung Neoplasms ,Nutrition and Disease ,Epidemiology ,Comorbidity ,waist to hip ratio ,ORIGINAL CONTRIBUTIONS ,Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14] ,0302 clinical medicine ,Waist–hip ratio ,Voeding en Ziekte ,Multicenter Studies as Topic ,Medicine ,Prospective Studies ,030212 general & internal medicine ,POPULATION ,Public, Environmental & Occupational Health ,Human Nutrition & Health ,Waist-to-height ratio ,Anthropometry ,Hazard ratio ,Humane Voeding & Gezondheid ,Confounding Factors, Epidemiologic ,11 Medical And Health Sciences ,Middle Aged ,waist circumference ,Europe ,LEANNESS ,030220 oncology & carcinogenesis ,Female ,Life Sciences & Biomedicine ,Adult ,medicine.medical_specialty ,Waist ,body mass index ,waist-to-height ratio ,Risk Assessment ,smoking ,03 medical and health sciences ,Journal Article ,Humans ,COHORT ,Lung cancer ,waist-to-heigh ratio ,METAANALYSIS ,01 Mathematical Sciences ,Aged ,Proportional Hazards Models ,VLAG ,MODEL ANALYSIS ,Science & Technology ,Waist-Hip Ratio ,business.industry ,Proportional hazards model ,CURRENT SMOKERS ,Cancer ,FAT DISTRIBUTION ,medicine.disease ,Diet ,Surgery ,BODY-MASS INDEX ,lung cancer ,business ,Body mass index ,Demography - Abstract
The associations of body mass index (BMI) and other anthropometric measurements with lung cancer were examined in 348,108 participants in the European Investigation Into Cancer and Nutrition (EPIC) between 1992 and 2010. The study population included 2,400 case patients with incident lung cancer, and the average length of follow-up was 11 years. Hazard ratios were calculated using Cox proportional hazard models in which we modeled smoking variables with cubic splines. Overall, there was a significant inverse association between BMI (weight (kg)/height (m)(2)) and the risk of lung cancer after adjustment for smoking and other confounders (for BMI of 30.0-34.9 versus 18.5-25.0, hazard ratio = 0.72, 95% confidence interval: 0.62, 0.84). The strength of the association declined with increasing follow-up time. Conversely, after adjustment for BMI, waist circumference and waist-to-height ratio were significantly positively associated with lung cancer risk (for the highest category of waist circumference vs. the lowest, hazard ratio = 1.25, 95% confidence interval: 1.05, 1.50). Given the decline of the inverse association between BMI and lung cancer over time, the association is likely at least partly due to weight loss resulting from preclinical lung cancer that was present at baseline. Residual confounding by smoking could also have influenced our findings.
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- 2016
37. Investigating the genetic relationship between Alzheimer’s disease and cancer using GWAS summary statistics
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Feng, Yen Chen Anne, Cho, Kelly, Lindstrom, Sara, Kraft, Peter, Cormack, Jean, Blalock, Kendra, Campbell, Peter T., Casey, Graham, Conti, David V., Edlund, Christopher K., Figueiredo, Jane, James Gauderman, W., Gong, Jian, Green, Roger C., Gruber, Stephen B., Harju, John F., Harrison, Tabitha A., Jacobs, Eric J, Jenkins, Mark A., Jiao, Shuo, Li, Li, Lin, Yi, Manion, Frank J., Moreno, Victor, Mukherjee, Bhramar, Peters, Ulrike, Raskin, Leon, Schumacher, Fredrick R., Seminara, Daniela, Severi, Gianluca, Stenzel, Stephanie L., Thomas, Duncan C., Hopper, John L., Southey, Melissa C., Makalic, Enes, Schmidt, Daniel F., Fletcher, Olivia, Peto, Julian, Gibson, Lorna, Dos-Santos-Silva, Isabel, Hunter, David J., Lindström, Sara, Ahsan, Habib, Whittemore, Alice S., Waisfisz, Quinten, Meijers-Heijboer, Hanne, Adank, Muriel A., van der Luijt, Rob B., Uitterlinden, Andre G, IGAP Consortium, Colorectal Transdisciplinary Study (CORECT), Discovery, Biology, and Risk of Inherited Variants in Breast Cancer (DRIVE), CCA - Cancer biology and immunology, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, and Amsterdam Reproduction & Development (AR&D)
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0301 basic medicine ,Male ,Genome-wide association study ,Single-nucleotide polymorphism ,Disease ,Biology ,Genetic correlation ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,Breast cancer ,SDG 3 - Good Health and Well-being ,Alzheimer Disease ,Neoplasms ,Genetics ,medicine ,Humans ,Genetics(clinical) ,1000 Genomes Project ,Genetics (clinical) ,Cancer ,medicine.disease ,030104 developmental biology ,Adenocarcinoma ,Female ,Genome-Wide Association Study - Abstract
