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10 results on '"Wactawski-Wende, J."'

1. Associations between toxic metals and reproductive hormones modified by specific food intakes among healthy premenopausal women

Author

Anna Z. Pollack, Mumford S, Freeman J, Kim K, Purdue-Smithe A, Wactawski-Wende J, Radoc J, Andriessen, Carrie J. Nobles, and Alkhalaf Z

Subjects
Global and Planetary Change, Food intake, Epidemiology, business.industry, Health, Toxicology and Mutagenesis, Environmental health, Reproductive hormones, Public Health, Environmental and Occupational Health, Medicine, business, Pollution
Published
2019
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2. Functional characterization of a multi-cancer risk locus on chr5p15.33 reveals regulation of TERT by ZNF148

Author

Fang, J, Jia, J, Makowski, M, Xu, M, Wang, Z, Zhang, T, Hoskins, Jw, Choi, J, Han, Y, Zhang, M, Thomas, J, Kovacs, M, Collins, I, Dzyadyk, M, Thompson, A, O'Neill, M, Das, S, Lan, Q, Koster, R, Solomon, Rs, Kraft, P, Wolpin, Bm, Jansen, Pwtc, Olson, S, Mcglynn, Ka, Kanetsky, Pa, Chatterjee, N, Barrett, Jh, Dunning, Am, Taylor, Jc, Newton Bishop, Ja, Bishop, Dt, Andresson, T, Petersen, Gm, Amos, Ci, Iles, Mm, Nathanson, Kl, Landi, Mt, Vermeulen, M, Brown, Km, Amundadottir, Lt, Canzian, F, Kooperberg, C, Arslan, Aa, Bracci, Pm, Buring, J, Duell, Ej, Gallinger, S, Jacobs, Ej, Kamineni, A, Van Den Eeden, S, Klein, Ap, Kolonel, Ln, Li, D, Olson, Sh, Risch, Ha, Sesso, Hd, Visvanathan, K, Zheng, W, Albanes, D, Austin, Ma, Boutron Ruault, Mc, Bueno de Mesquita, Hb, Cotterchio, M, Gaziano, Jm, Giovannucci, El, Goggins, M, Gross, M, Hassan, M, Helzlsouer, Kj, Holly, Ea, Hunter, Dj, Jenab, M, Kaaks, R, Key, Tj, Khaw, Kt, Krogh, V, Kurtz, Rc, Lacroix, A, Le Marchand, L, Mannisto, S, Patel, Av, Peeters, Phm, Riboli, E, Shu, Xo, Sund, M, Thornquist, M, Tjønneland, A, Tobias, Gs, Trichopoulos, D, Wactawski Wende, J, Yu, H, Yu, K, Zeleniuch Jacquotte, A, Hoover, R, Hartge, P, Fuchs, C, Chanock, Sj, Stevens, V, Caporaso, Ne, Brennan, P, Mckay, J, Wu, X, Hung, Rj, Mclaughlin, Jr, Bickeboller, H, Risch, A, Wichmann, E, Houlston, R, Mann, G, Hopper, J, Aitken, J, Armstrong, B, Giles, G, Holland, E, Kefford, R, Cust, A, Jenkins, M, Schmid, H, Puig, S, Aguilera, P, Badenas, C, Barreiro, A, Carrera, C, Gabriel, D, Xavier, Pg, Iglesias Garcia, P, Malvehy, J, Mila, M, Pigem, R, Potrony, M, Batille, Ja, Marti, Gt, Hayward, N, Martin, N, Montgomery, G, Duffy, D, Whiteman, D, Gregor, Sm, Calista, D, Landi, G, Minghetti, P, Arcangeli, F, Bertazzi, Pa, Ghiorzo, Paola, Bianchi, Giovanna, Pastorino, Lorenza, Bruno, William, Andreotti, Virginia, Queirolo, P, Spagnolo, Francesco, Mackie, R, Lang, J, Gruis, N, van Nieuwpoort, Fa, Out, C, Bergman, W, Kukutsch, N, Bavinck, Jnb, Bakker, B, van der Stoep, N, Ter Huurne, J, van der Rhee, H, Bekkenk, M, Snels, D, van Praag, M, Brochez, L, Gerritsen, R, Crijns, M, Vasen, H, Janssen, B, Ingvar, C, Olsson, H, Jonsson, G, Borg, A, Harbst, K, Nielsen, K, Zander, As, Molvern, A, Helsing, P, Andresen, Pa, Rootwelt, H, Akslen, La, Bressac de Paillerets, B, Demenais, F, Avril, Mf, Chaudru, V, Jeannin, P, Lesueur, F, Maubec, E, Mohamdi, H, Bossard, M, Vaysse, A, Boitier, F, Caron, O, Caux, F, Dalle, S, Dereure, O, Leroux, D, Martin, L, Mateus, C, Robert, C, Stoppa Lyonnet, D, Thomas, L, Wierzbicka, E, Elder, D, Ming, M, Mitra, N, Debniak, T, Lubinski, J, Hocevar, M, Novakovic, S, Peric, B, Skerl, P, Hansson, J, Hoiom, V, Freidman, E, Azizi, E, Baron Epel, O, Scope, A, Pavlotsky, F, Cohen Manheim, I, Laitman, Y, Harland, M, Randerson Moor, J, Laye, J, Davies, J, Nsengimana, J, O'Shea, S, Chan, M, Gascoyne, J, Tucker, Ma, Goldstein, Am, and Yang, X. r.

