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1. Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types

Author

Sampson, Joshua N, Wheeler, William A, Yeager, Meredith, Panagiotou, Orestis, Wang, Zhaoming, Berndt, Sonja I, Lan, Qing, Abnet, Christian C, Amundadottir, Laufey T, Figueroa, Jonine D, Landi, Maria Teresa, Mirabello, Lisa, Savage, Sharon A, Taylor, Philip R, De Vivo, Immaculata, McGlynn, Katherine A, Purdue, Mark P, Rajaraman, Preetha, Adami, Hans-Olov, Ahlbom, Anders, Albanes, Demetrius, Amary, Maria Fernanda, An, She-Juan, Andersson, Ulrika, Andriole, Gerald, Andrulis, Irene L, Angelucci, Emanuele, Ansell, Stephen M, Arici, Cecilia, Armstrong, Bruce K, Arslan, Alan A, Austin, Melissa A, Baris, Dalsu, Barkauskas, Donald A, Bassig, Bryan A, Becker, Nikolaus, Benavente, Yolanda, Benhamou, Simone, Berg, Christine, Van Den Berg, David, Bernstein, Leslie, Bertrand, Kimberly A, Birmann, Brenda M, Black, Amanda, Boeing, Heiner, Boffetta, Paolo, Boutron-Ruault, Marie-Christine, Bracci, Paige M, Brinton, Louise, Brooks-Wilson, Angela R, Bueno-de-Mesquita, H Bas, Burdett, Laurie, Buring, Julie, Butler, Mary Ann, Cai, Qiuyin, Cancel-Tassin, Geraldine, Canzian, Federico, Carrato, Alfredo, Carreon, Tania, Carta, Angela, Chan, John KC, Chang, Ellen T, Chang, Gee-Chen, Chang, I-Shou, Chang, Jiang, Chang-Claude, Jenny, Chen, Chien-Jen, Chen, Chih-Yi, Chen, Chu, Chen, Chung-Hsing, Chen, Constance, Chen, Hongyan, Chen, Kexin, Chen, Kuan-Yu, Chen, Kun-Chieh, Chen, Ying, Chen, Ying-Hsiang, Chen, Yi-Song, Chen, Yuh-Min, Chien, Li-Hsin, Chirlaque, María-Dolores, Choi, Jin Eun, Choi, Yi Young, Chow, Wong-Ho, Chung, Charles C, Clavel, Jacqueline, Clavel-Chapelon, Françoise, Cocco, Pierluigi, Colt, Joanne S, Comperat, Eva, Conde, Lucia, Connors, Joseph M, Conti, David, Cortessis, Victoria K, Cotterchio, Michelle, Cozen, Wendy, Crouch, Simon, Crous-Bou, Marta, Cussenot, Olivier, and Davis, Faith G

Subjects
Tobacco, Clinical Research, Urologic Diseases, Lung, Genetics, Rare Diseases, Lung Cancer, Human Genome, Hematology, Cancer, Tobacco Smoke and Health, Prevention, Lymphoma, Adult, Aged, Asian People, Bone Neoplasms, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Kidney Neoplasms, Leukemia, Lymphocytic, Chronic, B-Cell, Lung Neoplasms, Lymphoma, Large B-Cell, Diffuse, Male, Middle Aged, Neoplasms, Osteosarcoma, Polymorphism, Single Nucleotide, Smoking, Testicular Neoplasms, Tissue Array Analysis, Urinary Bladder Neoplasms, White People, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

BackgroundStudies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.MethodsBetween 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers.ResultsGWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures.ConclusionOur results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.

Published
2015

2. Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types.

Author

Sampson, Joshua N, Wheeler, William A, Yeager, Meredith, Panagiotou, Orestis, Wang, Zhaoming, Berndt, Sonja I, Lan, Qing, Abnet, Christian C, Amundadottir, Laufey T, Figueroa, Jonine D, Landi, Maria Teresa, Mirabello, Lisa, Savage, Sharon A, Taylor, Philip R, De Vivo, Immaculata, McGlynn, Katherine A, Purdue, Mark P, Rajaraman, Preetha, Adami, Hans-Olov, Ahlbom, Anders, Albanes, Demetrius, Amary, Maria Fernanda, An, She-Juan, Andersson, Ulrika, Andriole, Gerald, Andrulis, Irene L, Angelucci, Emanuele, Ansell, Stephen M, Arici, Cecilia, Armstrong, Bruce K, Arslan, Alan A, Austin, Melissa A, Baris, Dalsu, Barkauskas, Donald A, Bassig, Bryan A, Becker, Nikolaus, Benavente, Yolanda, Benhamou, Simone, Berg, Christine, Van Den Berg, David, Bernstein, Leslie, Bertrand, Kimberly A, Birmann, Brenda M, Black, Amanda, Boeing, Heiner, Boffetta, Paolo, Boutron-Ruault, Marie-Christine, Bracci, Paige M, Brinton, Louise, Brooks-Wilson, Angela R, Bueno-de-Mesquita, H Bas, Burdett, Laurie, Buring, Julie, Butler, Mary Ann, Cai, Qiuyin, Cancel-Tassin, Geraldine, Canzian, Federico, Carrato, Alfredo, Carreon, Tania, Carta, Angela, Chan, John KC, Chang, Ellen T, Chang, Gee-Chen, Chang, I-Shou, Chang, Jiang, Chang-Claude, Jenny, Chen, Chien-Jen, Chen, Chih-Yi, Chen, Chu, Chen, Chung-Hsing, Chen, Constance, Chen, Hongyan, Chen, Kexin, Chen, Kuan-Yu, Chen, Kun-Chieh, Chen, Ying, Chen, Ying-Hsiang, Chen, Yi-Song, Chen, Yuh-Min, Chien, Li-Hsin, Chirlaque, María-Dolores, Choi, Jin Eun, Choi, Yi Young, Chow, Wong-Ho, Chung, Charles C, Clavel, Jacqueline, Clavel-Chapelon, Françoise, Cocco, Pierluigi, Colt, Joanne S, Comperat, Eva, Conde, Lucia, Connors, Joseph M, Conti, David, Cortessis, Victoria K, Cotterchio, Michelle, Cozen, Wendy, Crouch, Simon, Crous-Bou, Marta, Cussenot, Olivier, and Davis, Faith G

Subjects
Humans, Neoplasms, Osteosarcoma, Bone Neoplasms, Testicular Neoplasms, Lung Neoplasms, Kidney Neoplasms, Genetic Predisposition to Disease, Tissue Array Analysis, Smoking, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, Asian Continental Ancestry Group, European Continental Ancestry Group, Female, Male, Urinary Bladder Neoplasms, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Large B-Cell, Diffuse, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Large B-Cell, Diffuse, Oncology And Carcinogenesis, Oncology & Carcinogenesis, Oncology and Carcinogenesis
Abstract

BackgroundStudies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.MethodsBetween 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers.ResultsGWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, hl (2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (ρ = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (ρ = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (ρ = 0.51, SE =0.18), and bladder and lung (ρ = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures.ConclusionOur results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.

Published
2015

3. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

Author

Wang, Zhaoming, Zhu, Bin, Zhang, Mingfeng, Parikh, Hemang, Jia, Jinping, Chung, Charles C, Sampson, Joshua N, Hoskins, Jason W, Hutchinson, Amy, Burdette, Laurie, Ibrahim, Abdisamad, Hautman, Christopher, Raj, Preethi S, Abnet, Christian C, Adjei, Andrew A, Ahlbom, Anders, Albanes, Demetrius, Allen, Naomi E, Ambrosone, Christine B, Aldrich, Melinda, Amiano, Pilar, Amos, Christopher, Andersson, Ulrika, Andriole, Gerald, Andrulis, Irene L, Arici, Cecilia, Arslan, Alan A, Austin, Melissa A, Baris, Dalsu, Barkauskas, Donald A, Bassig, Bryan A, Beane Freeman, Laura E, Berg, Christine D, Berndt, Sonja I, Bertazzi, Pier Alberto, Biritwum, Richard B, Black, Amanda, Blot, William, Boeing, Heiner, Boffetta, Paolo, Bolton, Kelly, Boutron-Ruault, Marie-Christine, Bracci, Paige M, Brennan, Paul, Brinton, Louise A, Brotzman, Michelle, Bueno-de-Mesquita, H Bas, Buring, Julie E, Butler, Mary Ann, Cai, Qiuyin, Cancel-Tassin, Geraldine, Canzian, Federico, Cao, Guangwen, Caporaso, Neil E, Carrato, Alfredo, Carreon, Tania, Carta, Angela, Chang, Gee-Chen, Chang, I-Shou, Chang-Claude, Jenny, Che, Xu, Chen, Chien-Jen, Chen, Chih-Yi, Chen, Chung-Hsing, Chen, Constance, Chen, Kuan-Yu, Chen, Yuh-Min, Chokkalingam, Anand P, Chu, Lisa W, Clavel-Chapelon, Francoise, Colditz, Graham A, Colt, Joanne S, Conti, David, Cook, Michael B, Cortessis, Victoria K, Crawford, E David, Cussenot, Olivier, Davis, Faith G, De Vivo, Immaculata, Deng, Xiang, Ding, Ti, Dinney, Colin P, Di Stefano, Anna Luisa, Diver, W Ryan, Duell, Eric J, Elena, Joanne W, Fan, Jin-Hu, Feigelson, Heather Spencer, Feychting, Maria, Figueroa, Jonine D, Flanagan, Adrienne M, Fraumeni, Joseph F, Freedman, Neal D, Fridley, Brooke L, Fuchs, Charles S, Gago-Dominguez, Manuela, Gallinger, Steven, Gao, Yu-Tang, Gapstur, Susan M, and Garcia-Closas, Montserrat

