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153. 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
Adult, Asian Continental Ancestry Group, Male, Lung Neoplasms, Lymphoma, European Continental Ancestry Group, Oncology and Carcinogenesis, Bone Neoplasms, Testicular Neoplasms, Neoplasms, Large B-Cell, Humans, Genetic Predisposition to Disease, Oncology & Carcinogenesis, Polymorphism, Chronic, Aged, Osteosarcoma, Leukemia, Smoking, B-Cell, Single Nucleotide, Middle Aged, Diffuse, Kidney Neoplasms, Lymphocytic, Urinary Bladder Neoplasms, Tissue Array Analysis, Female, Genome-Wide Association Study
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

154. 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

155. Characterization of large structural genetic mosaicism in human autosomes

Author

Machiela, Mitchell J, Zhou, Weiyin, Sampson, Joshua N, Dean, Michael C, Jacobs, Kevin B, Black, Amanda, Brinton, Louise A, Chang, I-Shou, Chen, Chu, Chen, Constance, Chen, Kexin, Cook, Linda S, Crous Bou, Marta, De Vivo, Immaculata, Doherty, Jennifer, Friedenreich, Christine M, Gaudet, Mia M, Haiman, Christopher A, Hankinson, Susan E, Hartge, Patricia, Henderson, Brian E, Hong, Yun-Chul, Hosgood, H Dean, Hsiung, Chao A, Hu, Wei, Hunter, David J, Jessop, Lea, Kim, Hee Nam, Kim, Yeul Hong, Kim, Young Tae, Klein, Robert, Kraft, Peter, Lan, Qing, Lin, Dongxin, Liu, Jianjun, Le Marchand, Loic, Liang, Xiaolin, Lissowska, Jolanta, Lu, Lingeng, Magliocco, Anthony M, Matsuo, Keitaro, Olson, Sara H, Orlow, Irene, Park, Jae Yong, Pooler, Loreall, Prescott, Jennifer, Rastogi, Radhai, Risch, Harvey A, Schumacher, Fredrick, Seow, Adeline, Setiawan, Veronica Wendy, Shen, Hongbing, Sheng, Xin, Shin, Min-Ho, Shu, Xiao-Ou, VanDen Berg, David, Wang, Jiu-Cun, Wentzensen, Nicolas, Wong, Maria Pik, Wu, Chen, Wu, Tangchun, Wu, Yi-Long, Xia, Lucy, Yang, Hannah P, Yang, Pan-Chyr, Zheng, Wei, Zhou, Baosen, Abnet, Christian C, Albanes, Demetrius, Aldrich, Melinda C, Amos, Christopher, Amundadottir, Laufey T, Berndt, Sonja I, Blot, William J, Bock, Cathryn H, Bracci, Paige M, Burdett, Laurie, Buring, Julie E, Butler, Mary A, Carreón, Tania, Chatterjee, Nilanjan, Chung, Charles C, Cook, Michael B, Cullen, Michael, Davis, Faith G, Ding, Ti, Duell, Eric J, Epstein, Caroline G, Fan, Jin-Hu, Figueroa, Jonine D, Fraumeni, Joseph F, Freedman, Neal D, Fuchs, Charles S, Gao, Yu-Tang, Gapstur, Susan M, Patiño-Garcia, Ana, Garcia-Closas, Montserrat, Gaziano, J Michael, Giles, Graham G, and Gillanders, Elizabeth M

Subjects
Chromosome Aberrations, Male, Genetics & Heredity, Medical And Health Sciences, Genome, Genotype, Mosaicism, Human Genome, Middle Aged, Biological Sciences, Clinical Research, Neoplasms, Genetics, 2.1 Biological and endogenous factors, Humans, Female, Aetiology, Human, Aged, Genome-Wide Association Study
Abstract

Analyses of genome-wide association study (GWAS) data have revealed that detectable genetic mosaicism involving large (>2 Mb) structural autosomal alterations occurs in a fraction of individuals. We present results for a set of 24,849 genotyped individuals (total GWAS set II [TGSII]) in whom 341 large autosomal abnormalities were observed in 168 (0.68%) individuals. Merging data from the new TGSII set with data from two prior reports (the Gene-Environment Association Studies and the total GWAS set I) generated a large dataset of 127,179 individuals; we then conducted a meta-analysis to investigate the patterns of detectable autosomal mosaicism (n = 1,315 events in 925 [0.73%] individuals). Restricting to events >2 Mb in size, we observed an increase in event frequency as event size decreased. The combined results underscore that the rate of detectable mosaicism increases with age (p value = 5.5 × 10(-31)) and is higher in men (p value = 0.002) but lower in participants of African ancestry (p value = 0.003). In a subset of 47 individuals from whom serial samples were collected up to 6 years apart, complex changes were noted over time and showed an overall increase in the proportion of mosaic cells as age increased. Our large combined sample allowed for a unique ability to characterize detectable genetic mosaicism involving large structural events and strengthens the emerging evidence of non-random erosion of the genome in the aging population.

Published
2015

156. 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

157. Mediterranean Diet and Telomere Length: A Systematic Review and Meta-Analysis

Author

Canudas, Silvia, Becerra-Tomás, Nerea, Hernández-Alonso, Pablo, Galié, Serena, Leung, Cindy, Crous-Bou, Marta, De Vivo, Immaculata, Gao, Yawen, Gu, Yian, Meinilä, Jelena, Milte, Catherine, García-Calzón, Sonia, Marti, Amelia, Boccardi, Virginia, Ventura-Marra, Melissa, and Salas-Salvadó, Jordi

Abstract

Accelerated telomere shortening has been associated with several age-related diseases and/or decreased lifespan in humans. The Mediterranean diet (MedDiet) is considered to be 1 of the most recognized diets for disease prevention and healthy aging, partially due to its demonstrated anti-inflammatory and antioxidative properties which may impact on telomere length (TL). The aim of this meta-analysis was to determine the associations between MedDiet adherence and TL maintenance. MEDLINE-PubMed and Cochrane databases were searched up to December 2018 for studies evaluating the association between MedDiet adherence and TL in blood cells. Two reviewers, working independently, screened all titles and abstracts to identify studies that met the inclusion criteria [cross-sectional, case-control, and prospective cohort studies and randomized clinical trials (RCTs) published in English and excluded nonoriginal articles]. Data were pooled by the generic inverse variance method using the random effects model and expressed as standardized mean difference (SMD). Heterogeneity was identified using the Cochran Q test and quantified by the I2statistic. A total of 8 original cross-sectional studies were included for the quantitative meta-analysis, comprising a total of 13,733 participants from 5 countries. A positive association between adherence to the MedDiet and TL was observed in all meta-analyses, with the exception of those conducted only in men: SMD (95% CI) of 0.130 (0.029; 0.231) for all subjects, 0.078 (0.005; 0.152) for women, and 0.095 (–0.005; 0.195) for men. Only 1 prospective cohort study and 1 RCT were identified, therefore, we could not undertake a meta-analysis for these study designs. The present meta-analysis of cross-sectional studies demonstrates that higher MedDiet adherence is associated with longer TL. At the same time, larger and high-quality prospective studies and clinical trials are warranted to confirm this association.

Published
2020
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158. Dietary intake of plant- and animal-derived protein and incident cardiovascular diseases: the pan-European EPIC-CVD case-cohort study

Author

Zheng, Ju-Sheng, Steur, Marinka, Imamura, Fumiaki, Freisling, Heinz, Johnson, Laura, van der Schouw, Yvonne T., Tong, Tammy Y.N., Weiderpass, Elisabete, Bajracharya, Rashmita, Crous-Bou, Marta, Dahm, Christina C., Heath, Alicia K., Ibsen, Daniel B., Jannasch, Franziska, Katzke, Verena, Masala, Giovanna, Moreno-Iribas, Conchi, Sacerdote, Carlotta, Schulze, Matthias B., Sieri, Sabina, Wareham, Nicholas J., Danesh, John, Butterworth, Adam S., and Forouhi, Nita G.

Abstract

Epidemiological evidence suggests that a potential association between dietary protein intake and cardiovascular disease (CVD) may depend on the protein source, i.e. plant- or animal- derived, but past research was limited and inconclusive.

