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3. Molecular Characterization of the Human Stomach Microbiota in Gastric Cancer Patients

Author

Yu, Guoqin, Torres, Javier, Hu, Nan, Medrano-Guzman, Rafael, Herrera-Goepfert, Roberto, Humphrys, Michael S, Wang, Lemin, Wang, Chaoyu, Ding, Ti, Ravel, Jacques, Taylor, Philip R, Abnet, Christian C, and Goldstein, Alisa M

Subjects
Microbiology, Biological Sciences, Genetics, Nutrition, Infectious Diseases, Digestive Diseases - (Peptic Ulcer), Rare Diseases, Cancer, Prevention, Emerging Infectious Diseases, Digestive Diseases, Adult, Aged, Bacteria, China, Female, Gastrointestinal Microbiome, Helicobacter pylori, Humans, Male, Mexico, Middle Aged, Stomach, Stomach Neoplasms, Young Adult, 16S rRNA, KEGG modules, gastric cancer, microbiome, Biochemistry and Cell Biology, Medical microbiology
Abstract

Helicobacter pylori (Hp) is the primary cause of gastric cancer but we know little of its relative abundance and other microbes in the stomach, especially at the time of gastric cancer diagnosis. Here we characterized the taxonomic and derived functional profiles of gastric microbiota in two different sets of gastric cancer patients, and compared them with microbial profiles in other body sites. Paired non-malignant and tumor tissues were sampled from 160 gastric cancer patients with 80 from China and 80 from Mexico. The 16S rRNA gene V3-V4 region was sequenced using MiSeq platform for taxonomic profiles. PICRUSt was used to predict functional profiles. Human Microbiome Project was used for comparison. We showed that Hp is the most abundant member of gastric microbiota in both Chinese and Mexican samples (51 and 24%, respectively), followed by oral-associated bacteria. Taxonomic (phylum-level) profiles of stomach microbiota resembled oral microbiota, especially when the Helicobacter reads were removed. The functional profiles of stomach microbiota, however, were distinct from those found in other body sites and had higher inter-subject dissimilarity. Gastric microbiota composition did not differ by Hp colonization status or stomach anatomic sites, but did differ between paired non-malignant and tumor tissues in either Chinese or Mexican samples. Our study showed that Hp is the dominant member of the non-malignant gastric tissue microbiota in many gastric cancer patients. Our results provide insights on the gastric microbiota composition and function in gastric cancer patients, which may have important clinical implications.

Published
2017

4. 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, Carreon, Tania, Chaffee, Kari G, Chang, I-Shou, Chatterjee, Nilanjan, Chen, Chu, Chen, Constance, Chen, Kexin, Chung, Charles C, Cook, Linda S, Bou, Marta Crous, 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, Goran, 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, Le Marchand, Loic, Li, Donghui, Liang, Xiaolin, Liao, Linda M, Lin, Dongxin, Liu, Jianjun, Lissowska, Jolanta, Lu, Lingeng, Magliocco, Anthony M, and Malats, Nuria

Published
2016

5. 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, Bou, Marta Crous, 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, Berg, David VanDen, 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
Biological Sciences, Genetics, Human Genome, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Aged, Chromosome Aberrations, Female, Genome, Human, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Mosaicism, Neoplasms, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
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

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

Author

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

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

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

Published
2014

7. Data from Genomic Landscape of Somatic Alterations in Esophageal Squamous Cell Carcinoma and Gastric Cancer

Author

Hu, Nan, primary, Kadota, Mitsutaka, primary, Liu, Huaitian, primary, Abnet, Christian C., primary, Su, Hua, primary, Wu, Hailong, primary, Freedman, Neal D., primary, Yang, Howard H., primary, Wang, Chaoyu, primary, Yan, Chunhua, primary, Wang, Lemin, primary, Gere, Sheryl, primary, Hutchinson, Amy, primary, Song, Guohong, primary, Wang, Yuan, primary, Ding, Ti, primary, Qiao, You-Lin, primary, Koshiol, Jill, primary, Dawsey, Sanford M., primary, Giffen, Carol, primary, Goldstein, Alisa M., primary, Taylor, Philip R., primary, and Lee, Maxwell P., primary

Published
2023
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8. Supplementary table 8 from Genomic Landscape of Somatic Alterations in Esophageal Squamous Cell Carcinoma and Gastric Cancer