Growing evidence from both epidemiology and basic science suggest an inverse association between Alzheimer’s disease (AD) and cancer. We examined the genetic relationship between AD and various cancer types using GWAS summary statistics from the IGAP and GAME-ON consortia. Sample size ranged from 9931 to 54,162; SNPs were imputed to the 1000 Genomes European panel. Our results based on cross-trait LD Score regression showed a significant positive genetic correlation between AD and five cancers combined (colon, breast, prostate, ovarian, lung; r g = 0.17, P = 0.04), and specifically with breast cancer (ER-negative and overall; r g = 0.21 and 0.18, P = 0.035 and 0.034) and lung cancer (adenocarcinoma, squamous cell carcinoma and overall; r g = 0.31, 0.38 and 0.30, P = 0.029, 0.016, and 0.006). Estimating the genetic correlation in specific functional categories revealed mixed positive and negative signals, notably stronger at annotations associated with increased enhancer activity. This suggests a role of gene expression regulators in the shared genetic etiology between AD and cancer, and that some shared variants modulate disease risk concordantly while others have effects in opposite directions. Due to power issues, we did not detect cross-phenotype associations at individual SNPs. This genetic overlap is not likely driven by a handful of major loci. Our study is the first to examine the co-heritability of AD and cancer leveraging large-scale GWAS results. The functional categories highlighted in this study need further investigation to illustrate the details of the genetic sharing and to bridge between different levels of associations.
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- 2017
38. Blood pressure and risk of cancer in the European Prospective Investigation into Cancer and Nutrition.
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Christakoudi, Sofia, Kakourou, Artemisia, Markozannes, Georgios, Tzoulaki, Ioanna, Weiderpass, Elisabete, Brennan, Paul, Gunter, Marc, Dahm, Christina C., Overvad, Kim, Olsen, Anja, Tjønneland, Anne, Boutron‐Ruault, Marie‐Christine, Madika, Anne‐Laure, Severi, Gianluca, Katzke, Verena, Kühn, Tilman, Bergmann, Manuela M., Boeing, Heiner, Karakatsani, Anna, and Martimianaki, Georgia
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BLOOD pressure ,HEAD & neck cancer ,HEMATOLOGIC malignancies ,PROPORTIONAL hazards models ,RENAL cell carcinoma - Abstract
Several studies have reported associations of hypertension with cancer, but not all results were conclusive. We examined the association of systolic (SBP) and diastolic (DBP) blood pressure with the development of incident cancer at all anatomical sites in the European Prospective Investigation into Cancer and Nutrition (EPIC). Hazard ratios (HRs) (95% confidence intervals) were estimated using multivariable Cox proportional hazards models, stratified by EPIC‐participating center and age at recruitment, and adjusted for sex, education, smoking, body mass index, physical activity, diabetes and dietary (in women also reproductive) factors. The study included 307,318 men and women, with an average follow‐up of 13.7 (standard deviation 4.4) years and 39,298 incident cancers. We confirmed the expected positive association with renal cell carcinoma: HR = 1.12 (1.08–1.17) per 10 mm Hg higher SBP and HR = 1.23 (1.14–1.32) for DBP. We additionally found positive associations for esophageal squamous cell carcinoma (SCC): HR = 1.16 (1.07–1.26) (SBP), HR = 1.31 (1.13–1.51) (DBP), weaker for head and neck cancers: HR = 1.08 (1.04–1.12) (SBP), HR = 1.09 (1.01–1.17) (DBP) and, similarly, for skin SCC, colon cancer, postmenopausal breast cancer and uterine adenocarcinoma (AC), but not for esophageal AC, lung SCC, lung AC or uterine endometroid cancer. We observed weak inverse associations of SBP with cervical SCC: HR = 0.91 (0.82–1.00) and lymphomas: HR = 0.97 (0.93–1.00). There were no consistent associations with cancers in other locations. Our results are largely compatible with published studies and support weak associations of blood pressure with cancers in specific locations and morphologies. What's new? Is there a link between high blood pressure and cancer? In this large, prospective study, the authors found that hypertension is indeed associated with a moderate increase in risk for several cancers, including renal, esophageal (only squamous cell carcinoma), head and neck, skin, colon, post‐menopausal breast cancer, and uterine cancer (only adenocarcinoma). These results may potentially enhance screening and risk assessment. Further research may also identify shared mechanisms for both hypertension and cancer, such as inflammation, lipid peroxidation, etc. [ABSTRACT FROM AUTHOR]