Published
2024
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159. 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, Dagnall, Casey, Hautman, Christopher, Jacobs, Kevin B, Abnet, Christian C, Aldrich, Melinda C, Amos, Christopher, 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 A, 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, Garcia-Closas, Montserrat, Gaudet, Mia M, Gaziano, J Michael, Giles, Graham G, Gillanders, Elizabeth M, Giovannucci, Edward L, Goldin, Lynn, Goldstein, Alisa M, Haiman, Christopher A, Hallmans, Göran, Hankinson, Susan E, Harris, Curtis C, Henriksson, Roger, Holly, Elizabeth A, Hong, Yun-Chul, Hoover, Robert N, Hsiung, Chao A, Hu, Nan, Hu, 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, Koh, Woon-Puay, Kolonel, Laurence N, Kooperberg, Charles, Kraft, Peter, Krogh, Vittorio, Kurtz, Robert C, LaCroix, Andrea, 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, Nuria, Matsuo, Keitaro, McNeill, Lorna H, McWilliams, Robert R, Melin, Beatrice S, Mirabello, Lisa, Moore, Lee, Olson, Sara H, Orlow, Irene, Park, Jae Yong, Patiño-Garcia, Ana, Peplonska, Beata, Peters, Ulrike, Petersen, Gloria M, Pooler, Loreall, Prescott, Jennifer, Prokunina-Olsson, Ludmila, Purdue, Mark P, Qiao, You-Lin, Rajaraman, Preetha, Real, Francisco X, Riboli, Elio, Risch, Harvey A, Rodriguez-Santiago, Benjamin, 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, 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, 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, Dagnall, Casey, Hautman, Christopher, Jacobs, Kevin B, Abnet, Christian C, Aldrich, Melinda C, Amos, Christopher, 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 A, 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, Garcia-Closas, Montserrat, Gaudet, Mia M, Gaziano, J Michael, Giles, Graham G, Gillanders, Elizabeth M, Giovannucci, Edward L, Goldin, Lynn, Goldstein, Alisa M, Haiman, Christopher A, Hallmans, Göran, Hankinson, Susan E, Harris, Curtis C, Henriksson, Roger, Holly, Elizabeth A, Hong, Yun-Chul, Hoover, Robert N, Hsiung, Chao A, Hu, Nan, Hu, 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, Koh, Woon-Puay, Kolonel, Laurence N, Kooperberg, Charles, Kraft, Peter, Krogh, Vittorio, Kurtz, Robert C, LaCroix, Andrea, 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, Nuria, Matsuo, Keitaro, McNeill, Lorna H, McWilliams, Robert R, Melin, Beatrice S, Mirabello, Lisa, Moore, Lee, Olson, Sara H, Orlow, Irene, Park, Jae Yong, Patiño-Garcia, Ana, Peplonska, Beata, Peters, Ulrike, Petersen, Gloria M, Pooler, Loreall, Prescott, Jennifer, Prokunina-Olsson, Ludmila, Purdue, Mark P, Qiao, You-Lin, Rajaraman, Preetha, Real, Francisco X, Riboli, Elio, Risch, Harvey A, Rodriguez-Santiago, Benjamin, 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, 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, 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
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170. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

Author

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

Published
2016
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172. 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

173. 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

174. Amyloid‐positive individuals with subjective cognitive decline present increased CSF neurofilament light levels that relate to hippocampal volume: Neuropsychiatry and behavioral neurology: The neuropsychiatry of subjective cognitive disorder...

Author

Sánchez‐Benavides, Gonzalo, Suárez‐Calvet, Marc, Milà‐Alomà, Marta, Arenaza‐Urquijo, Eider M., Grau‐Rivera, Oriol, Operto, Greg, Gispert, Juan Domingo, Vilor‐Tejedor, Natalia, Sala‐Vila, Aleix, Crous‐Bou, Marta, González‐de‐Echávarri, José Maria, Minguillón, Carolina, Fauria, Karine, Simon, Maryline, Kollmorgen, Gwendlyn, Zetterberg, Henrik, Blennow, Kaj, and Molinuevo, Jose Luis

Abstract

Background: Neurofilament light chain (NfL) is a biomarker of neurodegeneration. While cerebrospinal (CSF) NfL is increased in individuals with AD dementia as compared to controls and mild cognitive impairment, studies in cognitively unimpaired individuals with subjective cognitive decline (SCD) are scarce. SCD may represent the first clinical symptom of AD. We aimed at investigating the association between presence of SCD and CSF NfL levels, the interaction between SCD and amyloid‐β (Aβ) status on NfL, and their relationship to hippocampal volume. Method: We analyzed 78 SCD and 200 controls from the Alfa+ cohort [mean age 61(4.6)] with Roche NeuroToolKit. We defined SCD as a positive answer to the question "Do you perceive memory or cognitive difficulties?" from the SCD‐Questionnaire. We assessed vascular risk factors and mood with the CAIDE score and the Hospital Anxiety and Depression Scale (HADS), respectively, and calculated hippocampal volumes using FreeSurfer V6.0. ANCOVA models accounting for covariates (age, gender, and HADS) were used to test the association between log10(NfL) levels and SCD status, and between log10(NfL) and bilateral total intracranial volume (TIV)‐adjusted hippocampal volume. The interactions SCD*Aβ42/Aβ40 and SCD*hippocampal*dichotomized amyloid status [Aβ+ (n=88) vs Aβ‐ (n=190), defined by the cut‐off of 0.071 for Aβ42/Aβ40] were also tested, and within group analysis performed when interactions were significant. Result: SCD subjects displayed higher NfL (p=0.002, Partial Eta2=0.033) and lower Aβ42/Aβ40 (p=0.044, Partial Eta2 =0.015) than controls, after adjusting by age, gender and HADS (Table 1, Figure 1). Adding the cardiovascular risk factor score CAIDE as a covariate did not change these associations. We observed a significant SCD*Aβ42/Aβ40 interaction (p=0.028) on NfL. A sensitivity analysis stratifying for Aβ‐status showed that the association between SCD and NfL was significant only in Aβ+ individuals (p=0.006, A‐ p=0.21) (Figure 2). Further, the association between hippocampal volume and NfL was only significant in the Aβ+ individuals with SCD (p=0.04, age‐adjusted r=0.38, n=30) (Figure 3). Conclusion: Aβ+ individuals with SCD displayed increased levels of CSF‐NfL. This association was independent of age, gender, anxiety/depression and vascular risk, and was related to hippocampal atrophy. The presence of SCD in Aβ+ may represent an early symptom related with neurodegeneration. [ABSTRACT FROM AUTHOR]

Published
2020
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175. Weight loss predicts Alzheimer's disease biomarker positivity in cognitively unimpaired middle‐aged adults: Epidemiology: Cardiovascular risk factors.

Author

Grau‐Rivera, Oriol, Navalpotro, Irene, Sánchez‐Benavides, Gonzalo, Suárez‐Calvet, Marc, Milà‐Alomà, Marta, Arenaza‐Urquijo, Eider M, Salvadó, Gemma, Sala‐Vila, Aleix, Crous‐Bou, Marta, González‐de‐Echávarri, José Maria, Minguillón, Carolina, Farrar, Gill, Buckley, Chris J, Niñerola‐Baizán, Aida, Perissinotti, Andrés, Simon, Maryline, Kollmorgen, Gwendlyn, Eichenlaub, Udo, Zetterberg, Henrik, and Blennow, Kaj

Abstract

Background: Weight loss is common in Alzheimer's disease (AD) and may start before cognitive impairment, but little is known about the relationship between weight change and AD biomarkers in the preclinical Alzheimer's continuum. We aimed to assess the association between weight change and AD biomarkers and cognitive performance in cognitively unimpaired (CU) adults from the ALFA+ study. Method: We analyzed data from 295 CU middle‐aged adults with two consecutive (mean interval 3.7 years) weight measures and neuropsychological assessments (n=267). Preclinical Alzheimer's Cognitive Composite (PACC) was computed as an average of z‐scores of episodic memory, semantic fluency and processing speed measures. We measured cerebrospinal fluid (CSF) levels of Aβ42, Aβ40, p‐tau, t‐tau, neurofilament light (NfL) and neurogranin using the Roche NeuroToolKit and Elecsys® immunoassays (n=280), and performed a [18F]flutemetamol PET scan in the follow‐up visit (n=252). PET results were dichotomized (Aβ positive or negative) based on visual read. Using established CSF cutoffs, we grouped participants in three biomarker categories: A‐T‐ (both Aβ and tau negative), A+T‐ (Aβ positive only) and A+T+ (both Aβ and tau positive). Linear and logistic regression and Kernel‐weighted local polynomial smoothing were used for analyses, which were adjusted by age, sex, body mass index, APOE genotype and years of education, as appropriate. Result: Weight loss predicted amyloid PET positivity (odds ratio 1.1, p=0.028) and was associated with significantly higher CSF levels of p‐tau (p=0.005), t‐tau (p=0.005) and neurogranin (p=0.002) (Table 1). Weight loss ≥5% (a standard cutoff for clinically relevant weight change) yielded 87% specificity and 30% sensitivity for amyloid PET positivity. Participants from the A+T+ group experienced significantly higher weight loss compared to A+T‐ (p=0.0029) and A‐T‐ (p=0.0005) groups (Figure 1). Weight loss was not associated with longitudinal changes in cognitive performance and preceded cognitive decline when using Aβ42/40 as a proxy of AD change progression (Table 1, Figure 2). Conclusion: Weight loss predicts amyloid PET positivity in CU middle‐aged adults. Our results suggest that weight loss is mainly related with changes in tau‐related and synaptic dysfunction biomarkers and may precede cognitive decline in the preclinical stage of the Alzheimer's continuum. [ABSTRACT FROM AUTHOR]

Published
2020
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176. Air pollution and biomarkers of Alzheimer's disease in cognitively unimpaired individuals: Epidemiology: Effects of air pollution on cognition.