Author

Hu, Nan, primary, Kadota, Mitsutaka, primary, Liu, Huaitian, primary, Abnet, Christian C., primary, Su, Hua, primary, Wu, Hailong, primary, Freedman, Neal D., primary, Yang, Howard H., primary, Wang, Chaoyu, primary, Yan, Chunhua, primary, Wang, Lemin, primary, Gere, Sheryl, primary, Hutchinson, Amy, primary, Song, Guohong, primary, Wang, Yuan, primary, Ding, Ti, primary, Qiao, You-Lin, primary, Koshiol, Jill, primary, Dawsey, Sanford M., primary, Giffen, Carol, primary, Goldstein, Alisa M., primary, Taylor, Philip R., primary, and Lee, Maxwell P., primary

Published
2023
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9. Supplementary table 6 from Genomic Landscape of Somatic Alterations in Esophageal Squamous Cell Carcinoma and Gastric Cancer

Author

Hu, Nan, primary, Kadota, Mitsutaka, primary, Liu, Huaitian, primary, Abnet, Christian C., primary, Su, Hua, primary, Wu, Hailong, primary, Freedman, Neal D., primary, Yang, Howard H., primary, Wang, Chaoyu, primary, Yan, Chunhua, primary, Wang, Lemin, primary, Gere, Sheryl, primary, Hutchinson, Amy, primary, Song, Guohong, primary, Wang, Yuan, primary, Ding, Ti, primary, Qiao, You-Lin, primary, Koshiol, Jill, primary, Dawsey, Sanford M., primary, Giffen, Carol, primary, Goldstein, Alisa M., primary, Taylor, Philip R., primary, and Lee, Maxwell P., primary

Published
2023
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10. Supplementary table 2 from Genomic Landscape of Somatic Alterations in Esophageal Squamous Cell Carcinoma and Gastric Cancer

Author

Hu, Nan, primary, Kadota, Mitsutaka, primary, Liu, Huaitian, primary, Abnet, Christian C., primary, Su, Hua, primary, Wu, Hailong, primary, Freedman, Neal D., primary, Yang, Howard H., primary, Wang, Chaoyu, primary, Yan, Chunhua, primary, Wang, Lemin, primary, Gere, Sheryl, primary, Hutchinson, Amy, primary, Song, Guohong, primary, Wang, Yuan, primary, Ding, Ti, primary, Qiao, You-Lin, primary, Koshiol, Jill, primary, Dawsey, Sanford M., primary, Giffen, Carol, primary, Goldstein, Alisa M., primary, Taylor, Philip R., primary, and Lee, Maxwell P., primary

Published
2023
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11. Supplementary table 4 from Genomic Landscape of Somatic Alterations in Esophageal Squamous Cell Carcinoma and Gastric Cancer

Author

Hu, Nan, primary, Kadota, Mitsutaka, primary, Liu, Huaitian, primary, Abnet, Christian C., primary, Su, Hua, primary, Wu, Hailong, primary, Freedman, Neal D., primary, Yang, Howard H., primary, Wang, Chaoyu, primary, Yan, Chunhua, primary, Wang, Lemin, primary, Gere, Sheryl, primary, Hutchinson, Amy, primary, Song, Guohong, primary, Wang, Yuan, primary, Ding, Ti, primary, Qiao, You-Lin, primary, Koshiol, Jill, primary, Dawsey, Sanford M., primary, Giffen, Carol, primary, Goldstein, Alisa M., primary, Taylor, Philip R., primary, and Lee, Maxwell P., primary

Published
2023
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12. Table Legend from Genomic Landscape of Somatic Alterations in Esophageal Squamous Cell Carcinoma and Gastric Cancer

Author

Hu, Nan, primary, Kadota, Mitsutaka, primary, Liu, Huaitian, primary, Abnet, Christian C., primary, Su, Hua, primary, Wu, Hailong, primary, Freedman, Neal D., primary, Yang, Howard H., primary, Wang, Chaoyu, primary, Yan, Chunhua, primary, Wang, Lemin, primary, Gere, Sheryl, primary, Hutchinson, Amy, primary, Song, Guohong, primary, Wang, Yuan, primary, Ding, Ti, primary, Qiao, You-Lin, primary, Koshiol, Jill, primary, Dawsey, Sanford M., primary, Giffen, Carol, primary, Goldstein, Alisa M., primary, Taylor, Philip R., primary, and Lee, Maxwell P., primary