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- 2020
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39. A meta-analysis of individual participant data reveals an association between circulating levels of IGF-I and prostate cancer risk
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Travis, Ruth, Appleby, Paul, Martin, Richard, Holly, Jeff M.P., Albanes, Demetrius, Black, Amanda, Bueno-De-Mesquita, H. Bas, Chan, June, Chen, Chu, Chirlaque, María-Dolores, Cook, Michael, Deschasaux, Mélanie, Donovan, Jenny, Ferrucci, Luigi, Galan, Pilar, Giles, Graham, Giovannucci, Edward, Gunter, Marc, Habel, Laurel, Hamdy, Freddie, Helzlsouer, Kathy, Hercberg, Serge, Hoover, Robert, Janssen, Joseph A.M.J.L., Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loïc, Metter, E. Jeffrey, Mikami, Kazuya, Morris, Joan, Neal, David, Neuhouser, Marian, Ozasa, Kotaro, Palli, Domenico, Platz, Elizabeth, Pollak, Michael, Price, Alison, Roobol, Monique, Schaefer, Catherine, Schenk, Jeannette, Severi, Gianluca, Stampfer, Meir, Stattin, Pär, Tamakoshi, Akiko, Tangen, Catherine, Touvier, Mathilde, Wald, Nicholas, Weiss, Noel, Ziegler, Regina, Key, Timothy, Allen, Naomi, Nuffield Department of Population Health [Oxford], University of Oxford [Oxford], School of Social and Community Medicine [Bristol], University of Bristol [Bristol], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), National Institute for Public Health and the Environment [Bilthoven] (RIVM), University of California [San Francisco] (UCSF), University of California, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Consorcio de Investigación Biomédica en Red especializado en Epidemiología y Salud Pública (CIBERESP), Los Centros de Investigación Biomédica en Red (CIBER), Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Institute on Aging [Bethesda, USA] (NIA), University of Melbourne, Harvard School of Public Health, School of Public Health - Department of Epidemiology and Biostatistics, Imperial College London, Kaiser Permanente, Nuffield (Nuffield), Mercy Medical Center, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University of Occupational and Environmental Health [Kitakyushu] (UEOH), University of Hawai‘i [Mānoa] (UHM), Kyoto Prefectural University of Medicine [Kyoto, Japon], Queen Mary University of London (QMUL), University of Cambridge [UK] (CAM), Radiation Effects Research Foundation, Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Cancer Prevention Research Unit, Department of Oncology, McGill University = Université McGill [Montréal, Canada]-Jewish General Hospital, University of Washington [Seattle], Cancer Epidemiology Centre, Cancer Council Victoria, Human Genetics Foundation (HuGeF), Department of Surgical and Perioperative Sciences, Urology and Andrology, Umeå University, Hokkaido University Hospital [Sapporo], University of Oxford, University of California [San Francisco] (UC San Francisco), University of California (UC), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), and Deschasaux-Tanguy, Mélanie
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Urologic Diseases ,Male ,Aging ,Oncology and Carcinogenesis ,Article ,growth-factor-i ,serum-insulin ,Risk Factors ,prevention trial ,Humans ,Oncology & Carcinogenesis ,Insulin-Like Growth Factor I ,factor axis ,igfbp-3 ,Cancer ,Aged ,Prostate Cancer ,hyperplasia ,Prostatic Neoplasms ,Middle Aged ,susceptibility loci ,[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,factor-binding protein-2 ,Centre for Surgical Research ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,factor (igf)-i ,diet ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition - Abstract
The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. Aftermutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development.