Author

Crous‐Bou, Marta, Alemany, Silvia, Vilor‐Tejedor, Natalia, Milà‐Alomà, Marta, Suárez‐Calvet, Marc, Salvadó, Gemma, Cirach, Marta, Arenaza‐Urquijo, Eider M, Sánchez‐Benavides, Gonzalo, Grau‐Rivera, Oriol, Minguillón, Carolina, Fauria, Karine, Gispert, Juan Domingo, Nieuwenhuijsen, Mark, Zetterberg, Henrik, Blennow, Kaj, Kollmorgen, Gwendlyn, Eichenlaub, Udo, Sunyer, Jordi, and Molinuevo, Jose Luis

Abstract

Background: Air quality might contribute to incidence of dementia‐related disorders, including Alzheimer's disease (AD). The aim of our study was to examine whether air pollution may be associated with abnormal concentrations of AD cerebrospinal fluid (CSF) and neuroimaging biomarkers in cognitively unimpaired individuals at increased risk of AD. Additionally, potential effect modification by amyloid‐β(Aβ) and APOE‐ɛ4 status was investigated. Methods: The ALFA (ALzheimer and FAmilies) study is a prospective cohort of cognitively unimpaired, middle‐aged subjects, many AD patients' offspring. Land Use Regression models were used to estimate residential exposure to air pollutants including nitrogen oxides (NO2, NOx) and particulate matter (PM2.5, PM2.5 abs, PM10, PM coarse). For a subset, we measured CSF levels of Aβ42, Aβ40, p‐tau, t‐tau and neurofilament light (NfL) using NeuroToolKit and Elecsys® immunoassays (Roche Diagnostics). They also underwent a [18F]flutemetamol amyloid PET scan to assess cerebral amyloid load (Centiloid). A total of 148 participants (all residents of Barcelona) with data available on exposure to air pollutants and core AD biomarkers were included in this cross‐sectional analysis. Multiple linear regression models were used to test the association between exposure to air pollutants and biomarkers. Age, sex, years of education and APOE‐ɛ4 status were included as potential confounders. To test for effect modification, Aβ positivity was defined by an Aβ42/Aβ40 ratio<0.071. Stratified analyses by APOE genotype were also performed. Results: Greater exposure to air pollutants was associated with increased levels of CSF p‐tau, t‐tau and NfL, and reduced Aβ42/40 ratio. Additionally, higher exposure to nitrogen oxides was significantly associated with increased Aβ deposition in the brain (Figure1;*p<0.05). Such associations were driven by Aβ‐negative individuals (p‐interaction<0.05) (Figure 2;*p<0.05). Furthermore, the association between increased exposure to air pollutants and Ab deposition was only seen in APOE‐ɛ4 non‐carriers, while the positive association between exposure to air pollutants and CSF p‐tau, t‐tau and NfL was only observed among APOE‐ɛ4 carriers (Figure 3;*p<0.05). Conclusion: In a population of cognitively unimpaired adults with increased risk of AD, exposure to air pollution is associated with abnormal core AD biomarker results. Further research is granted to elucidate the mechanisms involved in such associations. [ABSTRACT FROM AUTHOR]

Published
2020
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177. The effect of physical activity on CSF biomarkers of Alzheimer's disease differs between men and women: Biomarkers (non‐neuroimaging): Alzheimer's disease incidence, risk factors and biomarkers.

Author

Milà‐Alomà, Marta, Salvadó, Gemma, Gispert, Juan Domingo, Vilor‐Tejedor, Natalia, Grau‐Rivera, Oriol, Sala‐Vila, Aleix, Sanchez‐Benavides, Gonzalo, Arenaza‐Urquijo, Eider M, Crous‐Bou, Marta, González‐de‐Echávarri, José Maria, Minguillón, Carolina, Fauria, Karine, Simon, Maryline, Kollmorgen, Gwendlyn, Rodríguez‐Lantero, Juan, Ashton, Nicholas J, Zetterberg, Henrik, Blennow, Kaj, Molinuevo, Jose Luis, and Suárez‐Calvet, Marc

Abstract

Background: Increasing evidence suggests that sex influences several aspects of Alzheimer's disease (AD). Cardiovascular risk factors are associated with AD, and men and women differ in the prevalence of these risk factors. We aimed at determining whether (1) sex and cardiovascular risk factors have an effect on CSF biomarkers; (2) sex modifies the association between cardiovascular risk factors and CSF biomarkers in middle aged cognitively unimpaired individuals of the ALFA+ study. Method: We measured CSF Ab42, Ab40, p‐tau, t‐tau, neurofilament light (NfL), neurogranin, sTREM2, YKL40, GFAP, S100, IL6, sVCAM1, sICAM1, MCP1 and α‐synuclein in 381 participants of the ALFA+ study (34.4% Ab‐positive, 65.6% Ab‐negative; Ab42/40 cutoff = 0.071). Biomarker measurements were performed using MSD, Roche NeuroToolKit and Elecsys® immunoassays. The following cardiovascular risk variables were studied: hypertension, smoking, dyslipidaemia, physical activity, LDL and HDL cholesterol, glucose, Hb1Ac, triglycerides, BMI and systolic and diastolic blood pressure. ANCOVA was performed to test the effect of sex on each biomarker and potential interaction effects between sex and cardiovascular variables. Result: We found that CSF NfL, GFAP, IL6, sVCAM1 and MCP1 were higher in men, while CSF neurogranin and YKL40 were higher in women. These differences were still significant after adjusting for Ab pathology. Regarding cardiovascular variables, men had higher diastolic blood pressure, glucose and triglycerides, while women had higher total, LDL and HDL cholesterol. After adjusting for these cardiovascular variables, sex differences in CSF NfL were still significant, suggesting that they were not confounded by cardiovascular factors (Table 1). In the whole cohort, we observed that sex modifies the association with physical activity levels and CSF NfL (interaction 'sex x physical activity': p=0.019). After stratifying by Ab status, we observed that higher physical activity was associated with lower CSF NfL only in Ab positive men (Figure 1). Conclusion: Sex affects CSF biomarkers and modifies their association with cardiovascular risk factors. Specifically, physical activity is associated with lower NfL in middle aged men in the preclinical stage of the Alzheimer's continuum, but not in women. Our results suggest that the impact of cardiovascular risk factors on neurodegeneration differs between men and women. [ABSTRACT FROM AUTHOR]

Published
2020
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178. Genetically predicted telomere length and Alzheimer's disease endophenotypes: A Mendelian randomization study: Epidemiology / Innovative methods in epidemiology (i.e., assessment methods, design, recruitment strategies, statistical methods, etc.).

Author

Vilor‐Tejedor, Natalia, Rodríguez‐Fernández, Blanca, Milà‐Alomà, Marta, Arenaza‐Urquijo, Eider M, Suárez‐Calvet, Marc, Sanchez‐Benavides, Gonzalo, Grau‐Rivera, Oriol, Minguillón, Carolina, Fauria, Karine, Zetterberg, Henrik, Blennow, Kaj, Kollmorgen, Gwendlyn, Eichenlaub, Udo, Gispert, Juan Domingo, DeVivo, Immaculata, Sala‐Vila, Aleix, Molinuevo, Jose Luis, and Crous‐Bou, Marta