Subjects
0301 basic medicine, Male, Lung Neoplasms, Skin Neoplasms, General Physics and Astronomy, Genome-wide association study, VARIANTS, Histones, Skin cancer, RNA, Small Interfering, Melanoma, Telomerase, GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries), Pancreas cancer, Regulation of gene expression, Genetics, Zinc finger, Gene knockdown, Multidisciplinary, Proteomics and Chromatin Biology, TRICL Consortium, Chromosome Mapping, GenoMEL Consortium, PANCREATIC-CANCER, Multidisciplinary Sciences, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Science & Technology - Other Topics, Chromosomes, Human, Pair 5, Female, Lung cancer, Signal Transduction, SUSCEPTIBILITY LOCI, Science, Locus (genetics), Single-nucleotide polymorphism, PROMOTES GROWTH, Biology, Polymorphism, Single Nucleotide, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, LUNG-CANCER, Testicular Neoplasms, Cell Line, Tumor, MD Multidisciplinary, Humans, Genetic Predisposition to Disease, QUANTITATIVE PROTEOMICS, GENOME-WIDE ASSOCIATION, Gene, PanScan Consortium, Càncer de pell, Càncer de pàncrees, Alleles, Science & Technology, Kirurgi, HUMAN-CELLS, Telomere Homeostasis, Correction, General Chemistry, Molecular biology, TERT-CLPTM1L LOCUS, Telomere, Pancreatic Neoplasms, 030104 developmental biology, Genetic Loci, TELOMERE LENGTH, Càncer de pulmó, Surgery, Genètica, Genome-Wide Association Study, Transcription Factors
Abstract

Genome wide association studies (GWAS) have mapped multiple independent cancer susceptibility loci to chr5p15.33. Here, we show that fine-mapping of pancreatic and testicular cancer GWAS within one of these loci (Region 2 in CLPTM1L) focuses the signal to nine highly correlated SNPs. Of these, rs36115365-C associated with increased pancreatic and testicular but decreased lung cancer and melanoma risk, and exhibited preferred protein-binding and enhanced regulatory activity. Transcriptional gene silencing of this regulatory element repressed TERT expression in an allele-specific manner. Proteomic analysis identifies allele-preferred binding of Zinc finger protein 148 (ZNF148) to rs36115365-C, further supported by binding of purified recombinant ZNF148. Knockdown of ZNF148 results in reduced TERT expression, telomerase activity and telomere length. Our results indicate that the association with chr5p15.33-Region 2 may be explained by rs36115365, a variant influencing TERT expression via ZNF148 in a manner consistent with elevated TERT in carriers of the C allele., Genetic variants at multiple loci of chr5p15.33 have been associated with susceptibility to numerous cancers. Here the authors show that the association of one of these loci may be explained by a variant, rs36115365, influencing telomerase reverse transcriptase (TERT) expression via ZNF148.