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- 2016
40. Carotenoids, retinol, tocopherols, and prostate cancer risk: pooled analysis of 15 studies
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Key, Timothy J, Appleby, Paul N, Travis, Ruth C, Albanes, Demetrius, Alberg, Anthony J, Barricarte, Aurelio, Black, Amanda, Boeing, Heiner, Bueno-de-Mesquita, H Bas, Chan, June M, Chen, Chu, Cook, Michael B, Donovan, Jenny L, Galan, Pilar, Gilbert, Rebecca, Giles, Graham G, Giovannucci, Edward, Goodman, Gary E, Goodman, Phyllis J, Gunter, Marc J, Hamdy, Freddie C, Heliövaara, Markku, Helzlsouer, Kathy J, Henderson, Brian E, Hercberg, Serge, Hoffman-Bolton, Judy, Hoover, Robert N, Johansson, Mattias, Khaw, Kay-Tee, King, Irena B, Knekt, Paul, Kolonel, Laurence N, Le Marchand, Loic, Männistö, Satu, Martin, Richard M, Meyer, Haakon E, Mondul, Alison M, Moy, Kristin A, Neal, David E, Neuhouser, Marian L, Palli, Domenico, Platz, Elizabeth A, Pouchieu, Camille, Rissanen, Harri, Schenk, Jeannette M, Severi, Gianluca, Stampfer, Meir J, Tjønneland, Anne, Touvier, Mathilde, Trichopoulou, Antonia, Weinstein, Stephanie J, Ziegler, Regina G, Zhou, Cindy Ke, Allen, Naomi E, and Endogenous Hormones Nutritional Biomarkers Prostate Cancer Collaborative Group
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Adult ,Male ,Urologic Diseases ,Aging ,alpha-Tocopherol ,vitamin E ,Medical and Health Sciences ,vitamin A ,Cohort Studies ,Lycopene ,Engineering ,Meta-Analysis as Topic ,nested case-control study ,Risk Factors ,Clinical Research ,Humans ,Prospective Studies ,Neoplasm Staging ,Cancer ,Nutrition ,Endogenous Hormones Nutritional Biomarkers Prostate Cancer Collaborative Group ,Nutrition & Dietetics ,Prostate Cancer ,Prevention ,Prostate ,carotenoids ,Prostatic Neoplasms ,biomarkers ,Middle Aged ,Observational Studies as Topic ,Cross-Sectional Studies ,Case-Control Studies ,Neoplasm Grading ,pooled analysis ,tocopherols ,retinol - Abstract
BackgroundIndividual studies have suggested that circulating carotenoids, retinol, or tocopherols may be associated with prostate cancer risk, but the studies have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease.ObjectiveThe objective of this study was to conduct a pooled analysis of the associations of the concentrations of 7 carotenoids, retinol, α-tocopherol, and γ-tocopherol with risk of prostate cancer and to describe whether any associations differ by stage or grade of the disease or other factors.DesignPrincipal investigators of prospective studies provided individual participant data for prostate cancer cases and controls. Risk by study-specific fifths of each biomarker was estimated by using multivariable-adjusted conditional logistic regression in matched case-control sets.ResultsData were available for up to 11,239 cases (including 1654 advanced stage and 1741 aggressive) and 18,541 controls from 15 studies. Lycopene was not associated with overall risk of prostate cancer, but there was statistically significant heterogeneity by stage of disease, and the OR for aggressive disease for the highest compared with the lowest fifth of lycopene was 0.65 (95% CI: 0.46, 0.91; P-trend = 0.032). No other carotenoid was significantly associated with overall risk of prostate cancer or with risk of advanced-stage or aggressive disease. For retinol, the OR for the highest compared with the lowest fifth was 1.13 (95% CI: 1.04, 1.22; P-trend = 0.015). For α-tocopherol, the OR for the highest compared with the lowest fifth was 0.86 (95% CI: 0.78, 0.94; P-trend < 0.001), with significant heterogeneity by stage of disease; the OR for aggressive prostate cancer was 0.74 (95% CI: 0.59, 0.92; P-trend = 0.001). γ-Tocopherol was not associated with risk.ConclusionsOverall prostate cancer risk was positively associated with retinol and inversely associated with α-tocopherol, and risk of aggressive prostate cancer was inversely associated with lycopene and α-tocopherol. Whether these associations reflect causal relations is unclear.
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- 2015
41. Corrigendum: genome-wide association study of colorectal cancer identifies six new susceptibility loci
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Schumacher, Fredrick R, Schmit, Stephanie L, Jiao, Shuo, Edlund, Christopher K, Wang, Hansong, Zhang, Ben, Hsu, Li, Huang, Shu-Chen, Fischer, Christopher P, Harju, John F, Idos, Gregory E, Lejbkowicz, Flavio, Manion, Frank J, McDonnell, Kevin, McNeil, Caroline E, Melas, Marilena, Rennert, Hedy S, Shi, Wei, Thomas, Duncan C, Van Den Berg, David J, Hutter, Carolyn M, Aragaki, Aaron K, Butterbach, Katja, Caan, Bette J, Carlson, Christopher S, Chanock, Stephen J, Curtis, Keith R, Fuchs, Charles S, Gala, Manish, Giovannucci, Edward L, Gogarten, Stephanie M, Hayes, Richard B, Henderson, Brian, Hunter, David J, Jackson, Rebecca D, Kolonel, Laurence N, Kooperberg, Charles, Küry, Sébastien, LaCroix, Andrea, Laurie, Cathy C, Laurie, Cecelia A, Lemire, Mathieu, Levine, David, Ma, Jing, Makar, Karen W, Qu, Conghui, Taverna, Darin, Ulrich, Cornelia M, Wu, Kana, Kono, Suminori, West, Dee W, Berndt, Sonja I, Bezieau, Stephane, Brenner, Hermann, Campbell, Peter T, Chan, Andrew T, Chang-Claude, Jenny, Coetzee, Gerhard A, Conti, David V, Duggan, David, Figueiredo, Jane C, Fortini, Barbara K, Gallinger, Steven J, Gauderman, W James, Giles, Graham, Green, Roger, Haile, Robert, Harrison, Tabitha A, Hoffmeister, Michael, Hopper, John L, Hudson, Thomas J, Jacobs, Eric, Iwasaki, Motoki, Jee, Sun Ha, Jenkins, Mark, Jia, Wei-Hua, Joshi, Amit, Li, Li, Lindor, Noralene M, Matsuo, Keitaro, Moreno, Victor, Mukherjee, Bhramar, Newcomb, Polly A, Potter, John D, Raskin, Leon, Rennert, Gad, Rosse, Stephanie, Severi, Gianluca, Schoen, Robert E, Seminara, Daniela, Shu, Xiao-Ou, Slattery, Martha L, Tsugane, Shoichiro, White, Emily, Xiang, Yong-Bing, Zanke, Brent W, Zheng, Wei, Le Marchand, Loic, Casey, Graham, and Gruber, Stephen B
- Subjects
MD Multidisciplinary ,Digestive Diseases ,Cancer ,Colo-Rectal Cancer - Published
- 2015
42. Computational tools to detect signatures of mutational processes in DNA from tumours: A review and empirical comparison of performance.