Subjects
Biological Sciences, Genetics, Cancer, Clinical Research, Human Genome, Prevention, Aetiology, 2.1 Biological and endogenous factors, Alleles, Chromosomes, Human, Pair 5, Computational Biology, DNA Methylation, Epigenesis, Genetic, Female, Gene Expression Regulation, Neoplastic, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Membrane Proteins, Neoplasm Proteins, Neoplasms, Odds Ratio, Polymorphism, Single Nucleotide, Risk, Telomerase, Medical and Health Sciences, Genetics & Heredity
Abstract

Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

Published
2014

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

Author

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

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

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

Published
2012

5. Gliomas and Farm Pesticide Exposure in Women: The Upper Midwest Health Study

Author

Carreón, Tania, Butler, Mary Ann, Ruder, Avima M., Waters, Martha A., Davis-King, Karen E., Calvert, Geoffrey M., Schulte, Paul A., Connally, Barbara, Ward, Elizabeth M., Sanderson, Wayne T., Heineman, Ellen F., Mandel, Jack S., Morton, Roscoe F., Reding, Douglas J., Rosenman, Kenneth D., and Talaska, Glenn

Published
2005

6. Priorities for Development of Research Methods in Occupational Cancer

Author

Ward, Elizabeth M., Schulte, Paul A., Bayard, Steve, Blair, Aaron, Brandt-Rauf, Paul, Butler, Mary Ann, Dankovic, David, Hubbs, Ann F., Jones, Carol, Karstadt, Myra, Kedderis, Gregory L., Melnick, Ronald, Redlich, Carrie A., Rothman, Nathaniel, Savage, Russell E., Sprinker, Michael, Toraason, Mark, and Weston, Ainsley

Published
2003

8. Joint effects between five identified risk variants, allergy, and autoimmune conditions on glioma risk

Author

Safaeian, Mahboobeh, Rajaraman, Preetha, Hartge, Patricia, Yeager, Meredith, Linet, Martha, Butler, Mary Ann, Ruder, Avima M., Purdue, Mark P., Hsing, Ann, Beane-Freeman, Laura, Hoppin, Jane A., Albanes, Demetrius, Weinstein, Stephanie J., Inskip, Peter D., Brenner, Alina, Rothman, Nathaniel, Chatterjee, Nilanjan, Gillanders, Elizabeth M., Chanock, Stephen J., and Wang, Sophia S.

Published
2013

10. Further Confirmation of Germline Glioma Risk Variant rs78378222 in TP53 and Its Implication in Tumor Tissues via Integrative Analysis of TCGA Data

Author

Wang, Zhaoming, Rajaraman, Preetha, Melin, Beatrice S., Chung, Charles C., Zhang, Weijia, McKean-Cowdin, Roberta, Michaud, Dominique, Yeager, Meredith, Ahlbom, Anders, Albanes, Demetrius, Andersson, Ulrika, Freeman, Laura Beane E., Buring, Julie E., Butler, Mary Ann, Carreón, Tania, Feychting, Maria, Gapstur, Susan M., Gaziano, Michael J., Giles, Graham G., Hallmans, Goran, Henriksson, Roger, Hoffman-Bolton, Judith, Inskip, Peter D., Kitahara, Cari M., Le Marchand, Loic, Linet, Martha S., Li, Shengchao, Peters, Ulrike, Purdue, Mark P., Rothman, Nathaniel, Ruder, Avima M., Sesso, Howard D., Severi, Gianluca, Stampfer, Meir, Stevens, Victoria L., Visvanathan, Kala, Wang, Sophia S., White, Emily, Zeleniuch-Jacquotte, Anne, Hoover, Robert, Fraumeni, Joseph F., Chatterjee, Nilanjan, Hartge, Patricia, and Chanock, Stephen J.

Published
2015
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16. Known glioma risk loci are associated with glioma with a family history of brain tumours—A case–control gene association study

Author

Melin, Beatrice, Dahlin, Anna M., Andersson, Ulrika, Wang, Zhaoming, Henriksson, Roger, Hallmans, Göran, Bondy, Melissa L., Johansen, Christoffer, Feychting, Maria, Ahlbom, Anders, Kitahara, Cari M., Wang, Sophia S., Ruder, Avima M., Carreón, Tania, Butler, Mary Ann, Inskip, Peter D., Purdue, Mark, Hsing, Ann W., Mechanic, Leah, Gillanders, Elizabeth, Yeager, Meredith, Linet, Martha, Chanock, Stephen J., Hartge, Patricia, and Rajaraman, Preetha

Published
2013
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20. Gliomas and Farm Pesticide Exposure in Men: The Upper Midwest Health Study

Author

RUDER, AVIMA M., WATERS, MARTHA A., BUTLER, MARY ANN, CARREÓN, TANIA, CALVERT, GEOFFREY M., DAVIS-KING, KAREN E., SCHULTE, PAUL A., SANDERSON, WAYNE T., WARD, ELIZABETH M., CONNALLY, L. BARBARA, HEINEMAN, ELLEN F., MANDEL, JACK S., MORTON, ROSCOE F., REDING, DOUGLAS J., ROSENMAN, KENNETH D., and TALASKA, GLENN

Published
2004

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

Author

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

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

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

Published
2015

26. Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types

Author

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

Abstract

Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.