Abstract

Background: Telomere length (TL) is a putative biomarker of biological aging and aging‐related outcomes. Observational studies are limited to conclude whether TL is causally associated with AD or a marker of an underlying pathological process. Mendelian randomization (MR) was developed for assessing causality using genetic variants in epidemiological research. Our main objective was to test the potential causal role of TL in cognitive performance, brain vulnerability and AD core biomarkers through an MR analysis. Methods: Our analysis was conducted in the context of the ALFA (ALzheimer and FAmilies) study. We created episodic memory, executive function and global cognitive composites. We calculated an AD signature as a composite measure reflecting cortical thickness of specific AD vulnerable regions. We measured cerebrospinal fluid (CSF) levels of amyloid‐β(Aβ)42, Aβ40, p‐tau, t‐tau and neurofilament light (NfL) using NeuroToolKit and Elecsys® immunoassays (Roche Diagnostics). Genome‐wide genotyping was performed. MR analyses using 3 Single Nucleotide Polymorphisms (SNPs) (rs2736100, rs9420907, rs755017) associated with TL identified in Genome‐wide Association studies (GWAS) were used as instrumental variables to determine the predicted effect of TL on AD endophenotypes: cognitive performance, AD signature, and AD biomarkers. Causal effects of TL were estimated using the inverse‐variance weighted method. Stratified analyses by APOE‐ɛ4 status were conducted. Results: MR analysis revealed a significant association between SNPs predicting shorter TL and increased levels of NfL, supporting a potential causal role of TL on biomarkers of neuronal injury (Table 1; Figure 1). Additionally, we observed suggestive evidence of causality between shorter TL and worse episodic memory, and reduced cortical thickness in the AD signature (Table 1). Effect modification by APOE‐ɛ4 genotype was also suggested: associations between SNPs predicting short TL and worse cognitive performance, reduced thickness in the AD signature, and increased levels of NfL were only observed among APOE‐ɛ4 non‐carriers (Table 2). Conclusions: Preliminary results of our MR analysis showed an association between SNPs predicting shorter TL and AD endophenotypes, suggesting a potential causal role of telomeres in AD vulnerability, specifically in individuals not at increased genetic risk of AD. Further observational and genetic analyses in larger datasets are warranted to better understand these associations. [ABSTRACT FROM AUTHOR]

Published
2020
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179. Amyloid‐β, tau, synaptic dysfunction, neurodegeneration, glial and vascular biomarkers in the preclinical stage of the Alzheimer's continuum: Biomarkers (non‐neuroimaging) / novel biomarkers.

Author

Suárez‐Calvet, Marc, Milà‐Alomà, Marta, Salvadó, Gemma, Gispert, Juan Domingo, Vilor‐Tejedor, Natalia, Grau‐Rivera, Oriol, Sala‐Vila, Aleix, Sanchez‐Benavides, Gonzalo, Arenaza‐Urquijo, Eider M, Crous‐Bou, Marta, González‐de‐Echávarri, José Maria, Minguillón, Carolina, Fauria, Karine, Simon, Maryline, Kollmorgen, Gwen, Rodríguez‐Lantero, Juan, Ashton, Nicholas J, Zetterberg, Henrik, Blennow, Kaj, and Molinuevo, Jose Luis

Abstract

Background: Alzheimer's disease (AD) comprises a preclinical stage characterized by pathophysiological changes that occur decades before symptoms arise. Despite the importance of this stage, the biological pathways involved are not yet well understood. The main aim of this study is to define the pathophysiological processes, as measured by CSF biomarkers changes, that occur in the preclinical stage of the Alzheimer's continuum in a finely‐characterized cohort of cognitively unimpaired individuals. Methods: We measured a comprehensive set of CSF biomarkers that reflect different pathophysiological processes in 381 cognitively unimpaired participants aged between 49 and 73 years of the ALFA+ study (61% women; 53% APOE‐ε4 carriers; 34% Aβ positive). Specifically, we measured CSF biomarkers related to amyloid‐β (Aβ42, Aβ40) or tau (p‐tau, t‐tau) metabolism, neuronal and axonal damage (NfL), synaptic dysfunction (neurogranin), neuroinflammation (IL6, MCP1), micro‐ and astroglial markers (sTREM2, YKL40, GFAP, S100), vascular injury (sVCAM1, sICAM1), and total α‐synuclein. Measurements were performed using MSD, NeuroToolKit and Elecsys® immunoassays. Results: We found that CSF tau‐related (p‐tau and t‐tau) and synaptic dysfunction (neurogranin) biomarkers increase throughout ageing only in Aβ‐positive individuals. In contrast, neuronal injury (NfL), micro‐ and astroglial (sTREM2, YKL40, GFAP) and vascular (sVCAM1, sICAM1) CSF biomarkers increase with ageing both in Aβ‐positive and ‐negative individuals (Fig.1). We modelled the changes in CSF biomarkers as a function of CSF Aβ42/40 ratio, p‐tau and p‐tau/Aβ42, which were used as proxies of disease progression. We observed that the first change that occurs in the Alzheimer's continuum is a decrease in the Aβ42/40 ratio. Shortly after this ratio becomes positive, there is a steep increase in CSF p‐tau, t‐tau, neurogranin and, to lesser extent, in CSF NfL and glial biomarkers (Fig. 2). Conclusion: Our results show that multiple biological pathways are altered very early in the Alzheimer's continuum, but differ in their association with Aβ pathology. Whereas CSF tau‐related and synaptic dysfunction biomarkers change promptly and specifically when there is underlying Aβ pathology, CSF NfL and glial biomarkers have a less pronounced and specific increase. Altogether, our results suggest that different biological pathways could be targeted during the preclinical stage of the Alzheimer's continuum. [ABSTRACT FROM AUTHOR]

Published
2020
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180. Episodic memory and executive functions in cognitively healthy individuals display distinct neuroanatomical correlates which are differentially modulated by aging.

Author

Cacciaglia, Raffaele, Molinuevo, José Luis, Sánchez‐Benavides, Gonzalo, Falcón, Carles, Gramunt, Nina, Brugulat‐Serrat, Anna, Grau, Oriol, Gispert, Juan Domingo, Camí, Jordi, Fauria, Karine, Suárez‐Calvet, Marc, Minguillón, Carolina, Salvadó, Gemma, Operto, Gregory, Crous‐Bou, Marta, Polo, Albina, Mustata, Cristina, Tenas, Laia, Marne, Paula, and Gotsens, Xavi

Abstract

The neuroanatomical bases of episodic memory (EM) and executive functions (EFs) have been widely addressed in patients with brain damage and in individuals with neurologic disorders. These studies reported that larger brain structures support better outcomes in both cognitive domains, thereby supporting the "bigger is better" account. However, relatively few studies have explored the cerebral morphological properties underlying EM and EFs in cognitively healthy individuals and current findings indicate no unitary theoretical explanation for the structure–function relationship. Moreover, existing studies have typically restricted the analyses to a priori defined regions of interest. Here we conducted unbiased voxel‐wise analysis of the associations between regional gray as well as white matter volumes (GMv; WMv) and performance in both cognitive domains in a sample of 463 cognitively intact individuals. We found that efficiency in EM was predicted by lower GMv in brain areas belonging to the default‐mode network (DMN). By contrast, EFs performance was predicted by larger GMv in a distributed set of regions, which overlapped with the executive control network (ECN). Volume of white matter bundles supporting both cross‐cortical and interhemispheric connections was positively related to processing speed. Furthermore, aging modulated the relationship between regional volumes and cognitive performance in several areas including the hippocampus and frontal cortex. Our data extend the critical role of the DMN and ECN by showing that variability in their morphological properties, and not only their activation patterns, affects EM and EFs, respectively. Moreover, our finding that aging reverts these associations supports previously advanced theories of cognitive neurodevelopment. [ABSTRACT FROM AUTHOR]

Published
2018
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181. Relation of long-term patterns in caregiving activity and depressive symptoms to telomere length in older women.

Author

Chang, Shun-Chiao, Crous-Bou, Marta, Prescott, Jennifer, Rosner, Bernard, Simon, Naomi M., Wang, Wei, De Vivo, Immaculata, and Okereke, Olivia I.