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Omichessan, Hanane, Severi, Gianluca, and Perduca, Vittorio
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CIRCULATING tumor DNA , *TUMORS , *CANCER , *SOMATIC mutation , *DNA , *MUTAGENS - Abstract
Mutational signatures refer to patterns in the occurrence of somatic mutations that might be uniquely ascribed to particular mutational process. Tumour mutation catalogues can reveal mutational signatures but are often consistent with the mutation spectra produced by a variety of mutagens. To date, after the analysis of tens of thousands of exomes and genomes from about 40 different cancer types, tens of mutational signatures characterized by a unique probability profile across the 96 trinucleotide-based mutation types have been identified, validated and catalogued. At the same time, several concurrent methods have been developed for either the quantification of the contribution of catalogued signatures in a given cancer sequence or the identification of new signatures from a sample of cancer sequences. A review of existing computational tools has been recently published to guide researchers and practitioners through their mutational signature analyses, but other tools have been introduced since its publication and, a systematic evaluation and comparison of the performance of such tools is still lacking. In order to fill this gap, we have carried out an empirical evaluation of the main packages available to date, using both real and simulated data. Among other results, our empirical study shows that the identification of signatures is more difficult for cancers characterized by multiple signatures each having a small contribution. This work suggests that detection methods based on probabilistic models, especially EMu and bayesNMF, have in general better performance than NMF-based methods. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
43. Association of DNA Methylation-Based Biological Age With Health Risk Factors and Overall and Cause-Specific Mortality.
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Dugué, Pierre-Antoine, Bassett, Julie K., JiHoon E. Joo, Baglietto, Laura, Chol-Hee Jung, Ee Ming Wong, Fiorito, Giovanni, Schmidt, Daniel, Makalic, Enes, Shuai Li, Moreno-Betancur, Margarita, Buchanan, Daniel D., Vineis, Paolo, English, Dallas R., Hopper, John L., Severi, Gianluca, Southey, Melissa C., Giles, Graham G., and Milne, Roger L.
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AGE distribution ,AGING ,CAUSES of death ,DIABETES ,ETHNIC groups ,MEAT ,OBESITY ,RISK assessment ,SEX distribution ,SMOKING ,EDUCATIONAL attainment ,MICROARRAY technology ,DNA methylation ,HEALTH & social status ,EPIGENOMICS - Abstract
Measures of biological age based on blood DNA methylation, referred to as age acceleration (AA), have been developed. We examined whether AA was associated with health risk factors and overall and cause-specific mortality. At baseline (1990-1994), blood samples were drawn from 2,818 participants in the Melbourne Collaborative Cohort Study (Melbourne, Victoria, Australia). DNA methylation was determined using the Infinium Human Methylation 450 BeadChip array (Illumina Inc., San Diego, California). Mixed-effects models were used to examine the association of AA with health risk factors. Cox models were used to assess the association of AA with mortality. A total of 831 deaths were observed during a median 10.7 years of follow-up. Associations of AA were observed with male sex, Greek nationality (country of birth), smoking, obesity, diabetes, lower education, and meat intake. AA measures were associated with increased mortality, and this was only partly accounted for by known determinants of health (hazard ratios were attenuated by 20%-40%). Weak evidence of heterogeneity in the association was observed by sex (P = 0.06) and cause of death (P = 0.07) but not by other factors. DNA-methylation-based AA measures are associated with several major health risk factors, but these do not fully explain the association between AA and mortality. Future research should investigate what genetic and environmental factors determine AA. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
44. Correspondence.
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Temple, Norman J., Elwood, J. Mark, Gallagher, Richard P., Autier, Phillippe, Dore, Jean-Francois, Severi, Gianluca, Durie, Brian G.M., Urnovitz, Howard B., Butel, Janet S., Lednicky, John A., Love, Richard R., Olsen, Mark R., and Havighurst, Thomas C.