Published
2015

27. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

Author

Machiela, Mitchell J, Zhou, Weiyin, Karlins, Eric, Sampson, Joshua N., Freedman, Neal D, Yang, Qi, Hicks, Belynda D, Dagnall, Casey, Hautman, Christopher, Jacobs, Kevin B, Abnet, Christian C, Aldrich, Melinda C., Amos, Christopher I, Amundadottir, Laufey T., Arslan, Alan A., Beane-Freeman, Laura E., Berndt, Sonja I, Black, Amanda, Blot, William J, Bock, Cathryn H., Bracci, Paige M., Brinton, Louise A, Bueno-de-Mesquita, H Bas, Burdett, Laurie, Buring, Julie E, Butler, Mary Ann, Canzian, Federico, Carreón, Tania, Chaffee, Kari G., Chang, I-Shou, Chatterjee, Nilanjan, Chen, Chu, Chen, Constance, Chen, Kexin, Chung, Charles C, Cook, Linda S, Crous Bou, Marta, Cullen, Michael, Davis, Faith G, De Vivo, Immaculata, Ding, Ti, Doherty, Jennifer, Duell, Eric J, Epstein, Caroline G., Fan, Jin Hu, Figueroa, Jonine D, Fraumeni, Joseph F., Friedenreich, Christine M., Fuchs, Charles S., Gallinger, Steven, Gao, Yu Tang, Gapstur, Susan M, García-Closas, Montserrat, Gaudet, Mia, Gaziano, J Michael, Giles, Graham, Gillanders, Elizabeth M, Giovannucci, Edward L, Goldin, Lynn, Goldstein, Alisa M, Haiman, Christopher A, Hallmans, Goran, Hankinson, Susan E, Harris, Curtis C, Henriksson, Roger, Holly, Elizabeth A., Hong, Yun Chul, Hoover, Robert N, Hsiung, Chao A, Hu, Nan, Hu, Zhuo-Wei, Hunter, David J, Hutchinson, Amy, Jenab, Mazda, Johansen, Christoffer, Khaw, Kay-Tee, Kim, Hee Nam, Kim, Yeul Hong, Kim, Young Tae, Klein, Alison P., Klein, Robert J, Koh, Woon-Puay, Kolonel, Laurence N, Kooperberg, Charles, Kraft, Peter, Krogh, Vittorio, Kurtz, Robert C., LaCroix, Andrea Z, Lan, Qing, Landi, Maria Teresa, Marchand, Loic Le, Li, Donghui, Liang, Xiaolin, Liao, Linda M., Lin, Dongxin, Liu, Jianjun, Lissowska, Jolanta, Lu, Lingeng, Magliocco, Anthony M, Malats, Núria, Matsuo, Keitaro, McNeill, Lorna H., McWilliams, Robert R., Melin, Beatrice S, Mirabello, Lisa, Moore, Lee, Olson, Sara H, Orlow, Irene, Park, Jae Yong, Patinõ-Garcia, Ana, Peplonska, Beata, Peters, Ulrike, Petersen, Gloria M., Pooler, Loreall C, Prescott, Jennifer, Prokunina-Olsson, Ludmila, Purdue, Mark P., Qiao, You Lin, Rajaraman, Preetha, Real, Francisco X., Riboli, Elio, Risch, Harvey A, Rodríguez-Santiago, Benjamín, Ruder, Avima M, Savage, Sharon A, Schumacher, Fredrick, Schwartz, Ann G., Schwartz, Kendra L., Seow, Adeline, Wendy Setiawan, Veronica, Severi, Gianluca, Shen, Hongbing, Sheng, Xin, Shin, Min Ho, Shu, Xiao-Ou, Silverman, Debra T., Spitz, Margaret R, Stevens, Victoria L, Stolzenberg-Solomon, Rachael, Stram, Daniel O, Tang, Ze Zhong, Taylor, Philip R., Teras, Lauren R., Tobias, Geoffrey S., Van Den Berg, David, Visvanathan, Kala, Wacholder, Sholom, Wang, Jiu Cun, Wang, Zhaoming, Wentzensen, Nicolas, Wheeler, William, White, Emily, Wiencke, John K, Wolpin, Brian M., Wong, Maria Pik, Wu, Chen, Wu, Tangchun, Wu, Xifeng, Wu, Yi Long, Wunder, Jay S., Xia, Lucy, Yang, Hannah P, Yang, Pan Chyr, Yu, Kai, Zanetti, Krista A., Zeleniuch-Jacquotte, Anne, Zheng, Wei, Zhou, Baosen, Ziegler, Regina G, Perez-Jurado, Luis A., Caporaso, Neil E., Rothman, Nathaniel, Tucker, Margaret A, Dean, Michael C., Yeager, Meredith, Chanock, Stephen J, Machiela, Mitchell J, Zhou, Weiyin, Karlins, Eric, Sampson, Joshua N., Freedman, Neal D, Yang, Qi, Hicks, Belynda D, Dagnall, Casey, Hautman, Christopher, Jacobs, Kevin B, Abnet, Christian C, Aldrich, Melinda C., Amos, Christopher I, Amundadottir, Laufey T., Arslan, Alan A., Beane-Freeman, Laura E., Berndt, Sonja I, Black, Amanda, Blot, William J, Bock, Cathryn H., Bracci, Paige M., Brinton, Louise A, Bueno-de-Mesquita, H Bas, Burdett, Laurie, Buring, Julie E, Butler, Mary Ann, Canzian, Federico, Carreón, Tania, Chaffee, Kari G., Chang, I-Shou, Chatterjee, Nilanjan, Chen, Chu, Chen, Constance, Chen, Kexin, Chung, Charles C, Cook, Linda S, Crous Bou, Marta, Cullen, Michael, Davis, Faith G, De Vivo, Immaculata, Ding, Ti, Doherty, Jennifer, Duell, Eric J, Epstein, Caroline G., Fan, Jin Hu, Figueroa, Jonine D, Fraumeni, Joseph F., Friedenreich, Christine M., Fuchs, Charles S., Gallinger, Steven, Gao, Yu Tang, Gapstur, Susan M, García-Closas, Montserrat, Gaudet, Mia, Gaziano, J Michael, Giles, Graham, Gillanders, Elizabeth M, Giovannucci, Edward L, Goldin, Lynn, Goldstein, Alisa M, Haiman, Christopher A, Hallmans, Goran, Hankinson, Susan E, Harris, Curtis C, Henriksson, Roger, Holly, Elizabeth A., Hong, Yun Chul, Hoover, Robert N, Hsiung, Chao A, Hu, Nan, Hu, Zhuo-Wei, Hunter, David J, Hutchinson, Amy, Jenab, Mazda, Johansen, Christoffer, Khaw, Kay-Tee, Kim, Hee Nam, Kim, Yeul Hong, Kim, Young Tae, Klein, Alison P., Klein, Robert J, Koh, Woon-Puay, Kolonel, Laurence N, Kooperberg, Charles, Kraft, Peter, Krogh, Vittorio, Kurtz, Robert C., LaCroix, Andrea Z, Lan, Qing, Landi, Maria Teresa, Marchand, Loic Le, Li, Donghui, Liang, Xiaolin, Liao, Linda M., Lin, Dongxin, Liu, Jianjun, Lissowska, Jolanta, Lu, Lingeng, Magliocco, Anthony M, Malats, Núria, Matsuo, Keitaro, McNeill, Lorna H., McWilliams, Robert R., Melin, Beatrice S, Mirabello, Lisa, Moore, Lee, Olson, Sara H, Orlow, Irene, Park, Jae Yong, Patinõ-Garcia, Ana, Peplonska, Beata, Peters, Ulrike, Petersen, Gloria M., Pooler, Loreall C, Prescott, Jennifer, Prokunina-Olsson, Ludmila, Purdue, Mark P., Qiao, You Lin, Rajaraman, Preetha, Real, Francisco X., Riboli, Elio, Risch, Harvey A, Rodríguez-Santiago, Benjamín, Ruder, Avima M, Savage, Sharon A, Schumacher, Fredrick, Schwartz, Ann G., Schwartz, Kendra L., Seow, Adeline, Wendy Setiawan, Veronica, Severi, Gianluca, Shen, Hongbing, Sheng, Xin, Shin, Min Ho, Shu, Xiao-Ou, Silverman, Debra T., Spitz, Margaret R, Stevens, Victoria L, Stolzenberg-Solomon, Rachael, Stram, Daniel O, Tang, Ze Zhong, Taylor, Philip R., Teras, Lauren R., Tobias, Geoffrey S., Van Den Berg, David, Visvanathan, Kala, Wacholder, Sholom, Wang, Jiu Cun, Wang, Zhaoming, Wentzensen, Nicolas, Wheeler, William, White, Emily, Wiencke, John K, Wolpin, Brian M., Wong, Maria Pik, Wu, Chen, Wu, Tangchun, Wu, Xifeng, Wu, Yi Long, Wunder, Jay S., Xia, Lucy, Yang, Hannah P, Yang, Pan Chyr, Yu, Kai, Zanetti, Krista A., Zeleniuch-Jacquotte, Anne, Zheng, Wei, Zhou, Baosen, Ziegler, Regina G, Perez-Jurado, Luis A., Caporaso, Neil E., Rothman, Nathaniel, Tucker, Margaret A, Dean, Michael C., Yeager, Meredith, and Chanock, Stephen J

Abstract

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.