Subjects
*MENTAL health of older women, *MENTAL depression, *TELOMERES, *SYMPTOMS, *STRESS in old age
Abstract

Background Research links psychological stress to accelerated cellular aging. Here we examined whether long-term patterns of depression and caregiving burden, forms of chronic psychological stress, were associated with shorter telomere length, a biomarker of cellular aging. Methods The study included 1250 healthy older women (mean: 68.0; range: 60–81 years) in the Nurses’ Health Study. Long-term patterns in depressive symptoms and caregiving activity (separated into care of children/grandchildren vs. ill or disabled family members/others) incorporated questionnaire data between 1992 and 2000; relative leukocyte telomere lengths (LTLs) were measured in 2000–2001. Least-squares means LTL z-scores were calculated across categories of depression patterns and caregiving intensity. Results Six empirically-derived latent classes of depressive symptom trajectories were identified: minimal-stable (63.7%), mild-worsening (3.9%), subthreshold-improving (22.8%), subthreshold-worsening (2.7%), clinical range depressive-improving (6.2%), and clinical range depressive-persistent (0.6%). After collapsing trajectory patterns into 4 groups (combining those with minimal and mild symptoms into one group and those with clinical range depressive symptoms into one group) due to very small sample sizes in some groups, we observed marginal associations ( p  = 0.07): e.g., the least-squares means LTL z-scores were lowest (−0.08; 95% CI: −0.22 to 0.06) for the clinical range depressive symptoms group and highest (0.12; 0.04–0.20) for the subthreshold-improving group (Tukey’s post-hoc pairwise p  = 0.07). With six depressive symptom trajectories, no significant associations were observed with regard to telomere lengths. There were no significant associations between caregiving intensity and LTLs. Conclusions There were no associations between long-term patterns of caregiving burden and telomere lengths among older women. Possible differences in telomere lengths by types of long-term depressive symptom trajectories may warrant further investigation. [ABSTRACT FROM AUTHOR]

Published
2018
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182. Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for Thirteen Cancer Types

Author

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

Published
2015
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183. Characterization of Large Structural Genetic Mosaicism in Human Autosomes

Author

Machiela, Mitchell J., primary, Zhou, Weiyin, additional, Sampson, Joshua N., additional, Dean, Michael C., additional, Jacobs, Kevin B., additional, Black, Amanda, additional, Brinton, Louise A., additional, Chang, I-Shou, additional, Chen, Chu, additional, Chen, Constance, additional, Chen, Kexin, additional, Cook, Linda S., additional, Crous Bou, Marta, additional, De Vivo, Immaculata, additional, Doherty, Jennifer, additional, Friedenreich, Christine M., additional, Gaudet, Mia M., additional, Haiman, Christopher A., additional, Hankinson, Susan E., additional, Hartge, Patricia, additional, Henderson, Brian E., additional, Hong, Yun-Chul, additional, Hosgood, H. Dean, additional, Hsiung, Chao A., additional, Hu, Wei, additional, Hunter, David J., additional, Jessop, Lea, additional, Kim, Hee Nam, additional, Kim, Yeul Hong, additional, Kim, Young Tae, additional, Klein, Robert, additional, Kraft, Peter, additional, Lan, Qing, additional, Lin, Dongxin, additional, Liu, Jianjun, additional, Le Marchand, Loic, additional, Liang, Xiaolin, additional, Lissowska, Jolanta, additional, Lu, Lingeng, additional, Magliocco, Anthony M., additional, Matsuo, Keitaro, additional, Olson, Sara H., additional, Orlow, Irene, additional, Park, Jae Yong, additional, Pooler, Loreall, additional, Prescott, Jennifer, additional, Rastogi, Radhai, additional, Risch, Harvey A., additional, Schumacher, Fredrick, additional, Seow, Adeline, additional, Setiawan, Veronica Wendy, additional, Shen, Hongbing, additional, Sheng, Xin, additional, Shin, Min-Ho, additional, Shu, Xiao-Ou, additional, VanDen Berg, David, additional, Wang, Jiu-Cun, additional, Wentzensen, Nicolas, additional, Wong, Maria Pik, additional, Wu, Chen, additional, Wu, Tangchun, additional, Wu, Yi-Long, additional, Xia, Lucy, additional, Yang, Hannah P., additional, Yang, Pan-Chyr, additional, Zheng, Wei, additional, Zhou, Baosen, additional, Abnet, Christian C., additional, Albanes, Demetrius, additional, Aldrich, Melinda C., additional, Amos, Christopher, additional, Amundadottir, Laufey T., additional, Berndt, Sonja I., additional, Blot, William J., additional, Bock, Cathryn H., additional, Bracci, Paige M., additional, Burdett, Laurie, additional, Buring, Julie E., additional, Butler, Mary A., additional, Carreón, Tania, additional, Chatterjee, Nilanjan, additional, Chung, Charles C., additional, Cook, Michael B., additional, Cullen, Michael, additional, Davis, Faith G., additional, Ding, Ti, additional, Duell, Eric J., additional, Epstein, Caroline G., additional, Fan, Jin-Hu, additional, Figueroa, Jonine D., additional, Fraumeni, Joseph F., additional, Freedman, Neal D., additional, Fuchs, Charles S., additional, Gao, Yu-Tang, additional, Gapstur, Susan M., additional, Patiño-Garcia, Ana, additional, Garcia-Closas, Montserrat, additional, Gaziano, J. Michael, additional, Giles, Graham G., additional, Gillanders, Elizabeth M., additional, Giovannucci, Edward L., additional, Goldin, Lynn, additional, Goldstein, Alisa M., additional, Greene, Mark H., additional, Hallmans, Goran, additional, Harris, Curtis C., additional, Henriksson, Roger, additional, Holly, Elizabeth A., additional, Hoover, Robert N., additional, Hu, Nan, additional, Hutchinson, Amy, additional, Jenab, Mazda, additional, Johansen, Christoffer, additional, Khaw, Kay-Tee, additional, Koh, Woon-Puay, additional, Kolonel, Laurence N., additional, Kooperberg, Charles, additional, Krogh, Vittorio, additional, Kurtz, Robert C., additional, LaCroix, Andrea, additional, Landgren, Annelie, additional, Landi, Maria Teresa, additional, Li, Donghui, additional, Liao, Linda M., additional, Malats, Nuria, additional, McGlynn, Katherine A., additional, McNeill, Lorna H., additional, McWilliams, Robert R., additional, Melin, Beatrice S., additional, Mirabello, Lisa, additional, Peplonska, Beata, additional, Peters, Ulrike, additional, Petersen, Gloria M., additional, Prokunina-Olsson, Ludmila, additional, Purdue, Mark, additional, Qiao, You-Lin, additional, Rabe, Kari G., additional, Rajaraman, Preetha, additional, Real, Francisco X., additional, Riboli, Elio, additional, Rodríguez-Santiago, Benjamín, additional, Rothman, Nathaniel, additional, Ruder, Avima M., additional, Savage, Sharon A., additional, Schwartz, Ann G., additional, Schwartz, Kendra L., additional, Sesso, Howard D., additional, Severi, Gianluca, additional, Silverman, Debra T., additional, Spitz, Margaret R., additional, Stevens, Victoria L., additional, Stolzenberg-Solomon, Rachael, additional, Stram, Daniel, additional, Tang, Ze-Zhong, additional, Taylor, Philip R., additional, Teras, Lauren R., additional, Tobias, Geoffrey S., additional, Viswanathan, Kala, additional, Wacholder, Sholom, additional, Wang, Zhaoming, additional, Weinstein, Stephanie J., additional, Wheeler, William, additional, White, Emily, additional, Wiencke, John K., additional, Wolpin, Brian M., additional, Wu, Xifeng, additional, Wunder, Jay S., additional, Yu, Kai, additional, Zanetti, Krista A., additional, Zeleniuch-Jacquotte, Anne, additional, Ziegler, Regina G., additional, de Andrade, Mariza, additional, Barnes, Kathleen C., additional, Beaty, Terri H., additional, Bierut, Laura J., additional, Desch, Karl C., additional, Doheny, Kimberly F., additional, Feenstra, Bjarke, additional, Ginsburg, David, additional, Heit, John A., additional, Kang, Jae H., additional, Laurie, Cecilia A., additional, Li, Jun Z., additional, Lowe, William L., additional, Marazita, Mary L., additional, Melbye, Mads, additional, Mirel, Daniel B., additional, Murray, Jeffrey C., additional, Nelson, Sarah C., additional, Pasquale, Louis R., additional, Rice, Kenneth, additional, Wiggs, Janey L., additional, Wise, Anastasia, additional, Tucker, Margaret, additional, Pérez-Jurado, Luis A., additional, Laurie, Cathy C., additional, Caporaso, Neil E., additional, Yeager, Meredith, additional, and Chanock, Stephen J., additional

Published
2015
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184. Influències clíniques i ambientals en la prevalença de mutacions en l'oncogèn K-ras en pacients amb adenocarcinoma ductal de pàncrees

Author

Crous Bou, Marta, Porta Serra, Miquel, and Universitat Autònoma de Barcelona. Departament de Pediatria, d'Obstetrícia i Ginecologia i de Medicina Preventiva

Subjects
Oncogens, Epidemiologia, Ciències de la Salut, Càncer de pàncrees
Abstract