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CANCER ,CAROTENES ,SV40 (Virus) ,SUNSCREENS (Cosmetics) ,PHYSIOLOGY - Abstract
Outlines comments and responses on studies about cancer. Negative results of beta-carotene supplements on cancer; Risk on the use of sunscreen and the incidence of melanocytic lesions; Involvement of the simian virus 40 in the pathogenesis of human malignancies.
- Published
- 1999
45. Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases: a multinational cohort study
- Author
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Freisling, Heinz, Viallon, Vivian, Lennon, Hannah, Bagnardi, Vincenzo, Ricci, Cristian, Butterworth, Adam S., Sweeting, Michael, Muller, David, Romieu, Isabelle, Bazelle, Pauline, Kvaskoff, Marina, Arveux, Patrick, Severi, Gianluca, Bamia, Christina, Kühn, Tilman, Kaaks, Rudolf, Bergmann, Manuela, Boeing, Heiner, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Dahm, Christina C., Menéndez, Virginia, Agudo, Antonio, Sánchez, Maria-Jose, Amiano, Pilar, Santiuste, Carmen, Gurrea, Aurelio Barricarte, Tong, Tammy Y. N., Schmidt, Julie A., Tzoulaki, Ioanna, Tsilidis, Konstantinos K., Ward, Heather, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Picavet, H. Susan J., Bakker, Marije, Monninkhof, Evelyn, Nilsson, Peter, Manjer, Jonas, Rolandsson, Olov, Thysell, Elin, Weiderpass, Elisabete, Jenab, Mazda, Riboli, Elio, Vineis, Paolo, Danesh, John, Wareham, Nick J., Gunter, Marc J., and Ferrari, Pietro
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2. Zero hunger ,Prevention ,Cancer and cardiometabolic multimorbidity ,Diabetes ,Healthy lifestyle ,Obesity ,Cardiovascular disease ,3. Good health ,Research Article ,Cancer - Abstract
Background: Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases. Methods: In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs. Results: During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and women with healthy lifestyles. Conclusion: Pre-diagnostic healthy lifestyle behaviours were strongly inversely associated with the risk of cancer and cardiometabolic diseases, and with the prognosis of these diseases by reducing risk of multimorbidity.
46. Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases: a multinational cohort study
- Author
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Freisling, Heinz, Viallon, Vivian, Lennon, Hannah, Bagnardi, Vincenzo, Ricci, Cristian, Butterworth, Adam S., Sweeting, Michael, Muller, David, Romieu, Isabelle, Bazelle, Pauline, Kvaskoff, Marina, Arveux, Patrick, Severi, Gianluca, Bamia, Christina, Kühn, Tilman, Kaaks, Rudolf, Bergmann, Manuela, Boeing, Heiner, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Dahm, Christina C., Menéndez, Virginia, Agudo, Antonio, Sánchez, Maria-Jose, Amiano, Pilar, Santiuste, Carmen, Gurrea, Aurelio Barricarte, Tong, Tammy Y. N., Schmidt, Julie A., Tzoulaki, Ioanna, Tsilidis, Konstantinos K., Ward, Heather, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Picavet, H. Susan J., Bakker, Marije, Monninkhof, Evelyn, Nilsson, Peter, Manjer, Jonas, Rolandsson, Olov, Thysell, Elin, Weiderpass, Elisabete, Jenab, Mazda, Riboli, Elio, Vineis, Paolo, Danesh, John, Wareham, Nick J., Gunter, Marc J., and Ferrari, Pietro
- Subjects
2. Zero hunger ,Prevention ,Cancer and cardiometabolic multimorbidity ,Diabetes ,Healthy lifestyle ,Obesity ,Cardiovascular disease ,3. Good health ,Research Article ,Cancer - Abstract
Background: Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases. Methods: In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs. Results: During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and women with healthy lifestyles. Conclusion: Pre-diagnostic healthy lifestyle behaviours were strongly inversely associated with the risk of cancer and cardiometabolic diseases, and with the prognosis of these diseases by reducing risk of multimorbidity.