Published
2023
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13. Supplementary table 3 from Genomic Landscape of Somatic Alterations in Esophageal Squamous Cell Carcinoma and Gastric Cancer

Author

Hu, Nan, primary, Kadota, Mitsutaka, primary, Liu, Huaitian, primary, Abnet, Christian C., primary, Su, Hua, primary, Wu, Hailong, primary, Freedman, Neal D., primary, Yang, Howard H., primary, Wang, Chaoyu, primary, Yan, Chunhua, primary, Wang, Lemin, primary, Gere, Sheryl, primary, Hutchinson, Amy, primary, Song, Guohong, primary, Wang, Yuan, primary, Ding, Ti, primary, Qiao, You-Lin, primary, Koshiol, Jill, primary, Dawsey, Sanford M., primary, Giffen, Carol, primary, Goldstein, Alisa M., primary, Taylor, Philip R., primary, and Lee, Maxwell P., primary

Published
2023
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14. Supplementary table 5 from Genomic Landscape of Somatic Alterations in Esophageal Squamous Cell Carcinoma and Gastric Cancer

Author

Hu, Nan, primary, Kadota, Mitsutaka, primary, Liu, Huaitian, primary, Abnet, Christian C., primary, Su, Hua, primary, Wu, Hailong, primary, Freedman, Neal D., primary, Yang, Howard H., primary, Wang, Chaoyu, primary, Yan, Chunhua, primary, Wang, Lemin, primary, Gere, Sheryl, primary, Hutchinson, Amy, primary, Song, Guohong, primary, Wang, Yuan, primary, Ding, Ti, primary, Qiao, You-Lin, primary, Koshiol, Jill, primary, Dawsey, Sanford M., primary, Giffen, Carol, primary, Goldstein, Alisa M., primary, Taylor, Philip R., primary, and Lee, Maxwell P., primary

Published
2023
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15. Supplementary table 1 from Genomic Landscape of Somatic Alterations in Esophageal Squamous Cell Carcinoma and Gastric Cancer

Author

Hu, Nan, primary, Kadota, Mitsutaka, primary, Liu, Huaitian, primary, Abnet, Christian C., primary, Su, Hua, primary, Wu, Hailong, primary, Freedman, Neal D., primary, Yang, Howard H., primary, Wang, Chaoyu, primary, Yan, Chunhua, primary, Wang, Lemin, primary, Gere, Sheryl, primary, Hutchinson, Amy, primary, Song, Guohong, primary, Wang, Yuan, primary, Ding, Ti, primary, Qiao, You-Lin, primary, Koshiol, Jill, primary, Dawsey, Sanford M., primary, Giffen, Carol, primary, Goldstein, Alisa M., primary, Taylor, Philip R., primary, and Lee, Maxwell P., primary

Published
2023
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16. Supplementary table 7 from Genomic Landscape of Somatic Alterations in Esophageal Squamous Cell Carcinoma and Gastric Cancer

Author

Hu, Nan, primary, Kadota, Mitsutaka, primary, Liu, Huaitian, primary, Abnet, Christian C., primary, Su, Hua, primary, Wu, Hailong, primary, Freedman, Neal D., primary, Yang, Howard H., primary, Wang, Chaoyu, primary, Yan, Chunhua, primary, Wang, Lemin, primary, Gere, Sheryl, primary, Hutchinson, Amy, primary, Song, Guohong, primary, Wang, Yuan, primary, Ding, Ti, primary, Qiao, You-Lin, primary, Koshiol, Jill, primary, Dawsey, Sanford M., primary, Giffen, Carol, primary, Goldstein, Alisa M., primary, Taylor, Philip R., primary, and Lee, Maxwell P., primary

Published
2023
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17. Supplementary Figure 1 and Supplementary Tables 1 through 4 from PLCE1 mRNA and Protein Expression and Survival of Patients with Esophageal Squamous Cell Carcinoma and Gastric Adenocarcinoma