Published
2017

3. Calcium plus vitamin D supplementation and the risk of colorectal cancer: Commentary

Author

Wactawski-Wende, J, Kotchen, JM, Anderson, GL, Assaf, AR, Brunner, RL, O'sullivan, MJ, Margolis, KL, Ockene, JK, Phillips, L, Pottern, L, Prentice, RL, Robbins, J, Rohan, TE, Sarto, GE, Sharma, S, Stefanick, ML, Van Horn, L, Wallace, RB, Whitlock, E, Bassford, T, Beresford, SAA, Black, HR, Bonds, DE, Brzyski, RG, Caan, B, Chlebowski, RT, Cochrane, B, Garland, C, Gass, M, Hays, J, Heiss, G, Hendrix, SL, Howard, BV, Hsia, J, Hubbell, FA, Jackson, RD, Johnson, KC, Judd, H, Kooperberg, CL, Kuller, LH, Lacroix, AZ, Lane, DS, Langer, RD, Lasser, NL, Lewis, CE, Limacher, MC, and Manson, JE

Subjects
Aging, Prevention, Clinical Trials and Supportive Activities, Colo-Rectal Cancer, Paediatrics and Reproductive Medicine, Complementary and Alternative Medicine, Clinical Research, 6.1 Pharmaceuticals, Biomedical Imaging, Digestive Diseases, 3.3 Nutrition and chemoprevention, Obstetrics & Reproductive Medicine, Nutrition, Cancer
Published
2006

7. Oral bisphosphonate use and lung cancer incidence among postmenopausal women

Author

Paolo Boffetta, Jane A. Cauley, Jean Wactawski-Wende, S. Chen, Gloria E. Sarto, Xiaodan Mai, Karen C. Johnson, Jo L. Freudenheim, Heather A. Wakelee, Meng-Hua Tao, Tao, Meng-Hua, Chen, S., Freudenheim, J.L., Cauley, J.A., Johnson, K.C., Mai, X., Sarto, G.E., Wakelee, H., Boffetta, P., and Wactawski-Wende, J.

Subjects
medicine.medical_specialty, Lung Neoplasms, Epidemiology, medicine.medical_treatment, Osteoporosis, Administration, Oral, 030209 endocrinology & metabolism, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Bisphosphonate, Humans, Prospective Studies, Prospective cohort study, Lung cancer, Aged, Randomized Controlled Trials as Topic, Bone Density Conservation Agents, Diphosphonates, business.industry, Endometrial cancer, Incidence (epidemiology), Women's Health Initiative, Women's health initiative, Incidence, Hematology, Middle Aged, medicine.disease, Prognosis, Postmenopausal women, United States, Postmenopause, Observational Studies as Topic, Oncology, 030220 oncology & carcinogenesis, Women's Health, Female, business
Abstract