Antecedents La prevenció primària de l'adenocarcinoma ductal de pàncrees (ADP) està limitada per la falta de coneixement sobre la seva etiologia. El factor de risc més ben establert és el consum de tabac, però explica només una petita proporció de casos. Es discuteix el paper d'altres factors etiològics com els antecedents patològics de diabetis i pancreatitis, la dieta, determinades exposicions ambientals o laborals, i els factors hereditaris. Mutacions puntuals en l'oncogèn K-ras, i la seva conseqüent activació, són presents en més del 80% dels casos d'ADP; és un dels esdeveniments genètics fonamentals perquè el càncer tingui lloc. L'activació d'aquest oncogèn dóna lloc a gran varietat de respostes, des de l'augment de la proliferació cel·lular fins a la inhibició de l'apoptosi, en funció del context cel·lular. Els gens Ras són dianes crítiques per als carcinògens químics; els càncers de pàncrees amb i sense mutacions en l'oncogèn K-ras probablement es desenvolupen a partir de diferents interaccions gen-ambient. Tot i això, els estils de vida i les exposicions ambientals que poden influir en la presència de mutacions en el gen K-ras són pràcticament desconeguts. L'objectiu general d'aquesta tesi és estudiar la relació entre la prevalença de mutacions en el codó 12 de l'oncogèn K-ras i diferents factors ambientals (consum de tabac i alcohol), clínics (antecedents patològics) i genètics (polimorfismes en el gen CYP1B1), en pacients amb ADP. Metodologia La tesi s'emmarca en el projecte PANKRAS II, un estudi multicèntric prospectiu sobre el paper de les mutacions en l'oncogèn K-ras i altres alteracions genètiques en el diagnòstic, el pronòstic i l'etiologia del càncer de pàncrees exocrí. Es van reclutar 602 pacients procedents de 5 hospitals generals del nord-est de la península ibèrica amb patologies relacionades amb el pàncrees, dels quals 185 eren pacients amb ADP. Es va entrevistar personalment més del 85% dels pacients per obtenir informació sociodemogràfica, clínica (antecedents patològics i història familiar de càncer) o sobre els seus estils de vida (dieta, ocupació o hàbits tòxics); paral·lelament es van revisar les històries clíniques d'aquests pacients. Finalment es van realitzar anàlisis moleculars de gens implicats en el procés de carcinogènesi pancreàtica (K-ras, TP53, p-16/CDKN2, SMAD4/DPC4, BRCA2 o CFTR). L'anàlisi de l'associació entre la prevalença de mutacions en l'oncogèn K-ras i els diferents factors clínics, ambientals i genètics s'ha realitzat mitjançant regressió logística no condicional. Resultats i discussió Tot i que el consum de tabac és el factor de risc més ben establert i les mutacions en l'oncogèn K-ras un esdeveniment fonamental en l'etiologia de l'ADP, els nostres resultats mostren que no existeix associació entre ambdós factors. Els carcinògens del tabac presents en el teixit pancreàtic, les nitrosamines, serien les responsables d'alteracions en gens que intervenen en estadis més tardans del desenvolupament del càncer; alhora, altres carcinògens del tabac amb capacitat per activar K-ras, com els hidrocarburs aromàtics policíclics, no tindrien el pàncrees com a òrgan diana. Els carcinògens del tabac intervenen en la carcinogènesi pancreàtica per vies alternatives a l'activació de K-ras. El gen citocrom P4501B1 (CYP1B1) codifica un enzim metabolitzador de carcinògens i estrògens amb un rol important en la bioactivació de procarcinògens ambientals. En les reaccions de detoxificació es generen productes capaços d'unir-se al DNA formant adductes, que poden ser els responsables de les mutacions activadores en l'oncogèn K-ras. Els nostres resultats mostren que el genotip homozigot per l'al·lel valina en el locus m1 del gen CYP1B1, augmenta de risc de tenir un ADP amb mutacions en l'oncogèn K-ras; aquest genotip estaria associat a una activitat detoxificadora més pobra i, en conseqüència, a un procés deficient de biotransformació, metabolització i eliminació de tòxics de l'organisme, que serien l'origen de mutacions en l'oncogèn K-ras. Les mutacions en l'oncogèn K-ras són presents en estadis molt inicials del procés carcinogènic pancreàtic, i també en el teixit de pacients amb pancreatitis o diabetis; ambdues patologies considerades possibles factors de risc per l'ADP. Els nostres resultats mostren que els antecedents patològics de diabetis tipus 2 (DM-2) i de pancreatitis no són més freqüents en els casos d'ADP amb mutacions a K-ras. Així doncs, en pacients d'ADP, tant els antecedents de DM-2 com els de pancreatitis semblen estar associats amb vies d'activació de la carcinogènesi pancreàtica independents de K-ras, potser lligats al dany que pateix el teixit pancreàtic com a conseqüència de la inflamació crònica a la que està sotmès i a mediadors de la resposta inflamatòria, entre d'altres. Tot i que es discuteix el paper del consum d'alcohol en la carcinogènesi pancreàtica, tant l'etanol com el seu metabòlit, l'acetaldehid, estan reconeguts com a carcinògens en humans. Els nostres resultats mostren que el consum d'alcohol al llarg de la vida està associat amb la presència de mutacions en l'oncogèn K-ras en pacients amb ADP. Els efectes carcinogènics i mutagènics de l'etanol i l'acetaldehid podrien jugar un paper important en l'aparició de les mutacions en l'oncogèn K-ras en l'epiteli pancreàtic., Background The primary prevention of pancreatic ductal adenocarcinoma (PDA) cancer is hampered by limited knowledge on its etiology. Tobacco consumption is the best established risk factor, but it explains only a small fraction of cases. It is currently being discussed the role of other etiologic factors including diet, medical history, environmental and occupational exposures, or genetic susceptibility. Activating point mutations in the K-ras oncogene are one of the fundamental genetic events leading to PDA; at diagnosis, about 80% of PDA cases harbour mutations in codon 12 of K-ras. Depending on the cellular and molecular context, oncogenic K-ras activation can result in a wide variety of responses ranging from the activation of a senescence programme to an increased cell proliferation and inhibition of apoptosis. Ras genes are critical targets for chemical carcinogens; K-ras-mutated and wild-type cancers may develop through pathways involving different gene-environment interactions. Although mutations in K-ras are the most frequent alteration of oncogenes in human cancer, the potential lifestyle and environmental influences on their occurrence and persistence are largely unknown. The main objective of the present thesis is to assess the relationship between activating mutations in codon 12 of the K-ras oncogene and environmental, clinical, and genetic factors, (specifically tobacco and alcohol consumption, medical history and genetic polymorphisms in CYP1B1) in patients with PDA. Methodology This thesis is developed in the context of the PANKRAS II project, a multicentre prospective study on the role of mutations in the K-ras oncogene and other genetic alterations in the diagnosis, prognosis and etiology of exocrine pancreatic cancer. A total of 602 subjects were recruited at five general hospitals in the eastern Mediterranean part of Spain; among them, 185 were incident cases of PDA. Over 85% of the patients were interviewed face-to-face during hospital stay, close to the time of diagnosis. Interviews included questions about lifestyle, past clinical history, symptoms, occupation, diet, coffee, alcohol and tobacco consumption. A structured form was used to collect clinicopathological information from medical records, including details on diagnostic procedures, laboratory results and follow-up care. Molecular analyses of genes involved in pancreatic carcinogenesis were also undertaken (i.e., K-ras, TP53, p-16/CDKN2, SMAD4/DPC4, BRCA2 or CFTR). The association between the presence of K-ras mutations and clinical, environmental and genetic factors was assessed by unconditional logistic regression. Results and discussionWhile both smoking and K-ras mutations have important roles in the etiopathogenesis of PDA, our results show no association between the presence of K-ras mutations and tobacco consumption in PDA patients; the two processes may act independently in pancreatic carcinogenesis. Carcinogens from tobacco smoke detected in pancreatic tissue (nitrosamines) might be the responsible of other genetic alterations that act late in the carcinogenic process. On the other hand, pancreatic tissue is not a target organ for tobacco carcinogens that could activate oncogenic K-ras (such as polycyclic aromatic hydrocarbons). Tobacco does not play a major part in the acquisition of K-ras mutations in the pancreatic epithelium. Cytochrome P4501B1 (CYP1B1) is a carcinogen and estrogen-metabolizing enzyme with an important role in the bioactivation of some environmental procarcinogens. The oxidant steps catalyzed by this enzyme create more reactive intermediates that are able to bind with DNA, leading to DNA adduct formation and genetic mutations. Our results suggest that CYP1B1 polymorphisms might influence interindividual differences in susceptibility to pancreatic cancer by the acquisition of K-ras mutations. Val/Val genotype increases the probability of having a K-ras mutated PDA; this genotype might be associated with poor detoxification activity and, consequently, with an impaired elimination of some environmental toxics that can react with DNA to form stable adducts, which may favor mutations in K-ras. Activating point mutations in the K-ras oncogene are present in early stages of the PDA development, and have been also detected in pancreatic tissue from patients with diabetes and pancreatitis, both considered as risk factors for PDA. Our results show no association between the presence of K-ras mutations and medical history of diabetes or pancreatitis in PDA patients. Medical history of pancreatitis and diabetes may favor pancreatic carcinogenesis through pathways independent of K-ras activation; chronic inflammation causes a gradual damage of pancreatic tissue that might contribute to carcinogenic transformation of acinar pancreatic cells through molecular alterations not involving K-ras mutations. Although the role of alcohol in pancreatic carcinogenesis remains inconclusive, there is sufficient evidence for the carcinogenicity of ethanol and acetaldehyde. Our results show a positive relationship between lifetime history of alcohol consumption and the prevalence at diagnosis of K-ras mutations in PDA patients. Acetaldehyde, a cytotoxic, mutagenic, and carcinogenic metabolite of ethanol, is responsible for tumor enhancing effects leading to cell proliferation; it can also bind to DNA, leading to the formation of stable DNA adducts that could cause replication errors and mutations in oncogenes and tumor suppressor genes, and K-ras seems to be one of them.