Author

Li, Wen-Qing, primary, Hu, Nan, primary, Burton, Victoria H., primary, Yang, Howard H., primary, Su, Hua, primary, Conway, Catherine M., primary, Wang, Lemin, primary, Wang, Chaoyu, primary, Ding, Ti, primary, Xu, Yi, primary, Giffen, Carol, primary, Abnet, Christian C., primary, Goldstein, Alisa M., primary, Hewitt, Stephen M., primary, and Taylor, Philip R., primary

Published
2023
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19. 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, Jr., 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., Jr, 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, III, 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, III, 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
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22. Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations

Author

Wu, Chen, Wang, Zhaoming, Song, Xin, Feng, Xiao-Shan, Abnet, Christian C, He, Jie, Hu, Nan, Zuo, Xian-Bo, Tan, Wen, Zhan, Qimin, Hu, Zhibin, He, Zhonghu, Jia, Weihua, Zhou, Yifeng, Yu, Kai, Shu, Xiao-Ou, Yuan, Jian-Min, Zheng, Wei, Zhao, Xue-Ke, Gao, She-Gan, Yuan, Zhi-Qing, Zhou, Fu-You, Fan, Zong-Min, Cui, Ji-Li, Lin, Hong-Li, Han, Xue-Na, Li, Bei, Chen, Xi, Dawsey, Sanford M, Liao, Linda, Lee, Maxwell P, Ding, Ti, Qiao, You-Lin, Liu, Zhihua, Liu, Yu, Yu, Dianke, Chang, Jiang, Wei, Lixuan, Gao, Yu-Tang, Koh, Woon-Puay, Xiang, Yong-Bing, Tang, Ze-Zhong, Fan, Jin-Hu, Han, Jing-Jing, Zhou, Sheng-Li, Zhang, Peng, Zhang, Dong-Yun, Yuan, Yuan, Huang, Ying, Liu, Chunling, Zhai, Kan, Qiao, Yan, Jin, Guangfu, Guo, Chuanhai, Fu, Jianhua, Miao, Xiaoping, Lu, Changdong, Yang, Haijun, Wang, Chaoyu, Wheeler, William A, Gail, Mitchell, Yeager, Meredith, Yuenger, Jeff, Guo, Er-Tao, Li, Ai-Li, Zhang, Wei, Li, Xue-Min, Sun, Liang-Dan, Ma, Bao-Gen, Li, Yan, Tang, Sa, Peng, Xiu-Qing, Liu, Jing, Hutchinson, Amy, Jacobs, Kevin, Giffen, Carol, Burdette, Laurie, Fraumeni, Jr, Joseph F, Shen, Hongbing, Ke, Yang, Zeng, Yixin, Wu, Tangchun, Kraft, Peter, Chung, Charles C, Tucker, Margaret A, Hou, Zhi-Chao, Liu, Ya-Li, Hu, Yan-Long, Liu, Yu, Wang, Li, Yuan, Guo, Chen, Li-Sha, Liu, Xiao, Ma, Teng, Meng, Hui, Sun, Li, Li, Xin-Min, Li, Xiu-Min, Ku, Jian-Wei, Zhou, Ying-Fa, Yang, Liu-Qin, Wang, Zhou, Li, Yin, Qige, Qirenwang, Yang, Wen-Jun, Lei, Guang-Yan, Chen, Long-Qi, Li, En-Min, Yuan, Ling, Yue, Wen-Bin, Wang, Ran, Wang, Lu-Wen, Fan, Xue-Ping, Zhu, Fang-Heng, Zhao, Wei-Xing, Mao, Yi-Min, Zhang, Mei, Xing, Guo-Lan, Li, Ji-Lin, Han, Min, Ren, Jing-Li, Liu, Bin, Ren, Shu-Wei, Kong, Qing-Peng, Li, Feng, Sheyhidin, Ilyar, Wei, Wu, Zhang, Yan-Rui, Feng, Chang-Wei, Wang, Jin, Yang, Yu-Hua, Hao, Hong-Zhang, Bao, Qi-De, Liu, Bao-Chi, Wu, Ai-Qun, Xie, Dong, Yang, Wan-Cai, Wang, Liang, Zhao, Xiao-Hang, Chen, Shu-Qing, Hong, Jun-Yan, Zhang, Xue-Jun, Freedman, Neal D, Goldstein, Alisa M, Lin, Dongxin, Taylor, Philip R, Wang, Li-Dong, and Chanock, Stephen J