Published
2016

28. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

Author

Wang, Zhaoming Zhu, Bin Zhang, Mingfeng Parikh, Hemang and Jia, Jinping Chung, Charles C. Sampson, Joshua N. Hoskins, Jason W. Hutchinson, Amy Burdette, Laurie Ibrahim, Abdisamad and Hautman, Christopher Raj, Preethi S. Abnet, Christian C. and Adjei, Andrew A. Ahlbom, Anders Albanes, Demetrius Allen, Naomi E. Ambrosone, Christine B. Aldrich, Melinda Amiano, Pilar Amos, Christopher Andersson, Ulrika Andriole, Jr., Gerald Andrulis, Irene L. Arici, Cecilia Arslan, Alan A. and Austin, Melissa A. Baris, Dalsu Barkauskas, Donald A. and Bassig, Bryan A. Freeman, Laura E. Beane Berg, Christine D. and Berndt, Sonja I. Bertazzi, Pier Alberto Biritwum, Richard B. and Black, Amanda Blot, William Boeing, Heiner Boffetta, Paolo and Bolton, Kelly Boutron-Ruault, Marie-Christine Bracci, Paige M. Brennan, Paul Brinton, Louise A. Brotzman, Michelle and Bueno-de-Mesquita, H. Bas Buring, Julie E. Butler, Mary Ann and Cai, Qiuyin Cancel-Tassin, Geraldine Canzian, Federico Cao, Guangwen Caporaso, Neil E. Carrato, Alfredo Carreon, Tania and Carta, Angela Chang, Gee-Chen Chang, I-Shou and Chang-Claude, Jenny Che, Xu Chen, Chien-Jen Chen, Chih-Yi and Chen, Chung-Hsing Chen, Constance Chen, Kuan-Yu Chen, Yuh-Min Chokkalingam, Anand P. Chu, Lisa W. Clavel-Chapelon, Francoise Colditz, Graham A. Colt, Joanne S. Conti, David and Cook, Michael B. Cortessis, Victoria K. Crawford, E. David and Cussenot, Olivier Davis, Faith G. De Vivo, Immaculata and Deng, Xiang Ding, Ti Dinney, Colin P. Di Stefano, Anna Luisa and Diver, W. Ryan Duell, Eric J. Elena, Joanne W. Fan, Jin-Hu Feigelson, Heather Spencer Feychting, Maria Figueroa, Jonine D. Flanagan, Adrienne M. Fraumeni, Jr., Joseph F. and Freedman, Neal D. Fridley, Brooke L. Fuchs, Charles S. and Gago-Dominguez, Manuela Gallinger, Steven Gao, Yu-Tang and Gapstur, Susan M. Garcia-Closas, Montserrat Garcia-Closas, Reina and Gastier-Foster, Julie M. Gaziano, J. Michael Gerhard, Daniela S. Giffen, Carol A. Giles, Graham G. Gillanders, Elizabeth M. Giovannucci, Edward L. Goggins, Michael Gokgoz, Nalan Goldstein, Alisa M. Gonzalez, Carlos Gorlick, Richard and Greene, Mark H. Gross, Myron Grossman, H. Barton Grubb, III, Robert Gu, Jian Guan, Peng Haiman, Christopher A. and Hallmans, Goran Hankinson, Susan E. Harris, Curtis C. and Hartge, Patricia Hattinger, Claudia Hayes, Richard B. He, Qincheng Helman, Lee Henderson, Brian E. Henriksson, Roger and Hoffman-Bolton, Judith Hohensee, Chancellor Holly, Elizabeth A. Hong, Yun-Chul Hoover, Robert N. Hosgood, H. Dean and Hsiao, Chin-Fu Hsing, Ann W. Hsiung, Chao Agnes Hu, Nan and Hu, Wei Hu, Zhibin Huang, Ming-Shyan Hunter, David J. and Inskip, Peter D. Ito, Hidemi Jacobs, Eric J. Jacobs, Kevin B. Jenab, Mazda Ji, Bu-Tian Johansen, Christoffer and Johansson, Mattias Johnson, Alison Kaaks, Rudolf Kamat, Ashish M. Kamineni, Aruna Karagas, Margaret Khanna, Chand and Khaw, Kay-Tee Kim, Christopher Kim, In-Sam Kim, Jin Hee and Kim, Yeul Hong Kim, Young-Chul Kim, Young Tae Kang, Chang Hyun Jung, Yoo Jin Kitahara, Cari M. Klein, Alison P. and Klein, Robert Kogevinas, Manolis Koh, Woon-Puay Kohno, Takashi Kolonel, Laurence N. Kooperberg, Charles Kratz, Christian P. Krogh, Vittorio Kunitoh, Hideo Kurtz, Robert C. and Kurucu, Nilgun Lan, Qing Lathrop, Mark Lau, Ching C. and Lecanda, Fernando Lee, Kyoung-Mu Lee, Maxwell P. Le Marchand, Loic Lerner, Seth P. Li, Donghui Liao, Linda M. and Lim, Wei-Yen Lin, Dongxin Lin, Jie Lindstrom, Sara and Linet, Martha S. Lissowska, Jolanta Liu, Jianjun Ljungberg, Boerje Lloreta, Josep Lu, Daru Ma, Jing Malats, Nuria and Mannisto, Satu Marina, Neyssa Mastrangelo, Giuseppe and Matsuo, Keitaro McGlynn, Katherine A. McKean-Cowdin, Roberta and McNeill, Lorna H. McWilliams, Robert R. Melin, Beatrice S. and Meltzer, Paul S. Mensah, James E. Miao, Xiaoping Michaud, Dominique S. Mondul, Alison M. Moore, Lee E. Muir, Kenneth and Niwa, Shelley Olson, Sara H. Orr, Nick Panico, Salvatore and Park, Jae Yong Patel, Alpa V. Patino-Garcia, Ana and Pavanello, Sofia Peeters, Petra H. M. Peplonska, Beata and Peters, Ulrike Petersen, Gloria M. Picci, Piero Pike, Malcolm C. Porru, Stefano Prescott, Jennifer Pu, Xia and Purdue, Mark P. Qiao, You-Lin Rajaraman, Preetha Riboli, Elio Risch, Harvey A. Rodabough, Rebecca J. Rothman, Nathaniel Ruder, Avima M. Ryu, Jeong-Seon Sanson, Marc and Schned, Alan Schumacher, Fredrick R. Schwartz, Ann G. and Schwartz, Kendra L. Schwenn, Molly Scotlandi, Katia Seow, Adeline Serra, Consol Serra, Massimo Sesso, Howard D. and Severi, Gianluca Shen, Hongbing Shen, Min Shete, Sanjay and Shiraishi, Kouya Shu, Xiao-Ou Siddiq, Afshan Sierrasesumaga, Luis Sierri, Sabina Sihoe, Alan Dart Loon Silverman, Debra T. Simon, Matthias Southey, Melissa C. Spector, Logan and Spitz, Margaret Stampfer, Meir Stattin, Par Stern, Mariana C. Stevens, Victoria L. Stolzenberg-Solomon, Rachael Z. and Stram, Daniel O. Strom, Sara S. Su, Wu-Chou Sund, Malin and Sung, Sook Whan Swerdlow, Anthony Tan, Wen Tanaka, Hideo and Tang, Wei Tang, Ze-Zhang Tardon, Adonina Tay, Evelyn and Taylor, Philip R. Tettey, Yao Thomas, David M. Tirabosco, Roberto Tjonneland, Anne Tobias, Geoffrey S. Toro, Jorge R. and Travis, Ruth C. Trichopoulos, Dimitrios Troisi, Rebecca and Truelove, Ann Tsai, Ying-Huang Tucker, Margaret A. Tumino, Rosario Van Den Berg, David Van Den Eeden, Stephen K. and Vermeulen, Roel Vineis, Paolo Visvanathan, Kala Vogel, Ulla and Wang, Chaoyu Wang, Chengfeng Wang, Junwen Wang, Sophia S. Weiderpass, Elisabete Weinstein, Stephanie J. Wentzensen, Nicolas Wheeler, William White, Emily Wiencke, John K. and Wolk, Alicja Wolpin, Brian M. Wong, Maria Pik Wrensch, Margaret Wu, Chen Wu, Tangchun Wu, Xifeng Wu, Yi-Long and Wunder, Jay S. Xiang, Yong-Bing Xu, Jun Yang, Hannah P. and Yang, Pan-Chyr Yatabe, Yasushi Ye, Yuanqing Yeboah, Edward D. Yin, Zhihua Ying, Chen Yu, Chong-Jen Yu, Kai and Yuan, Jian-Min Zanetti, Krista A. Zeleniuch-Jacquotte, Anne and Zheng, Wei Zhou, Baosen Mirabello, Lisa Savage, Sharon A. Kraft, Peter Chanock, Stephen J. Yeager, Meredith and Landi, Maria Terese Shi, Jianxin Chatterjee, Nilanjan and Amundadottir, Laufey T.