47. Detectable clonal mosaicism and its relationship to aging and cancer
- Author
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Jacobs, Kevin B., Yeager, Meredith, Zhou, Weiyin, Wacholder, Sholom, Wang, Zhaoming, Rodriguez-Santiago, Benjamin, Hutchinson, Amy, Deng, Xiang, Liu, Chenwei, Horner, Marie-Josephe, Cullen, Michael, Liao, Linda, Schwartz, Ann G., McNeill, Lorna H., Schwenn, Molly, Figueroa, Jonine D., Henderson, Brian E., Shu, Xiao-Ou, Zeleniuch-Jacquotte, Anne, Wiencke, John K., Gonzalez, Juan R., Gallinger, Steven, Fan, Jin-Hu, Thomas, Gilles, Wrensch, Margaret, Savage, Sharon A., Silverman, Debra T., Amos, Christopher I., Tang, Ze-Zhong, Sierrasesúmaga, Luis, Consonni, Dario, Albanes, Demetrius, Trichopoulos, Dimitrios, Olson, Sara H., Chow, Wong-Ho, Krogh, Vittorio, Beane Freeman, Laura, Kratz, Christian P., Holly, Elizabeth A., Blot, William J., Hallmans, Göran, Peters, Ulrike, Duell, Eric J., Brinton, Louise A., Yu, Herbert, Hoover, Robert N., Caporaso, Neil E ., Bertazzi, Pier Alberto, Chanock, Stephen J., Erickson, Ralph L., Elena, Joanne W., Visvanathan, Kala, Tobias, Geoffrey S., Rothman, Nathaniel, Gross, Myron D., Hassan, Manal, Chang, Kenneth, Cotterchio, Michelle, Johnson, Alison, Moore, Lee E., Rajaraman, Preetha, Purdue, Mark, Klein, Alison P., Wheeler, William, Wentzensen, Nicolas, Tjønneland, Anne, Arslan, Alan A., Petersen, Gloria, Chatterjee, Nilanjan, Canzian, Federico, Goggins, Michael, Landi, Maria Teresa, Kurtz, Robert C., Graubard, Barry I., Kovaks, Joseph, Marenne, Gaelle, Dean, Michael C., Giovannucci, Edward L., Wunder, Jay S., Andrulis, Irene L., Butler, Mary A., Jenab, Mazda, Bueno de Mesquita, H. Bas, Marchand, Loic Le, Carreon, Tania, Goldin, Lynn, Virtamo, Jarmo, Ruder, Avima M., Peplonska, Beata, Burdett, Laurie, Sampson, Joshua, Gorlick, Richard G., Fuchs, Charles S., Chung, Charles C., Barkauskas, Donald A., Taylor, Philip R., Haiman, Christopher A., Hunter, David J., Gapstur, Susan M., Giles, Graham G., White, Emily, Mendelsohn, Julie B., Zheng, Wei, Lissowska, Jolanta, Amundadottir, Laufey, Andersson, Ulrika, Davis, Faith G., Freedman, Neal D., Boutron-Ruault, Marie-Christine, LaCroix, Andrea, Rabe, Kari G., Hankinson, Susan E., Bracci, Paige M., McKean-Cowdin, Roberta, Weinstein, Stephanie J., Mandelson, Margaret T., Gao, Yu-Tang, Kolonel, Laurence N., Harris, Curtis C., Teras, Lauren T., Fraumeni Jr., Joseph F., Greene, Mark H., Sesso, Howard D., Mirabello, Lisa, Schwartz, Kendra L., Risch, Harvey A., Abnet, Christian C., Prokunina-Olsson, Ludmila, Garcia Closas, Montserrat, Michaud, Dominique S., Stevens, Victoria L., Signorello, Lisa B., Tucker, Margaret, Ding, Ti, Aldrich, Melinda C., Stram, Daniel, Kraft, Peter, Pérez Jurado, Luis A., Berg, Christine D., Hoffman Bolton, Judith A., Koh, Woon-Puay, Buring, Julie E., Ziegler, Regina G., Bock, Cathryn H., McWilliams, Robert R., Feychting, Maria, Goldstein, Alisa M., Hartge, Patricia, Johansen, Christoffer, Hu, Nan, Patiño García, Ana, Rotunno, Melissa, Gillanders, Elizabeth M., Rybicki, Benjamin A., Spitz, Margaret R., Riboli, Elio, Gaziano, J. Michael, Epstein, Caroline G., Khaw, Kay-Tee, Inskip, Peter D., Melin, Beatrice S., Severi, Gianluca, McGlynn, Katherine A., Wolpin, Brian M., Henriksson, Roger, Stolzenberg-Solomon, Rachael Z., Qiao, You-Lin, Gaudet, Mia M., Wu, Xifeng, Berndt, Sonja I., Yu, Kai, Hsing, Ann W., Landgren, Annelie, Wolk, Alicja, Xiang, Yong-Bing, Ahlbom, Anders, Cook, Michael B., Black, Amanda, Baris, Dalsu, Yuan, Jian-Min, Li, Donghui, Malats, Núria, Jiao, Li, Kogevinas, Manolis, Kooperberg, Charles, Villa, Olaya, Real, Francisco X., Zanetti, Krista A., and Schumacher, Fredrick
- Subjects
Aging ,Envelliment ,Càncer ,Cancer - Abstract
In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of > 2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 x 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 x 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
48. Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases: a multinational cohort study