Published
2014
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23. Additional file of Genome wide analysis of DNA copy number neutral loss of heterozygosity (CNNLOH) and its relation to gene expression in esophageal squamous cell carcinoma

Author

Hu, Nan, Clifford, Robert J, Yang, Howard H, Chaoyu Wang, Goldstein, Alisa M, Ding, Ti, Taylor, Philip R, and Lee, Maxwell P

Abstract

Additional file of Genome wide analysis of DNA copy number neutral loss of heterozygosity (CNNLOH) and its relation to gene expression in esophageal squamous cell carcinoma

Published
2021
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25. Additional file 2 of Genome wide analysis of DNA copy number neutral loss of heterozygosity (CNNLOH) and its relation to gene expression in esophageal squamous cell carcinoma

Author

Hu, Nan, Clifford, Robert J, Yang, Howard H, Chaoyu Wang, Goldstein, Alisa M, Ding, Ti, Taylor, Philip R, and Lee, Maxwell P

Subjects
body regions, nervous system, fungi
Abstract

Additional file 2: Figure S2. The relationship between genes, Affymetrix expression probesets, and SNPs. (PDF 238 KB)

Published
2021
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26. Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions

Author

Wu, Chen, Kraft, Peter, Zhai, Kan, Chang, Jiang, Wang, Zhaoming, Li, Yun, Hu, Zhibin, He, Zhonghu, Jia, Weihua, Abnet, Christian C, Liang, Liming, Hu, Nan, Miao, Xiaoping, Zhou, Yifeng, Liu, Zhihua, Zhan, Qimin, Liu, Yu, Qiao, Yan, Zhou, Yuling, Jin, Guangfu, Guo, Chuanhai, Lu, Changdong, Yang, Haijun, Fu, Jianhua, Yu, Dianke, Freedman, Neal D, Ding, Ti, Tan, Wen, Goldstein, Alisa M, Wu, Tangchun, Shen, Hongbing, Ke, Yang, Zeng, Yixin, Chanock, Stephen J, Taylor, Philip R, and Lin, Dongxin

Published
2012
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27. Case–case comparison of smoking and alcohol risk associations with Epstein–Barr virus-positive gastric cancer

Author

Camargo, Constanza M., Koriyama, Chihaya, Matsuo, Keitaro, Kim, Woo-Ho, Herrera-Goepfert, Roberto, Liao, Linda M., Yu, Jun, Carrasquilla, Gabriel, Sung, Joseph J.Y., Alvarado-Cabrero, Isabel, Lissowska, Jolanta, Meneses-Gonzalez, Fernando, Yatabe, Yashushi, Ding, Ti, Hu, Nan, Taylor, Philip R., Morgan, Douglas R., Gulley, Margaret L., Torres, Javier, Akiba, Suminori, and Rabkin, Charles S.

Published
2014
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28. Genetic variants in fas signaling pathway genes and risk of gastric cancer

Author

Hyland, Paula L., Lin, Shih-Wen, Hu, Nan, Zhang, Han, Wang, Lemin, Su, Hua, Wang, Chaoyu, Ding, Ti, Tang, Ze-Zhong, Fan, Jin-Hu, Qiao, You-Lin, Xiong, Xiaoqin, Wheeler, William, Giffen, Carol, Yu, Kai, Yuenger, Jeff, Burdett, Laurie, Wang, Zhaoming, Chanock, Stephen J., Tucker, Margaret A., Dawsey, Sanford M., Freedman, Neal D., Goldstein, Alisa M., Abnet, Christian C., and Taylor, Philip R.

Published
2014
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30. Genetic variants in DNA repair pathway genes and risk of esophageal squamous cell carcinoma and gastric adenocarcinoma in a Chinese population

Author

Li, Wen-Qing, Hu, Nan, Hyland, Paula L., Gao, Ying, Wang, Zhao-Ming, Yu, Kai, Su, Hua, Wang, Chao-Yu, Wang, Le-Min, Chanock, Stephen J., Burdett, Laurie, Ding, Ti, Qiao, You-Lin, Fan, Jin-Hu, Wang, Yuan, Xu, Yi, Shi, Jian-Xin, Gu, Fangyi, Wheeler, William, Xiong, Xiao-Qin, Giffen, Carol, Tucker, Margaret A., Dawsey, Sanford M., Freedman, Neal D., Abnet, Christian C., Goldstein, Alisa M., and Taylor, Philip R.