Abstract

Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 x 10(-39); Region 3: rs2853677, P = 3.30 x 10(-36) and P-Conditional = 2.36 x 10(-8); Region 4: rs2736098, P = 3.87 x 10(-12) and P-Conditional = 5.19 x 10(-6), Region 5: rs13172201, P = 0.041 and P-Conditional = 2.04 x 10(-6); and Region 6: rs10069690, P = 7.49 x 10 215 and P-Conditional = 5.35 x 10(-7)) and one in the neighboring CLPTM1L gene(Region 2: rs451360; P = 1.90 x 10(-18) and P-Conditional = 7.06 x 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

Published
2014

29. Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types

Author

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

Published
2015

30. Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types

Author

Cancer, Epi Kanker Team 1, JC onderzoeksprogramma Kanker, Sampson, Joshua N, Wheeler, William A, Yeager, Meredith, Panagiotou, Orestis, Wang, Zhaoming, Berndt, Sonja I, Lan, Qing, Abnet, Christian C, Amundadottir, Laufey T, Figueroa, Jonine D, Landi, Maria Teresa, Mirabello, Lisa, Savage, Sharon A, Taylor, Philip R, Vivo, Immaculata De, McGlynn, Katherine A, Purdue, Mark P, Rajaraman, Preetha, Adami, Hans-Olov, Ahlbom, Anders, Albanes, Demetrius, Amary, Maria Fernanda, An, She-Juan, Andersson, Ulrika, Andriole, Gerald, Andrulis, Irene L, Angelucci, Emanuele, Ansell, Stephen M, Arici, Cecilia, Armstrong, Bruce K, Arslan, Alan A, Austin, Melissa A, Baris, Dalsu, Barkauskas, Donald A, Bassig, Bryan A, Becker, Nikolaus, Benavente, Yolanda, Benhamou, Simone, Berg, Christine, Van Den Berg, David, Bernstein, Leslie, Bertrand, Kimberly A, Birmann, Brenda M, Black, Amanda, Boeing, Heiner, Boffetta, Paolo, Boutron-Ruault, Marie-Christine, Bracci, Paige M, Brinton, Louise, Brooks-Wilson, Angela R, Bueno-de-Mesquita, H Bas, Burdett, Laurie, Buring, Julie, Butler, Mary Ann, Cai, Qiuyin, Cancel-Tassin, Geraldine, Canzian, Federico, Carrato, Alfredo, Carreon, Tania, Carta, Angela, Chan, John K C, Chang, Ellen T, Chang, Gee-Chen, Chang, I-Shou, Chang, Jiang, Chang-Claude, Jenny, Chen, Chien-Jen, Chen, Chih-Yi, Chen, Chu, Chen, Chung-Hsing, Chen, Constance, Chen, Hongyan, Chen, Kexin, Chen, Kuan-Yu, Chen, Kun-Chieh, Chen, Ying, Chen, Ying-Hsiang, Chen, Yi-Song, Chen, Yuh-Min, Chien, Li-Hsin, Chirlaque, María-Dolores, Choi, Jin Eun, Choi, Yi Young, Chow, Wong-Ho, Chung, Charles C, Clavel, Jacqueline, Clavel-Chapelon, Françoise, Cocco, Pierluigi, Colt, Joanne S, Comperat, Eva, Conde, Lucia, Connors, Joseph M, Conti, David, Cortessis, Victoria K, Cotterchio, Michelle, Cozen, Wendy, Crouch, Simon, Crous-Bou, Marta, Cussenot, Olivier, Davis, Faith G, Ding, Ti, Diver, W Ryan, Dorronsoro, Miren, Dossus, Laure, Duell, Eric J, Ennas, Maria Grazia, Erickson, Ralph L, Feychting, Maria, Flanagan, Adrienne M, Foretova, Lenka, Fraumeni, Joseph F, Freedman, Neal D, Beane Freeman, Laura E, Fuchs, Charles, Gago-Dominguez, Manuela, Gallinger, Steven, Gao, Yu-Tang, Gapstur, Susan M, Garcia-Closas, Montserrat, García-Closas, Reina, Gascoyne, Randy D, Gastier-Foster, Julie, Gaudet, Mia M, Gaziano, J Michael, Giffen, Carol, Giles, Graham G, Giovannucci, Edward, Glimelius, Bengt, Goggins, Michael, Gokgoz, Nalan, Goldstein, Alisa M, Gorlick, Richard, Gross, Myron, Grubb, Robert, Gu, Jian, Guan, Peng, Gunter, Marc, Guo, Huan, Habermann, Thomas M, Haiman, Christopher A, Halai, Dina, Hallmans, Goran, Hassan, Manal, Hattinger, Claudia, He, Qincheng, He, Xingzhou, Helzlsouer, Kathy, Henderson, Brian, Henriksson, Roger, Hjalgrim, Henrik, Hoffman-Bolton, Judith, Hohensee, Chancellor, Holford, Theodore R, Holly, Elizabeth A, Hong, Yun-Chul, Hoover, Robert N, Horn-Ross, Pamela L, Hosain, G M Monawar, Hosgood, H Dean, Hsiao, Chin-Fu, Hu, Nan, Hu, Wei, Hu, Zhibin, Huang, Ming-Shyan, Huerta, Jose-Maria, Hung, Jen-Yu, Hutchinson, Amy, Inskip, Peter D, Jackson, Rebecca D, Jacobs, Eric J, Jenab, Mazda, Jeon, Hyo-Sung, Ji, Bu-Tian, Jin, Guangfu, Jin, Li, Johansen, Christoffer, Johnson, Alison, Jung, Yoo Jin, Kaaks, Rudolph, Kamineni, Aruna, Kane, Eleanor, Kang, Chang Hyun, Karagas, Margaret R, Kelly, Rachel S, Khaw, Kay-Tee, Kim, Christopher, Kim, Hee Nam, Kim, Jin Hee, Kim, Jun Suk, Kim, Yeul Hong, Kim, Young Tae, Kim, Young-Chul, Kitahara, Cari M, Klein, Alison P, Klein, Robert J, Kogevinas, Manolis, Kohno, Takashi, Kolonel, Laurence N, Kooperberg, Charles, Kricker, Anne, Krogh, Vittorio, Kunitoh, Hideo, Kurtz, Robert C, Kweon, Sun-Seog, LaCroix, Andrea, Lawrence, Charles, Lecanda, Fernando, Lee, Victor Ho Fun, Li, Donghui, Li, Haixin, Li, Jihua, Li, Yao-Jen, Li, Yuqing, Liao, Linda M, Liebow, Mark, Lightfoot, Tracy, Lim, Wei-Yen, Lin, Chien-Chung, Lin, Dongxin, Lindstrom, Sara, Linet, Martha S, Link, Brian K, Liu, Chenwei, Liu, Jianjun, Liu, Li, Ljungberg, Börje, Lloreta, Josep, Lollo, Simonetta Di, Lu, Daru, Lund, Eiluv, Malats, Nuria, Mannisto, Satu, Marchand, Loic Le, Marina, Neyssa, Masala, Giovanna, Mastrangelo, Giuseppe, Matsuo, Keitaro, Maynadie, Marc, McKay, James, McKean-Cowdin, Roberta, Melbye, Mads, Melin, Beatrice S, Michaud, Dominique S, Mitsudomi, Tetsuya, Monnereau, Alain, Montalvan, Rebecca, Moore, Lee E, Mortensen, Lotte Maxild, Nieters, Alexandra, North, Kari E, Novak, Anne J, Oberg, Ann L, Offit, Kenneth, Oh, In-Jae, Olson, Sara H, Palli, Domenico, Pao, William, Park, In Kyu, Park, Jae Yong, Park, Kyong Hwa, Patiño-Garcia, Ana, Pavanello, Sofia, Peeters, Petra H M, Perng, Reury-Perng, Peters, Ulrike, Petersen, Gloria M, Picci, Piero, Pike, Malcolm C, Porru, Stefano, Prescott, Jennifer, Prokunina-Olsson, Ludmila, Qian, Biyun, Qiao, You-Lin, Rais, Marco, Riboli, Elio, Riby, Jacques, Risch, Harvey A, Rizzato, Cosmeri, Rodabough, Rebecca, Roman, Eve, Roupret, Morgan, Ruder, Avima M, Sanjose, Silvia de, Scelo, Ghislaine, Schned, Alan, Schumacher, Fredrick, Schwartz, Kendra, Schwenn, Molly, Scotlandi, Katia, Seow, Adeline, Serra, Consol, Serra, Massimo, Sesso, Howard D, Setiawan, Veronica Wendy, Severi, Gianluca, Severson, Richard K, Shanafelt, Tait D, Shen, Hongbing, Shen, Wei, Shin, Min-Ho, Shiraishi, Kouya, Shu, Xiao-Ou, Siddiq, Afshan, Sierrasesúmaga, Luis, Sihoe, Alan Dart Loon, Skibola, Christine F, Smith, Alex, Smith, Martyn T, Southey, Melissa C, Spinelli, John J, Staines, Anthony, Stampfer, Meir, Stern, Marianna C, Stevens, Victoria L, Stolzenberg-Solomon, Rachael S, Su, Jian, Su, Wu-Chou, Sund, Malin, Sung, Jae Sook, Sung, Sook Whan, Tan, Wen, Tang, Wei, Tardón, Adonina, Thomas, David, Thompson, Carrie A, Tinker, Lesley F, Tirabosco, Roberto, Tjønneland, Anne, Travis, Ruth C, Trichopoulos, Dimitrios, Tsai, Fang-Yu, Tsai, Ying-Huang, Tucker, Margaret, Turner, Jenny, Vajdic, Claire M, Vermeulen, Roel C H, Villano, Danylo J, Vineis, Paolo, Virtamo, Jarmo, Visvanathan, Kala, Wactawski-Wende, Jean, Wang, Chaoyu, Wang, Chih-Liang, Wang, Jiu-Cun, Wang, Junwen, Wei, Fusheng, Weiderpass, Elisabete, Weiner, George J, Weinstein, Stephanie, Wentzensen, Nicolas, White, Emily, Witzig, Thomas E, Wolpin, Brian M, Wong, Maria Pik, Wu, Chen, Wu, Guoping, Wu, Junjie, Wu, Tangchun, Wu, Wei, Wu, Xifeng, Wu, Yi-Long, Wunder, Jay S, Xiang, Yong-Bing, Xu, Jun, Xu, Ping, Yang, Pan-Chyr, Yang, Tsung-Ying, Ye, Yuanqing, Yin, Zhihua, Yokota, Jun, Yoon, Ho-Il, Yu, Chong-Jen, Yu, Herbert, Yu, Kai, Yuan, Jian-Min, Zelenetz, Andrew, Zeleniuch-Jacquotte, Anne, Zhang, Xu-Chao, Zhang, Yawei, Zhao, Xueying, Zhao, Zhenhong, Zheng, Hong, Zheng, Tongzhang, Zheng, Wei, Zhou, Baosen, Zhu, Meng, Zucca, Mariagrazia, Boca, Simina