Background Bisphosphonates are common medications for the treatment of osteoporosis in older populations. Several studies, including the Women’s Health Initiative (WHI), have found inverse associations of bisphosphonate use with risk of breast and endometrial cancer, but little is known about its association with other common malignancies. The objective of this study was to evaluate the association of bisphosphonate use on the incidence of lung cancer in the WHI. Patients and methods The association between oral bisphosphonate use and lung cancer risk was examined in 151 432 postmenopausal women enrolled into the WHI in 1993–1998. At baseline and during follow-up, participants completed an inventory of regularly used medications including bisphosphonates. Results After a mean follow-up of 13.3 years, 2511 women were diagnosed with incident lung cancer. There was no evidence of a difference in lung cancer incidence between oral bisphosphonate users and never users (adjusted hazard ratio = 0.91; 95% confidence intervals, 0.80–1.04; P = 0.16). However, an inverse association was observed among those who were never smokers (hazard ratio = 0.57, 95% confidence interval, 0.39–0.84; P Conclusion In this large prospective cohort of postmenopausal women, oral bisphosphonate use was associated with significantly lower lung cancer risk among never smokers, suggesting bisphosphonates may have a protective effect against lung cancer. Additional studies are needed to confirm our findings.

Published
2018

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

Author

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

Subjects
Male, Cancer Research, Epidemiology, pancreatic cancer, Alcohol, Gastroenterology, Cohort Studies, Alcohol Use and Health, chemistry.chemical_compound, pooled analysi, Prospective Studies, Cancer, Confounding, Substance Abuse, PanScan, Alcoholism, Oncology, Cohort, Public Health and Health Services, Female, Risk assessment, medicine.medical_specialty, Alcohol Drinking, Oncology and Carcinogenesis, pancreatic cancer cohort consortium, Article, Pooled analysis, Rare Diseases, Oral and Gastrointestinal, Clinical Research, Pancreatic cancer, Internal medicine, medicine, Humans, Aged, business.industry, Odds ratio, medicine.disease, Confidence interval, Surgery, Pancreatic Neoplasms, Good Health and Well Being, chemistry, Case-Control Studies, Digestive Diseases, business
Abstract

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

Published
2010
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9. Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types

Author

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

Published
2015
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10. Genome-wide Association Study Of Survival In Patients With Pancreatic Adenocarcinoma

Author

Kala Visvanathan, Jean Wactawski-Wende, Salvatore Panico, Andrea Z. LaCroix, Patricia Hartge, Charles S. Fuchs, Chen Wu, Mazda Jenab, Chengfeng Wang, Brian M. Wolpin, Poorva Mudgal, Anne Zeleniuch-Jacquotte, Kay-Tee Khaw, Laufey T. Amundadottir, Elio Riboli, Marie-Christine Boutron-Ruault, Edward Giovannucci, Wei Zheng, Federico Canzian, Guoliang Jiang, Emily Steplowski, Julie E. Buring, H. Bas Bueno-de-Mesquita, Myron D. Gross, Michelle Brotzman, Eric J. Jacobs, Joanne W. Elena, Demetrius Albanes, Eric J. Duell, Stephen J. Chanock, Dongxin Lin, Göran Hallmans, David J. Hunter, Charles Kooperberg, Geoffrey S. Tobias, Alan A. Arslan, Zhi Rong Qian, Guangwen Cao, Anne Tjønneland, Kathy J. Helzlsouer, Alpa V. Patel, Howard D. Sesso, Jarmo Virtamo, Rachael Z. Stolzenberg-Solomon, Robert N. Hoover, J. Michael Gaziano, Mousheng Xu, Hongbing Shen, Gloria M. Petersen, Kai Yu, Peter Kraft, Xiao-Ou Shu, Dimitrios Trichopoulos, Zhao-Shen Li, Julie B. Mendelsohn, Amy Hutchinson, Wu, C, Kraft, P, Stolzenberg Solomon, R, Steplowski, E, Brotzman, M, Xu, M, Mudgal, P, Amundadottir, L, Arslan, Aa, Bueno de Mesquita, Hb, Gross, M, Helzlsouer, K, Jacobs, Ej, Kooperberg, C, Petersen, Gm, Zheng, W, Albanes, D, Boutron Ruault, Mc, Buring, Je, Canzian, F, Cao, G, Duell, Ej, Elena, Jw, Gaziano, Jm, Giovannucci, El, Hallmans, G, Hutchinson, A, Hunter, Dj, Jenab, M, Jiang, G, Khaw, Kt, Lacroix, A, Li, Z, Mendelsohn, Jb, Panico, Salvatore, Patel, Av, Qian, Zr, Riboli, E, Sesso, H, Shen, H, Shu, Xo, Tjonneland, A, Tobias, G, Trichopoulos, D, Virtamo, J, Visvanathan, K, Wactawski Wende, J, Wang, C, Yu, K, Zeleniuch Jacquotte, A, Chanock, S, Hoover, R, Hartge, P, Fuchs, C, Lin, D, and Wolpin, Bm