Published
2013
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32. Genotypic variants at 2q33 and risk of esophageal squamous cell carcinoma in China: a meta-analysis of genome-wide association studies

Author

Abnet, Christian C., Wang, Zhaoming, Song, Xin, Hu, Nan, Zhou, Fu-You, Freedman, Neal D., Li, Xue-Min, Yu, Kai, Shu, Xiao-Ou, Yuan, Jian-Min, Zheng, Wei, Dawsey, Sanford M., Liao, Linda M., Lee, Maxwell P., Ding, Ti, Qiao, You-Lin, Gao, Yu-Tang, Koh, Woon-Puay, Xiang, Yong-Bing, Tang, Ze-Zhong, Fan, Jin-Hu, Chung, Charles C., Wang, Chaoyu, Wheeler, William, Yeager, Meredith, Yuenger, Jeff, Hutchinson, Amy, Jacobs, Kevin B., Giffen, Carol A., Burdett, Laurie, Fraumeni, Joseph F., Jr, Tucker, Margaret A., Chow, Wong-Ho, Zhao, Xue-Ke, Li, Jiang-Man, Li, Ai-Li, Sun, Liang-Dan, Wei, Wu, Li, Ji-Lin, Zhang, Peng, Li, Hong-Lei, Cui, Wen-Yan, Wang, Wei-Peng, Liu, Zhi-Cai, Yang, Xia, Fu, Wen-Jing, Cui, Ji-Li, Lin, Hong-Li, Zhu, Wen-Liang, Liu, Min, Chen, Xi, Chen, Jie, Guo, Li, Han, Jing-Jing, Zhou, Sheng-Li, Huang, Jia, Wu, Yue, Yuan, Chao, Huang, Jing, Ji, Ai-Fang, Kul, Jian-Wei, Fan, Zhong-Min, Wang, Jian-Po, Zhang, Dong-Yun, Zhang, Lian-Qun, Zhang, Wei, Chen, Yuan-Fang, Ren, Jing-Li, Li, Xiu-Min, Dong, Jin-Cheng, Xing, Guo-Lan, Guo, Zhi-Gang, Yang, Jian-Xue, Mao, Yi-Ming, Yuan, Yuan, Guo, Er-Tao, Zhang, Wei, Hou, Zhi-Chao, Liu, Jing, Li, Yan, Tang, Sa, Chang, Jia, Peng, Xiu-Qin, Han, Min, Yin, Wan-Li, Liu, Ya-Li, Hu, Yan-Long, Liu, Yu, Yang, Liu-Qin, Zhu, Fu-Guo, Yang, Xiu-Feng, Feng, Xiao-Shan, Wang, Zhou, Li, Yin, Gao, She-Gan, Liu, Hai-Lin, Yuan, Ling, Jin, Yan, Zhang, Yan-Rui, Sheyhidin, Ilyar, Li, Feng, Chen, Bao-Ping, Ren, Shu-Wei, Liu, Bin, Li, Dan, Zhang, Gao-Fu, Yue, Wen-Bin, Feng, Chang-Wei, Qige, Qirenwang, Zhao, Jian-Ting, Yang, Wen-Jun, Lei, Guang-Yan, Chen, Long-Qi, Li, En-Min, Xu, Li-Yan, Wu, Zhi-Yong, Bao, Zhi-Qin, Chen, Ji-Li, Li, Xian-Chang, Zhuang, Xiang, Zhou, Ying-Fa, Zuo, Xian-Bo, Dong, Zi-Ming, Wang, Lu-Wen, Fan, Xue-Pin, Wang, Jin, Zhou, Qi, Ma, Guo-Shun, Zhang, Qin-Xian, Liu, Hai, Jian, Xin-Ying, Lian, Sin-Yong, Wang, Jin-Sheng, Chang, Fu-Bao, Lu, Chang-Dong, Miao, Jian-Jun, Chen, Zhi-Guo, Wang, Ran, Guo, Ming, Fan, Zeng-Lin, Tao, Ping, Liu, Tai-Jing, Wei, Jin-Chang, Kong, Qing-Peng, Fan, Lei, Wang, Xian-Zeng, Gao, Fu-Sheng, Wang, Tian-Yun, Xie, Dong, Wang, Li, Chen, Shu-Qing, Yang, Wan-Cai, Hong, Jun-Yan, Wang, Liang, Qiu, Song-Liang, Goldstein, Alisa M., Yuan, Zhi-Qing, Chanock, Stephen J., Zhang, Xue-Jun, Taylor, Philip R., and Wang, Li-Dong