- Author
-
Freisling, Heinz, Viallon, Vivian, Lennon, Hannah, Bagnardi, Vincenzo, Ricci, Cristian, Butterworth, Adam S, Sweeting, Michael, Muller, David, Romieu, Isabelle, Bazelle, Pauline, Kvaskoff, Marina, Arveux, Patrick, Severi, Gianluca, Bamia, Christina, Kühn, Tilman, Kaaks, Rudolf, Bergmann, Manuela, Boeing, Heiner, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Dahm, Christina C, Menéndez, Virginia, Agudo, Antonio, Sánchez, Maria-Jose, Amiano, Pilar, Santiuste, Carmen, Gurrea, Aurelio Barricarte, Tong, Tammy Y N, Schmidt, Julie A, Tzoulaki, Ioanna, Tsilidis, Konstantinos K, Ward, Heather, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Picavet, H Susan J, Bakker, Marije, Monninkhof, Evelyn, Nilsson, Peter, Manjer, Jonas, Rolandsson, Olov, Thysell, Elin, Weiderpass, Elisabete, Jenab, Mazda, Riboli, Elio, Vineis, Paolo, Danesh, John, Wareham, Nick J, Gunter, Marc J, and Ferrari, Pietro
- Subjects
2. Zero hunger ,Prevention ,Diabetes ,Obesity ,Healthy Lifestyle ,Cardiovascular disease ,3. Good health ,Cancer ,Cancer And Cardiometabolic Multimorbidity - Abstract
BACKGROUND:Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases. METHODS:In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs. RESULTS:During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and women with healthy lifestyles. CONCLUSION:Pre-diagnostic healthy lifestyle behaviours were strongly inversely associated with the risk of cancer and cardiometabolic diseases, and with the prognosis of these diseases by reducing risk of multimorbidity.
49. Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases: a multinational cohort study
- Author
-
Freisling, Heinz, Viallon, Vivian, Lennon, Hannah, Bagnardi, Vincenzo, Ricci, Cristian, Butterworth, Adam S, Sweeting, Michael, Muller, David, Romieu, Isabelle, Bazelle, Pauline, Kvaskoff, Marina, Arveux, Patrick, Severi, Gianluca, Bamia, Christina, Kühn, Tilman, Kaaks, Rudolf, Bergmann, Manuela, Boeing, Heiner, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Dahm, Christina C, Menéndez, Virginia, Agudo, Antonio, Sánchez, Maria-Jose, Amiano, Pilar, Santiuste, Carmen, Gurrea, Aurelio Barricarte, Tong, Tammy YN, Schmidt, Julie A, Tzoulaki, Ioanna, Tsilidis, Konstantinos K, Ward, Heather, Palli, Domenico, Agnoli, Claudia, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Picavet, H Susan J, Bakker, Marije, Monninkhof, Evelyn, Nilsson, Peter, Manjer, Jonas, Rolandsson, Olov, Thysell, Elin, Weiderpass, Elisabete, Jenab, Mazda, Riboli, Elio, Vineis, Paolo, Danesh, John, Wareham, Nick J, Gunter, Marc J, and Ferrari, Pietro
- Subjects
Adult ,Male ,Alcohol Drinking ,Healthy lifestyle ,Body Mass Index ,Cohort Studies ,Risk Factors ,Neoplasms ,Cancer and cardiometabolic multimorbidity ,Humans ,Obesity ,Prospective Studies ,Life Style ,Cancer ,Proportional Hazards Models ,2. Zero hunger ,Prevention ,Incidence ,Diabetes ,Multimorbidity ,Middle Aged ,Cardiovascular disease ,3. Good health ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Female ,Risk Reduction Behavior - Abstract
BACKGROUND: Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases. METHODS: In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs. RESULTS: During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and women with healthy lifestyles. CONCLUSION: Pre-diagnostic healthy lifestyle behaviours were strongly inversely associated with the risk of cancer and cardiometabolic diseases, and with the prognosis of these diseases by reducing risk of multimorbidity.
50. Re: Prospective Studies of Dairy Product and Calcium Intakes and Prostate Cancer Risk: A Meta-AnaIysis.
- Author
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Severi, Gianluca, English, Dallas R., Hopper, John L., and Giles, Graham G.
- Subjects
- *
LETTERS to the editor , *CANCER - Abstract
A letter to the editor is presented in response to the article about prostate cancer.
- Published
- 2006
- Full Text
- View/download PDF
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