M, Cerhan, James R, Ferri, Giovanni M, Hartge, Patricia, Hsiung, Chao Agnes, Magnani, Corrado, Miligi, Lucia, Morton, Lindsay M, Smedby, Karin E, Teras, Lauren R, Vijai, Joseph, Wang, Sophia S, Brennan, Paul, Caporaso, Neil E, Hunter, David J, Kraft, Peter, Rothman, Nathaniel, Silverman, Debra T, Slager, Susan L, Chanock, Stephen J, Chatterjee, Nilanjan, Cancer, Epi Kanker Team 1, JC onderzoeksprogramma Kanker, Sampson, Joshua N, Wheeler, William A, Yeager, Meredith, Panagiotou, Orestis, Wang, Zhaoming, Berndt, Sonja I, Lan, Qing, Abnet, Christian C, Amundadottir, Laufey T, Figueroa, Jonine D, Landi, Maria Teresa, Mirabello, Lisa, Savage, Sharon A, Taylor, Philip R, Vivo, Immaculata De, McGlynn, Katherine A, Purdue, Mark P, Rajaraman, Preetha, Adami, Hans-Olov, Ahlbom, Anders, Albanes, Demetrius, Amary, Maria Fernanda, An, She-Juan, Andersson, Ulrika, Andriole, Gerald, Andrulis, Irene L, Angelucci, Emanuele, Ansell, Stephen M, Arici, Cecilia, Armstrong, Bruce K, Arslan, Alan A, Austin, Melissa A, Baris, Dalsu, Barkauskas, Donald A, Bassig, Bryan A, Becker, Nikolaus, Benavente, Yolanda, Benhamou, Simone, Berg, Christine, Van Den Berg, David, Bernstein, Leslie, Bertrand, Kimberly A, Birmann, Brenda M, Black, Amanda, Boeing, Heiner, Boffetta, Paolo, Boutron-Ruault, Marie-Christine, Bracci, Paige M, Brinton, Louise, Brooks-Wilson, Angela R, Bueno-de-Mesquita, H Bas, Burdett, Laurie, Buring, Julie, Butler, Mary Ann, Cai, Qiuyin, Cancel-Tassin, Geraldine, Canzian, Federico, Carrato, Alfredo, Carreon, Tania, Carta, Angela, Chan, John K C, Chang, Ellen T, Chang, Gee-Chen, Chang, I-Shou, Chang, Jiang, Chang-Claude, Jenny, Chen, Chien-Jen, Chen, Chih-Yi, Chen, Chu, Chen, Chung-Hsing, Chen, Constance, Chen, Hongyan, Chen, Kexin, Chen, Kuan-Yu, Chen, Kun-Chieh, Chen, Ying, Chen, Ying-Hsiang, Chen, Yi-Song, Chen, Yuh-Min, Chien, Li-Hsin, Chirlaque, María-Dolores, Choi, Jin Eun, Choi, Yi Young, Chow, Wong-Ho, Chung, Charles C, Clavel, Jacqueline, Clavel-Chapelon, Françoise, Cocco, Pierluigi, Colt, Joanne S, Comperat, Eva, Conde, Lucia, Connors, Joseph M, Conti, David, Cortessis, Victoria K, Cotterchio, Michelle, Cozen, Wendy, Crouch, Simon, Crous-Bou, Marta, Cussenot, Olivier, Davis, Faith G, Ding, Ti, Diver, W Ryan, Dorronsoro, Miren, Dossus, Laure, Duell, Eric J, Ennas, Maria Grazia, Erickson, Ralph L, Feychting, Maria, Flanagan, Adrienne M, Foretova, Lenka, Fraumeni, Joseph F, Freedman, Neal D, Beane Freeman, Laura E, Fuchs, Charles, Gago-Dominguez, Manuela, Gallinger, Steven, Gao, Yu-Tang, Gapstur, Susan M, Garcia-Closas, Montserrat, García-Closas, Reina, Gascoyne, Randy D, Gastier-Foster, Julie, Gaudet, Mia M, Gaziano, J Michael, Giffen, Carol, Giles, Graham G, Giovannucci, Edward, Glimelius, Bengt, Goggins, Michael, Gokgoz, Nalan, Goldstein, Alisa M, Gorlick, Richard, Gross, Myron, Grubb, Robert, Gu, Jian, Guan, Peng, Gunter, Marc, Guo, Huan, Habermann, Thomas M, Haiman, Christopher A, Halai, Dina, Hallmans, Goran, Hassan, Manal, Hattinger, Claudia, He, Qincheng, He, Xingzhou, Helzlsouer, Kathy, Henderson, Brian, Henriksson, Roger, Hjalgrim, Henrik, Hoffman-Bolton, Judith, Hohensee, Chancellor, Holford, Theodore R, Holly, Elizabeth A, Hong, Yun-Chul, Hoover, Robert N, Horn-Ross, Pamela L, Hosain, G M Monawar, Hosgood, H Dean, Hsiao, Chin-Fu, Hu, Nan, Hu, Wei, Hu, Zhibin, Huang, Ming-Shyan, Huerta, Jose-Maria, Hung, Jen-Yu, Hutchinson, Amy, Inskip, Peter D, Jackson, Rebecca D, Jacobs, Eric J, Jenab, Mazda, Jeon, Hyo-Sung, Ji, Bu-Tian, Jin, Guangfu, Jin, Li, Johansen, Christoffer, Johnson, Alison, Jung, Yoo Jin, Kaaks, Rudolph, Kamineni, Aruna, Kane, Eleanor, Kang, Chang Hyun, Karagas, Margaret R, Kelly, Rachel S, Khaw, Kay-Tee, Kim, Christopher, Kim, Hee Nam, Kim, Jin Hee, Kim, Jun Suk, Kim, Yeul Hong, Kim, Young Tae, Kim, Young-Chul, Kitahara, Cari M, Klein, Alison P, Klein, Robert J, Kogevinas, Manolis, Kohno, Takashi, Kolonel, Laurence N, Kooperberg, Charles, Kricker, Anne, Krogh, Vittorio, Kunitoh, Hideo, Kurtz, Robert C, Kweon, Sun-Seog, LaCroix, Andrea, Lawrence, Charles, Lecanda, Fernando, Lee, Victor Ho Fun, Li, Donghui, Li, Haixin, Li, Jihua, Li, Yao-Jen, Li, Yuqing, Liao, Linda M, Liebow, Mark, Lightfoot, Tracy, Lim, Wei-Yen, Lin, Chien-Chung, Lin, Dongxin, Lindstrom, Sara, Linet, Martha S, Link, Brian K, Liu, Chenwei, Liu, Jianjun, Liu, Li, Ljungberg, Börje, Lloreta, Josep, Lollo, Simonetta Di, Lu, Daru, Lund, Eiluv, Malats, Nuria, Mannisto, Satu, Marchand, Loic Le, Marina, Neyssa, Masala, Giovanna, Mastrangelo, Giuseppe, Matsuo, Keitaro, Maynadie, Marc, McKay, James, McKean-Cowdin, Roberta, Melbye, Mads, Melin, Beatrice S, Michaud, Dominique S, Mitsudomi, Tetsuya, Monnereau, Alain, Montalvan, Rebecca, Moore, Lee E, Mortensen, Lotte Maxild, Nieters, Alexandra, North, Kari E, Novak, Anne J, Oberg, Ann L, Offit, Kenneth, Oh, In-Jae, Olson, Sara H, Palli, Domenico, Pao, William, Park, In Kyu, Park, Jae Yong, Park, Kyong Hwa, Patiño-Garcia, Ana, Pavanello, Sofia, Peeters, Petra H M, Perng, Reury-Perng, Peters, Ulrike, Petersen, Gloria M, Picci, Piero, Pike, Malcolm C, Porru, Stefano, Prescott, Jennifer, Prokunina-Olsson, Ludmila, Qian, Biyun, Qiao, You-Lin, Rais, Marco, Riboli, Elio, Riby, Jacques, Risch, Harvey A, Rizzato, Cosmeri, Rodabough, Rebecca, Roman, Eve, Roupret, Morgan, Ruder, Avima M, Sanjose, Silvia de, Scelo, Ghislaine, Schned, Alan, Schumacher, Fredrick, Schwartz, Kendra, Schwenn, Molly, Scotlandi, Katia, Seow, Adeline, Serra, Consol, Serra, Massimo, Sesso, Howard D, Setiawan, Veronica Wendy, Severi, Gianluca, Severson, Richard K, Shanafelt, Tait D, Shen, Hongbing, Shen, Wei, Shin, Min-Ho, Shiraishi, Kouya, Shu, Xiao-Ou, Siddiq, Afshan, Sierrasesúmaga, Luis, Sihoe, Alan Dart Loon, Skibola, Christine F, Smith, Alex, Smith, Martyn T, Southey, Melissa C, Spinelli, John J, Staines, Anthony, Stampfer, Meir, Stern, Marianna C, Stevens, Victoria L, Stolzenberg-Solomon, Rachael S, Su, Jian, Su, Wu-Chou, Sund, Malin, Sung, Jae Sook, Sung, Sook Whan, Tan, Wen, Tang, Wei, Tardón, Adonina, Thomas, David, Thompson, Carrie A, Tinker, Lesley F, Tirabosco, Roberto, Tjønneland, Anne, Travis, Ruth C, Trichopoulos, Dimitrios, Tsai, Fang-Yu, Tsai, Ying-Huang, Tucker, Margaret, Turner, Jenny, Vajdic, Claire M, Vermeulen, Roel C H, Villano, Danylo J, Vineis, Paolo, Virtamo, Jarmo, Visvanathan, Kala, Wactawski-Wende, Jean, Wang, Chaoyu, Wang, Chih-Liang, Wang, Jiu-Cun, Wang, Junwen, Wei, Fusheng, Weiderpass, Elisabete, Weiner, George J, Weinstein, Stephanie, Wentzensen, Nicolas, White, Emily, Witzig, Thomas E, Wolpin, Brian M, Wong, Maria Pik, Wu, Chen, Wu, Guoping, Wu, Junjie, Wu, Tangchun, Wu, Wei, Wu, Xifeng, Wu, Yi-Long, Wunder, Jay S, Xiang, Yong-Bing, Xu, Jun, Xu, Ping, Yang, Pan-Chyr, Yang, Tsung-Ying, Ye, Yuanqing, Yin, Zhihua, Yokota, Jun, Yoon, Ho-Il, Yu, Chong-Jen, Yu, Herbert, Yu, Kai, Yuan, Jian-Min, Zelenetz, Andrew, Zeleniuch-Jacquotte, Anne, Zhang, Xu-Chao, Zhang, Yawei, Zhao, Xueying, Zhao, Zhenhong, Zheng, Hong, Zheng, Tongzhang, Zheng, Wei, Zhou, Baosen, Zhu, Meng, Zucca, Mariagrazia, Boca, Simina M, Cerhan, James R, Ferri, Giovanni M, Hartge, Patricia, Hsiung, Chao Agnes, Magnani, Corrado, Miligi, Lucia, Morton, Lindsay M, Smedby, Karin E, Teras, Lauren R, Vijai, Joseph, Wang, Sophia S, Brennan, Paul, Caporaso, Neil E, Hunter, David J, Kraft, Peter, Rothman, Nathaniel, Silverman, Debra T, Slager, Susan L, Chanock, Stephen J, and Chatterjee, Nilanjan