Published
2012
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33. InterSCOPE Study: Associations Between Esophageal Squamous Cell Carcinoma and Human Papillomavirus Serological Markers

Author

Sitas, Freddy, Egger, Sam, Urban, Margaret I., Taylor, Philip R., Abnet, Christian C., Boffetta, Paolo, O’Connell, Dianne L., Whiteman, David C., Brennan, Paul, Malekzadeh, Reza, Pawlita, Michael, Dawsey, Sanford M., Waterboer, Tim, Webb, Penelope M., Green, Adèle C., Hayward, Nicholas K., Zaridze, David, Holcatova, Ivana, Mates, Dana, Szeszenia-Dabrowska, Neonila, Ferro, Gilles, Janout, Vladimir, Curado, Maria Paula, Menezes, Ana Maria, Koifman, Sergio, Islami, Farhad, Nasrollahzadeh, Dariush, Hu, Nan, Goldstein, Alisa M., Gao, Ying, Ding, Ti, and Kamangar, Farin

Published
2012
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34. Corrigendum: Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions

Author

Wu, Chen, Kraft, Peter, Zhai, Kan, Chang, Jiang, Wang, Zhaoming, Li, Yun, Hu, Zhibin, He, Zhonghu, Jia, Weihua, Abnet, Christian C, Liang, Liming, Hu, Nan, Miao, Xiaoping, Zhou, Yifeng, Liu, Zhihua, Zhan, Qimin, Liu, Yu, Qiao, Yan, Zhou, Yuling, Jin, Guangfu, Guo, Chuanhai, Lu, Changdong, Yang, Haijun, Fu, Jianhua, Yu, Dianke, Freedman, Neal D, Ding, Ti, Tan, Wen, Goldstein, Alisa M, Wu, Tangchun, Shen, Hongbing, Ke, Yang, Zeng, Yixin, Chanock, Stephen J, Taylor, Philip R, and Lin, Dongxin

Published
2014
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36. Genome wide analysis of DNA copy number neutral loss of heterozygosity (CNNLOH) and its relation to gene expression in esophageal squamous cell carcinoma

Author

Ding Ti, Taylor Philip R, Goldstein Alisa M, Wang Chaoyu, Yang Howard H, Clifford Robert J, Hu Nan, and Lee Maxwell P

Subjects
Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background Genomic instability plays an important role in human cancers. We previously characterized genomic instability in esophageal squamous cell carcinomas (ESCC) in terms of loss of heterozygosity (LOH) and copy number (CN) changes in tumors using the Affymetrix GeneChip Human Mapping 500K array in 30 cases from a high-risk region of China. In the current study we focused on copy number neutral (CN = 2) LOH (CNNLOH) and its relation to gene expression in ESCC. Results Overall we found that 70% of all LOH observed was CNNLOH. Ninety percent of ESCCs showed CNNLOH (median frequency in cases = 60%) and this was the most common type of LOH in two-thirds of cases. CNNLOH occurred on all 39 autosomal chromosome arms, with highest frequencies on 19p (100%), 5p (96%), 2p (95%), and 20q (95%). In contrast, LOH with CN loss represented 19% of all LOH, occurred in just half of ESCCs (median frequency in cases = 0%), and was most frequent on 3p (56%), 5q (47%), and 21q (41%). LOH with CN gain was 11% of all LOH, occurred in 93% of ESCCs (median frequency in cases = 13%), and was most common on 20p (82%), 8q (74%), and 3q (42%). To examine the effect of genomic instability on gene expression, we evaluated RNA profiles from 17 pairs of matched normal and tumor samples (a subset of the 30 ESCCs) using Affymetrix U133A 2.0 arrays. In CN neutral regions, expression of 168 genes (containing 1976 SNPs) differed significantly in tumors with LOH versus tumors without LOH, including 101 genes that were up-regulated and 67 that were down-regulated. Conclusion Our results indicate that CNNLOH has a profound impact on gene expression in ESCC, which in turn may affect tumor development.