Subjects
Oncology, Male, Genome-wide association study, Kaplan-Meier Estimate, Gastroenterology, 0302 clinical medicine, Models, 80 and over, 2.1 Biological and endogenous factors, Non-Receptor, Pancreas cancer, Cancer, Aged, 80 and over, 0303 health sciences, Principal Component Analysis, Molecular Epidemiology, Tumor, Single Nucleotide, Middle Aged, Protein Tyrosine Phosphatases, Non-Receptor, 3. Good health, Survival Rate, Europe, 030220 oncology & carcinogenesis, Adenocarcinoma, Female, Adult, Asian Continental Ancestry Group, medicine.medical_specialty, China, European Continental Ancestry Group, Clinical Sciences, and over, Biology, Genetic polymorphisms, Polymorphism, Single Nucleotide, White People, Article, Paediatrics and Reproductive Medicine, 03 medical and health sciences, Pancreatic Cancer, Rare Diseases, Asian People, Genetic, Internal medicine, Pancreatic cancer, Biomarkers, Tumor, medicine, Cancer Genetics, Genetics, Humans, In patient, Polymorphism, Càncer de pàncrees, 030304 developmental biology, Proportional Hazards Models, Aged, Models, Genetic, Molecular epidemiology, Gastroenterology & Hepatology, Prevention, Polimorfisme genètic, Human Genome, medicine.disease, Pancreatic Neoplasms, Cancer genetics, Protein Tyrosine Phosphatases, Digestive Diseases, Biomarkers, Follow-Up Studies, Genome-Wide Association Study
Abstract

Background and objective: Survival of patients with pancreatic adenocarcinoma is limited and few prognostic factors are known. We conducted a two-stage genome-wide association study (GWAS) to identify germline variants associated with survival in patients with pancreatic adenocarcinoma. Methods: We analysed overall survival in relation to single nucleotide polymorphisms (SNPs) among 1005 patients from two large GWAS datasets, PanScan I and ChinaPC. Cox proportional hazards regression was used in an additive genetic model with adjustment for age, sex, clinical stage and the top four principal components of population stratification. The first stage included 642 cases of European ancestry (PanScan), from which the top SNPs (p10(-5)) were advanced to a joint analysis with 363 additional patients from China (ChinaPC). Results: In the first stage of cases of European descent, the top-ranked loci were at chromosomes 11p15.4, 18p11.21 and 1p36.13, tagged by rs12362504 (p=1.63x10(-7)), rs981621 (p=1.65x10(-7)) and rs16861827 (p=3.75x10(-7)), respectively. 131 SNPs with p10(-5) were advanced to a joint analysis with cases from the ChinaPC study. In the joint analysis, the top-ranked SNP was rs10500715 (minor allele frequency, 0.37; p=1.72x10(-7)) on chromosome 11p15.4, which is intronic to the SET binding factor 2 (SBF2) gene. The HR (95% CI) for death was 0.74 (0.66 to 0.84) in PanScan I, 0.79 (0.65 to 0.97) in ChinaPC and 0.76 (0.68 to 0.84) in the joint analysis. Conclusions: Germline genetic variation in the SBF2 locus was associated with overall survival in patients with pancreatic adenocarcinoma of European and Asian ancestry. This association should be investigated in additional large patient cohorts.

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