Published
2015

31. Further Confirmation of Germline Glioma Risk Variant rs78378222 inTP53and Its Implication in Tumor Tissues via Integrative Analysis of TCGA Data

Author

Wang, Zhaoming, primary, Rajaraman, Preetha, additional, Melin, Beatrice S., additional, Chung, Charles C., additional, Zhang, Weijia, additional, McKean-Cowdin, Roberta, additional, Michaud, Dominique, additional, Yeager, Meredith, additional, Ahlbom, Anders, additional, Albanes, Demetrius, additional, Andersson, Ulrika, additional, Freeman, Laura E. Beane, additional, Buring, Julie E., additional, Butler, Mary Ann, additional, Carreón, Tania, additional, Feychting, Maria, additional, Gapstur, Susan M., additional, Gaziano, J. Michael, additional, Giles, Graham G., additional, Hallmans, Goran, additional, Henriksson, Roger, additional, Hoffman-Bolton, Judith, additional, Inskip, Peter D., additional, Kitahara, Cari M., additional, Marchand, Loic Le, additional, Linet, Martha S., additional, Li, Shengchao, additional, Peters, Ulrike, additional, Purdue, Mark P., additional, Rothman, Nathaniel, additional, Ruder, Avima M., additional, Sesso, Howard D., additional, Severi, Gianluca, additional, Stampfer, Meir, additional, Stevens, Victoria L., additional, Visvanathan, Kala, additional, Wang, Sophia S., additional, White, Emily, additional, Zeleniuch-Jacquotte, Anne, additional, Hoover, Robert, additional, Fraumeni, Joseph F., additional, Chatterjee, Nilanjan, additional, Hartge, Patricia, additional, and Chanock, Stephen J., additional

Published
2015
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33. Known glioma risk loci are associated with glioma with a family history of brain tumours:a case-control gene association study

Author

Melin, Beatrice, Dahlin, Anna M, Andersson, Ulrika, Wang, Zhaoming, Henriksson, Roger, Hallmans, Göran, Bondy, Melissa L, Johansen, Christoffer, Feychting, Maria, Ahlbom, Anders, Kitahara, Cari M, Wang, Sophia S, Ruder, Avima M, Carreón, Tania, Butler, Mary Ann, Inskip, Peter D, Purdue, Mark, Hsing, Ann W, Mechanic, Leah, Gillanders, Elizabeth, Yeager, Meredith, Linet, Martha, Chanock, Stephen J, Hartge, Patricia, Rajaraman, Preetha, Melin, Beatrice, Dahlin, Anna M, Andersson, Ulrika, Wang, Zhaoming, Henriksson, Roger, Hallmans, Göran, Bondy, Melissa L, Johansen, Christoffer, Feychting, Maria, Ahlbom, Anders, Kitahara, Cari M, Wang, Sophia S, Ruder, Avima M, Carreón, Tania, Butler, Mary Ann, Inskip, Peter D, Purdue, Mark, Hsing, Ann W, Mechanic, Leah, Gillanders, Elizabeth, Yeager, Meredith, Linet, Martha, Chanock, Stephen J, Hartge, Patricia, and Rajaraman, Preetha

Published
2013

34. Risk factors for oligodendroglial tumors : A pooled international study

Author

McCarthy, Bridget J, Rankin, Kristin M, Aldape, Ken, Bondy, Melissa L, Brännström, Thomas, Broholm, Helle, Feychting, Maria, Il'yasova, Dora, Inskip, Peter D, Johansen, Christoffer, Melin, Beatrice, Ruder, Avima M, Butler, Mary Ann, Scheurer, Michael E, Schüz, Joachim, Schwartzbaum, Judith A, Wrensch, Margaret R, Davis, Faith G, McCarthy, Bridget J, Rankin, Kristin M, Aldape, Ken, Bondy, Melissa L, Brännström, Thomas, Broholm, Helle, Feychting, Maria, Il'yasova, Dora, Inskip, Peter D, Johansen, Christoffer, Melin, Beatrice, Ruder, Avima M, Butler, Mary Ann, Scheurer, Michael E, Schüz, Joachim, Schwartzbaum, Judith A, Wrensch, Margaret R, and Davis, Faith G