Published
2009

189. Association Between Oxytocin Receptor Genotype, Maternal Care, and Eating Disorder Behaviours in a Community Sample of Women.

Author

Micali, Nadia, Crous‐Bou, Marta, Treasure, Janet, and Lawson, Elizabeth A.

Subjects
*CONFIDENCE intervals, *EATING disorders, *GENETIC polymorphisms, *LONGITUDINAL method, *OXYTOCIN, *RESEARCH funding, *LOGISTIC regression analysis, *ODDS ratio, *GENOTYPES, *PREGNANCY
Abstract

This study aimed to investigate associations between oxytocin receptor gene ( OXT-R) polymorphisms (rs53576 and rs2254298), their interaction with maternal care (GxE), and ED behaviours in a community sample. We studied 3698 women from the Avon Longitudinal Study of Parents and Children (ALSPAC) who participated in a two-phase prevalence study of lifetime ED and had genotype data. The GG rs53576 genotype was associated with binge eating and purging, and the rs2254298 AG/AA genotype with restrictive eating lifetime. In addition, the rs2254298 AG/AA genotype interacted with poor maternal care to increase the odds of binge eating and purging (odds ratio = 4.40 (95% confidence intervals: 1.11-17.4)). This study replicates previous findings of an association between OXT-R polymorphisms and ED, and it is the first to show an interaction between OXT-R genotype and poor maternal care. As such, these findings highlight the important role of oxytocin in understanding the pathophysiology of ED. © 2016 The Authors European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd [ABSTRACT FROM AUTHOR]

Published
2017
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191. Large differences in global transcriptional regulatory programs of normal and tumor colon cells

Author

Cordero, David, primary, Solé, Xavier, additional, Crous-Bou, Marta, additional, Sanz-Pamplona, Rebeca, additional, Paré-Brunet, Laia, additional, Guinó, Elisabet, additional, Olivares, David, additional, Berenguer, Antonio, additional, Santos, Cristina, additional, Salazar, Ramón, additional, Biondo, Sebastiano, additional, and Moreno, Víctor, additional

Published
2014
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193. Exome-Wide Association Study of Endometrial Cancer in a Multiethnic Population

Author

Chen, Maxine M., primary, Crous-Bou, Marta, additional, Setiawan, Veronica W., additional, Prescott, Jennifer, additional, Olson, Sara H., additional, Wentzensen, Nicolas, additional, Black, Amanda, additional, Brinton, Louise, additional, Chen, Chu, additional, Chen, Constance, additional, Cook, Linda S., additional, Doherty, Jennifer, additional, Friedenreich, Christine M., additional, Hankinson, Susan E., additional, Hartge, Patricia, additional, Henderson, Brian E., additional, Hunter, David J., additional, Le Marchand, Loic, additional, Liang, Xiaolin, additional, Lissowska, Jolanta, additional, Lu, Lingeng, additional, Orlow, Irene, additional, Petruzella, Stacey, additional, Polidoro, Silvia, additional, Pooler, Loreall, additional, Rebbeck, Timothy R., additional, Risch, Harvey, additional, Sacerdote, Carlotta, additional, Schumacher, Frederick, additional, Sheng, Xin, additional, Shu, Xiao-ou, additional, Weiss, Noel S., additional, Xia, Lucy, additional, Van Den Berg, David, additional, Yang, Hannah P., additional, Yu, Herbert, additional, Chanock, Stephen, additional, Haiman, Christopher, additional, Kraft, Peter, additional, and De Vivo, Immaculata, additional

Published
2014
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194. Aberrant gene expression in mucosa adjacent to tumor reveals a molecular crosstalk in colon cancer

Author

Sanz-Pamplona, Rebeca, primary, Berenguer, Antoni, additional, Cordero, David, additional, Molleví, David G, additional, Crous-Bou, Marta, additional, Sole, Xavier, additional, Paré-Brunet, Laia, additional, Guino, Elisabet, additional, Salazar, Ramón, additional, Santos, Cristina, additional, de Oca, Javier, additional, Sanjuan, Xavier, additional, Rodriguez-Moranta, Francisco, additional, and Moreno, Victor, additional

Published
2014
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195. Autores

Author

Abecia Inchaurregui, Luis Carlos, Abreu Rodríguez, Rossana, Aguinaga Ontoso, Enrique, Aibar Remón, Carlos, Alberdi Sudupe, Jesús, Alfonso Sánchez, José Luis, Alguacil Ojeda, Juan, Almaraz Gómez, Ana, Altet Gómez, María Neus, Álvarez Marante, Roberto, Álvarez-Dardet Díaz, Carlos, Álvarez-Ruiz, Juan Carlos, Amezcua Prieto, Carmen, Aranaz Andrés, Jesús M.ª, Aranceta Bartrina, Javier, Arcos González, Pedro, Arévalo Morales, M.ª Pilar, Arias Rodríguez, Ángeles, Armadans Gil, Lluís, Badenier Bustamante, Osvaldo, Ballina García, Francisco Javier, Baltar Trabazo, José Manuel, Banegas Banegas, José Ramón, Barros Dios, Juan Miguel, Bes-Rastrollo, Maira, Bolúmar Montrull, Francisco, Borràs López, Eva, Brugos Larumbe, Antonio, Bueno Cavanillas, Aurora, Caamaño Isorna, Francisco, Calle Purón, María Elisa, Calleja Cabeza, Patricia, Campayo Rojas, Francisco Javier, Campins Martí, Magda, Carlos Chillerón, Silvia, Carrasco Garrido, Pilar, Castro Delgado, Rafael, Castro Hernández, Beatriz, Conde Herrera, Manuel, Corella Piquer, Dolores, Cores Calvo, Juan, Crous Bou, Marta, Davó Blanes, M.ª Carmen, de Irala Estévez, Jokin, de Juanes Pardo, José Ramón, del Barrio Fernández, José Luis, del Rey Calero, Juan, Delgado Rodríguez, Miguel, Díaz Molina, Carmen, Dierssen Sotos, Trinidad, Díez Sebastián, Jesús, Díez-Gañán, Lucía, Domínguez García, Ángela, Domínguez Rojas, Vicente, Donat-Vargas, Carolina, Doreste Alonso, Jorge Luis, Duran Jordà, Xavier, Escribá Aguir, Vicenta, Esguep Sarah, Alfredo, Espigares García, Miguel, Espigares Rodríguez, Elena, Farouk Allam, Mohamed, Fernández Muñoz, Esteve, Fernández-Crehuet Navajas, Joaquín, Fernández-Crehuet Navajas, Rafael, Fernández-Crehuet Serrano, José Luis, Fernández-Crehuet Serrano, Pablo, Ferreira Herdeiro, María Teresa, Figueiras Guzmán, Adolfo, Fuentes Almendras, Margarita, Gallardo Pino, Carmen, García Barbero, Milagros, García Benavides, Fernando, García Caballero, Juan, García de la Hera, Manuela, García López, Eva María, García Martín, Miguel, García Rodríguez, Antonio, Gea Sánchez, Alfredo, Gestal Otero, Juan Jesús, Gestal Romaní, Santiago, Gil de Miguel, Ángel, Gil Prieto, Ruth, Gil-González, Diana, Gili Miner, Miguel, Gómez Acebo, Inés, Gómez-Aracena, Jorge, Gómez-Gracia, Enrique, González Iglesias, Marta Clara, Graciani Pérez-Regadera, Auxiliadora, Guallar Castillón, Pilar, Guillén Grima, Francisco, Guillén Solvas, José Francisco, Gutiérrez Bedmar, Mario, Gutiérrez-Fisac, Juan Luis, Harris, Meggan, Henríquez Sánchez, Patricia, Hernández Aguado, Ildefonso, Hernández Mejía, Radhamés, Herruzo Cabrera, Rafael, Herruzo Priego, Irene, Iglesias Amorín, José Luis, Jiménez García, Rodrigo, Jiménez Mejías, Eladio, Jiménez Moleón, José Juan, Jurado Chacón, Dolores, Lana Pérez, Alberto, Lardelli Claret, Pablo, Latorre-Arteaga, Sergio, Lecuona Fernández, María, Llinás Santacreu, Gilberto, Llopis González, Agustín, Llorca Díaz, Javier, López de Andrés, Ana, López García, Esther, López-Gigosos, Rosa María, López González, María Luisa, López Jurado, Lázaro, López-del Burgo, Cristina, Lumbreras Lacarra, Blanca, Luna del Castillo, Juan de Dios, Malvar Pintos, Alberto, Mariscal Larrubia, Alberto, Martín Moreno, José María, Martín Sánchez, Vicente, Martín-Calvo, Nerea, Martínez-González, Miguel Ángel, Martínez Ruiz, Virginia, Martínez Vizcaíno, Vicente, Mendiola Olivares, Jaime, Miqueleiz Autor, Estrella, Monasterio Otero, Adolfo Alejandro, Monge Corella, Susana, Montes Martínez, Agustín, Morales Suárez-Varela, María M., Moreno Abril, Obdulia, Moreno Roldán, Elena, Moya Geromini, Ángeles, Muñiz Saborido, José Ramón, Muñoz Bravo, Carlos, Navarrete Muñoz, Eva María, Olmedo Requena, Rocío, Ortiz Moncada, Rocío, Otero Cordeiro, Francisco Javier, Pastor Valero, María, Peña Sánchez de Rivera, José María, Pértega Díaz, Sonia, Pita Fernández, Salvador, Porta Serra, Miquel, Portolés Reparaz, Olga, Regidor Poyatos, Enrique, Ribas Barba, Lourdes, Río Sánchez, Isabel, Rodríguez Álvarez, Cristobalina, Rodríguez Arenas, M.ª Ángeles, Rodríguez Artalejo, Fernando, Rodríguez Cundín, Paz, Rodríguez Martínez, Marisol, Ronda Pérez, Elena, Rosell Aguilar, Ignacio, Ruano Rodríguez, Cristina, Ruiz Cantero, María Teresa, Ruiz-Canela López, Miguel, Salleras Sanmartí, Lluís, Saltó Cerezuela, Esteve, Sánchez Fernández, Luis Vicente, Sánchez Villegas, Almudena, Sastre Gervás, Isabel, Serra Majem, Lluís, Serrano del Castillo, Amparo, Sillero Arenas, María, Sorlí Guerola, José Vicente, Sotodosos Carpintero, Mercedes, Takkouche, Bahi, Taracido Trunk, Margarita, Tardón García, Adonina, Teijeiro Dacal, María José, Toledo Atucha, Estefanía A., Torner Gracia, Nuria, Torres Cantero, Alberto Manuel, Valcárcel Rivera, Yolanda, Vaqué Rafart, Josep, Villar Álvarez, Fernando, Vioque López, Jesús, and Vizcaíno Alcaide, María José