Abstract

Oligodendroglial tumors are rare subtypes of brain tumors and are often combined with other glial tumors in epidemiological analyses. However, different demographic associations and clinical characteristics suggest potentially different risk factors. The purpose of this study was to investigate possible risk factors for oligodendroglial tumors (including oligodendroglioma, anaplastic oligodendroglioma, and mixed glioma). Data from 7 case-control studies (5 US and 2 Scandinavian) were pooled. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age group, gender, and study site. Data on 617 cases and 1260 controls were available for analyses. Using data from all 7 studies, history of allergies and/or asthma was associated with a decreased risk of anaplastic oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9), and history of asthma only was associated with a decreased risk of oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) and anaplastic oligodendroglioma (OR = 0.3; 95% CI: 0.1-0.9). A family history of brain tumors was associated with an increased risk of anaplastic oligodendroglioma (OR = 2.2; 95% CI: 1.1-4.5). Having had chicken pox was associated with a decreased risk of oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9) and anaplastic oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) in the US studies. Although there is some overlap in risk factors between oligodendroglial tumors and gliomas as a group, it is likely that additional factors specific to oligodendroglial tumors have yet to be identified. Large, multi-institution international studies will be necessary to better characterize these etiological risk factors.

Published
2011
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35. Known glioma risk loci are associated with glioma with a family history of brain tumours-A case-control gene association study

Author

Melin, Beatrice, primary, Dahlin, Anna M., additional, Andersson, Ulrika, additional, Wang, Zhaoming, additional, Henriksson, Roger, additional, Hallmans, Göran, additional, Bondy, Melissa L., additional, Johansen, Christoffer, additional, Feychting, Maria, additional, Ahlbom, Anders, additional, Kitahara, Cari M., additional, Wang, Sophia S., additional, Ruder, Avima M., additional, Carreón, Tania, additional, Butler, Mary Ann, additional, Inskip, Peter D., additional, Purdue, Mark, additional, Hsing, Ann W., additional, Mechanic, Leah, additional, Gillanders, Elizabeth, additional, Yeager, Meredith, additional, Linet, Martha, additional, Chanock, Stephen J., additional, Hartge, Patricia, additional, and Rajaraman, Preetha, additional

Published
2012
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36. Detection of DNA damage in workers exposed to JP-8 jet fuel

Author

Krieg, Edward F., primary, Mathias, Patricia I., additional, Toennis, Christine A., additional, Clark, John C., additional, Marlow, Kate L., additional, B’Hymer, Clayton, additional, Singh, Narendra P., additional, Gibson, Roger L., additional, and Butler, Mary Ann, additional

Published
2012
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39. The utility of naphthyl-keratin adducts as biomarkers for jet-fuel exposure

Author

Kang-Sickel, Juei-Chuan C., primary, Butler, Mary Ann, additional, Frame, Lynn, additional, Serdar, Berrin, additional, Chao, Yi-Chun E., additional, Egeghy, Peter, additional, Rappaport, Stephen M., additional, Toennis, Christine A., additional, Li, Wang, additional, Borisova, Tatyana, additional, French, John E., additional, and Nylander-French, Leena A., additional

Published
2011
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44. Common Variation in Genes Related to Innate Immunity and Risk of Adult Glioma

Author

Rajaraman, Preetha, primary, Brenner, Alina V., additional, Butler, Mary Ann, additional, Wang, Sophia S., additional, Pfeiffer, Ruth M., additional, Ruder, Avima M., additional, Linet, Martha S., additional, Yeager, Meredith, additional, Wang, Zhaoming, additional, Orr, Nick, additional, Fine, Howard A., additional, Kwon, Deukwoo, additional, Thomas, Gilles, additional, Rothman, Nathaniel, additional, Inskip, Peter D., additional, and Chanock, Stephen J., additional

Published
2009
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45. Synthesis, characterization, and use of 2-[(2H9)butoxy]acetic acid and 2-(3-methylbutoxy)acetic acid as an internal standard and an instrument performance surrogate, respectively, for the gas chromatographic–mass spectrometric determination of 2-butoxyacetic acid, a human metabolite of 2-butoxyethanol

Author

Brown, Kenneth K., primary, Cheever, Kenneth L., additional, Butler, Mary Ann, additional, Shaw, Peter B., additional, and McLaurin, Jeffery L., additional

Published
2003
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47. Semi-quantitative analysis of influenza samples using the Luminex xTAG® respiratory viral panel kit.

Author

Smith, Jerome, Sammons, Deborah, Toennis, Christine, Butler, Mary Ann, Blachere, Francoise, and Beezhold, Donald

Subjects
INFLUENZA A virus, RESPIRATION, INFLUENZA vaccines, QUANTITATIVE research, NUCLEIC acids, INFLUENZA A virus, H1N1 subtype, DNA, GENE amplification
Abstract

The Luminex xTAG® respiratory viral panel (RVP) kit simultaneously detects and identifies multiple respiratory viruses including several subtypes of influenza A using a multiplex nucleic acid amplification test assay platform. The emitted fluorescence signal from the RVP assay provides qualitative information on the presence of a particular viral species in respiratory specimens. However, a quantitative assessment is preferred when monitoring environmental samples for respiratory viruses. In this study, we explored the potential use of the RVP kit as a semi-quantitative screening assay for influenza virus detection. The concentration- response of the RVP assay was modeled using four-parameter logistic (4-PL) fits of mean fluorescence intensity (MFI) versus dilute ranges of the influenza A matrix gene, seasonal influenza vaccine, and 2009 H1N1 influenza vaccine. The goodness of fit of the 4-PL model was evaluated by comparing the copy number determined with the fitted model (observed copy number) with the copy number calculated from the dilution of the matrix DNA or vaccine (expected copy number). For the matrix DNA and 2009 H1N1 vaccine, the 4-PL model provided good fit for the influenza A RVP assay response over factors of 103 to 104. For seasonal influenza vaccine, the model provided good fit for RVP assay response to influenza A, influenza B, H1, and H3. [ABSTRACT FROM AUTHOR]

Published
2012
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48. Risk factors for oligodendroglial tumors: A pooled international study.

Author

McCarthy, Bridget J., Rankin, Kristin M., Aldape, Ken, Bondy, Melissa L., Brännström, Thomas, Broholm, Helle, Feychting, Maria, Il'yasova, Dora, Inskip, Peter D., Johansen, Christoffer, Melin, Beatrice S., Ruder, Avima M., Butler, Mary Ann, Scheurer, Michael E., Schüz, Joachim, Schwartzbaum, Judith A., Wrensch, Margaret R., and Davis, Faith G.

Published
2011
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50. Comparison and evaluation of analysis procedures for the quantification of (2-methoxyethoxy)acetic acid in urine.

Author

B'Hymer, Clayton, Butler, Mary Ann, and Cheever, Kenneth L.

Subjects
*ACETIC acid, *URINE, *GLYCOLS, *ALCOHOL, *FATTY acids
Abstract

Several extraction and derivatization procedures were evaluated for the quantification of (2-methoxyethoxy)acetic acid (MEAA) in urine. MEAA is a metabolite and a biomarker for exposure to 2-(2-methoxyethoxy)ethanol, a glycol ether with widespread use in various industrial applications and the specific use as an anti-icing additive in the military jet fuel formulation JP-8. Quantification of glycol ether biomarkers is an active area of analytical research. Various sample preparation procedures were evaluated: liquid–liquid extraction (LLE) using ethyl acetate yielded the highest recovery, and solid-phase extraction (SPE) gave low recovery of MEAA. Two derivatization procedures were thoroughly investigated and validated, namely, silylation of MEAA with N-methyl- N-( tert-butyldimethylsilyl)trifluoroacetamide (MTBSTFA), and esterification of MEAA using ethanol. Quantification was performed by gas chromatography (GC) with a mass spectrometer as detector and using a polydimethylsiloxane (HP-1) capillary column. Deuterated 2-butoxyacetic acid (d-BAA) was used as an internal standard. Recovery studies of spiked human urine demonstrated the accuracy and precision of both procedures. The limit of detection (LOD) and other figures of merit for both derivatization procedures will be discussed in detail. Applications of these analysis procedures are also discussed. [ABSTRACT FROM AUTHOR]

Published
2005
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