Published
2016
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196. Influències clíniques i ambientals en la prevalença de mutacions en l'oncogèn K-ras en pacients amb adenocarcinoma ductal de pàncrees

Author

Porta, Miquel, Crous Bou, Marta, Porta, Miquel, and Crous Bou, Marta

Abstract

Descripció del recurs: 27 gener 2010, Antecedents La prevenció primària de l'adenocarcinoma ductal de pàncrees (ADP) està limitada per la falta de coneixement sobre la seva etiologia. El factor de risc més ben establert és el consum de tabac, però explica només una petita proporció de casos. Es discuteix el paper d'altres factors etiològics com els antecedents patològics de diabetis i pancreatitis, la dieta, determinades exposicions ambientals o laborals, i els factors hereditaris. Mutacions puntuals en l'oncogèn K-ras, i la seva conseqüent activació, són presents en més del 80% dels casos d'ADP; és un dels esdeveniments genètics fonamentals perquè el càncer tingui lloc. L'activació d'aquest oncogèn dóna lloc a gran varietat de respostes, des de l'augment de la proliferació cel·lular fins a la inhibició de l'apoptosi, en funció del context cel·lular. Els gens Ras són dianes crítiques per als carcinògens químics; els càncers de pàncrees amb i sense mutacions en l'oncogèn K-ras probablement es desenvolupen a partir de diferents interaccions gen-ambient. Tot i això, els estils de vida i les exposicions ambientals que poden influir en la presència de mutacions en el gen K-ras són pràcticament desconeguts. L'objectiu general d'aquesta tesi és estudiar la relació entre la prevalença de mutacions en el codó 12 de l'oncogèn K-ras i diferents factors ambientals (consum de tabac i alcohol), clínics (antecedents patològics) i genètics (polimorfismes en el gen CYP1B1), en pacients amb ADP. Metodologia La tesi s'emmarca en el projecte PANKRAS II, un estudi multicèntric prospectiu sobre el paper de les mutacions en l'oncogèn K-ras i altres alteracions genètiques en el diagnòstic, el pronòstic i l'etiologia del càncer de pàncrees exocrí. Es van reclutar 602 pacients procedents de 5 hospitals generals del nord-est de la península ibèrica amb patologies relacionades amb el pàncrees, dels quals 185 eren pacients amb ADP. Es va entrevistar personalment més del 85% dels pacients per obtenir informació sociodemogràfica, clí, Background The primary prevention of pancreatic ductal adenocarcinoma (PDA) cancer is hampered by limited knowledge on its etiology. Tobacco consumption is the best established risk factor, but it explains only a small fraction of cases. It is currently being discussed the role of other etiologic factors including diet, medical history, environmental and occupational exposures, or genetic susceptibility. Activating point mutations in the K-ras oncogene are one of the fundamental genetic events leading to PDA; at diagnosis, about 80% of PDA cases harbour mutations in codon 12 of K-ras. Depending on the cellular and molecular context, oncogenic K-ras activation can result in a wide variety of responses ranging from the activation of a senescence programme to an increased cell proliferation and inhibition of apoptosis. Ras genes are critical targets for chemical carcinogens; K-ras-mutated and wild-type cancers may develop through pathways involving different gene-environment interactions. Although mutations in K-ras are the most frequent alteration of oncogenes in human cancer, the potential lifestyle and environmental influences on their occurrence and persistence are largely unknown. The main objective of the present thesis is to assess the relationship between activating mutations in codon 12 of the K-ras oncogene and environmental, clinical, and genetic factors, (specifically tobacco and alcohol consumption, medical history and genetic polymorphisms in CYP1B1) in patients with PDA. Methodology This thesis is developed in the context of the PANKRAS II project, a multicentre prospective study on the role of mutations in the K-ras oncogene and other genetic alterations in the diagnosis, prognosis and etiology of exocrine pancreatic cancer. A total of 602 subjects were recruited at five general hospitals in the eastern Mediterranean part of Spain; among them, 185 were incident cases of PDA. Over 85% of the patients were interviewed face-to-face during hospital stay, cl

Published
2009

198. Clinical Value of Prognosis Gene Expression Signatures in Colorectal Cancer: A Systematic Review

Author

Sanz-Pamplona, Rebeca, primary, Berenguer, Antoni, additional, Cordero, David, additional, Riccadonna, Samantha, additional, Solé, Xavier, additional, Crous-Bou, Marta, additional, Guinó, Elisabet, additional, Sanjuan, Xavier, additional, Biondo, Sebastiano, additional, Soriano, Antonio, additional, Jurman, Giuseppe, additional, Capella, Gabriel, additional, Furlanello, Cesare, additional, and Moreno, Victor, additional

Published
2012
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199. P-194

Author

García-Esquinas, Esther, primary, Lope, Virginia, additional, Pérez-Gómez, Beatriz, additional, Castaño-Vinyals, Gemma, additional, Gómez-Acebo, Inés, additional, Altzibar, Jone, additional, Ardanaz, Eva, additional, Martín, Vicente, additional, Tardón, Adonina, additional, Alguacil, Juan, additional, Crous-Bou, Marta, additional, Peiró, Rosana, additional, Jiménez-Moleón, José Juan, additional, and Pollán, Marina, additional

Published
2012
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200. P-103

Author

Lope, Virginia, primary, García-Esquinas, Esther, additional, Aragonés, Nuria, additional, Kogevinas, Manolis, additional, Dierssen-Sotos, Trinidad, additional, Altzibar, Jone, additional, Ardanaz, Eva, additional, Martín, Vicente, additional, Tardón, Adonina, additional, Alguacil, Juan, additional, Crous-Bou, Marta, additional, Salas, Dolores, additional, Jiménez-Moleón, José Juan, additional, and Pollán, Marina, additional

Published
2012
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