Published
2010
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37. Family history of cancer and risk for esophageal and gastric cancer in Shanxi, China

Author

Goldstein Alisa, Ding Ti, Giffen Carol, Han XiaoYou, Hu Nan, Gao Ying, and Taylor Philip

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Family history (FH) by different relative types and risk of upper gastrointestinal (UGI) cancers has been only rarely reported; the data on UGI cancer survival are sparse. Methods 600 esophageal squamous cell carcinoma (ESCC) cases, 598 gastric cardia adenocarcinoma cases, and 316 gastric non-cardia adenocarcinoma cases, and 1514 age-, gender-, and neighborhood-matched controls were asked for FH in first degree relatives and non-blood relatives. Odds ratios (ORs) and 95% confidence intervals (CIs) from logistic regressions, and hazard ratios (HRs) from Cox proportional hazard regressions were estimated. Results Increased ESCC risk was associated with FH of any cancer (OR = 1.72, 95% CI = 1.39–2.12), FH of any UGI cancer (OR = 2.28, 95%CI = 1.77–2.95) and FH of esophageal cancer (OR = 2.84, 95%CI = 2.09–3.86), but not FH of non-UGI cancer. Individuals with two or more affected first-degree relatives had 10-fold increased ESCC risk. FH of gastric cardia cancer was associated with an increased risk of all three cancers. Cancer in non-blood relatives was not associated with risk of any UGI cancer. FH of UGI cancer was associated with a poorer survival rate among younger ESCC cases (HR = 1.82, 95%CI = 1.01–3.29). Conclusion These data provide strong evidence that shared susceptibility is involved in esophageal carcinogenesis and also suggest a role in prognosis.

Published
2009
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39. Genome-wide association studies of gastric adenocarcinoma and esophageal squamous cell carcinoma identify a shared susceptibility locus in PLCE1 at 10q23

Author

Abnet, Christian C, Freedman, Neal D, Hu, Nan, Wang, Zhaoming, Yu, Kai, Shu, Xiao-Ou, Yuan, Jian-Min, Zheng, Wei, Dawsey, Sanford M, Dong, Linda M, Lee, Maxwell P, Ding, Ti, Qiao, You-Lin, Gao, Yu-Tang, Koh, Woon-Puay, Xiang, Yong-Bing, Tang, Ze-Zhong, Fan, Jin-Hu, Wang, Chaoyu, Wheeler, William, Gail, Mitchell H, Yeager, Meredith, Yuenger, Jeff, Hutchinson, Amy, Jacobs, Kevin B, Giffen, Carol A, Burdett, Laurie, Jr, Joseph F Fraumeni, Tucker, Margaret A, Chow, Wong-Ho, Goldstein, Alisa M, Chanock, Stephen J, and Taylor, Philip R

Subjects
Male, Esophageal Neoplasms, Chromosomes, Human, Pair 10, Adenocarcinoma, digestive system diseases, Article, Linkage Disequilibrium, Phosphoinositide Phospholipase C, Asian People, Gene Frequency, Genetic Loci, Stomach Neoplasms, Case-Control Studies, Carcinoma, Squamous Cell, Humans, Female, Genetic Predisposition to Disease, Genome-Wide Association Study
Abstract

We conducted a genome-wide association study of gastric cancer and esophageal squamous cell carcinoma (ESCC) in ethnic Chinese subjects in which we genotyped 551,152 SNPs. We report a combined analysis of 2,240 gastric cancer cases, 2,115 ESCC cases and 3,302 controls drawn from five studies. In logistic regression models adjusted for age, sex and study, multiple variants at 10q23 had genome-wide significance for gastric cancer and ESCC independently. A notable signal was rs2274223, a nonsynonymous SNP located in PLCE1, for gastric cancer (P = 8.40 x 10(-9); per-allele odds ratio (OR) = 1.31) and ESCC (P = 3.85 x 10(-9); OR = 1.34). The association with gastric cancer differed by anatomic subsite. For tumors in the cardia the association was stronger (P = 4.19 x 10(-15); OR = 1.57), and for those in the noncardia stomach it was absent (P = 0.44; OR = 1.05). Our findings at 10q23 could provide insight into the high incidence of both cancers in China.

Published
2010

40. GWAS follow-up study of esophageal squamous cell carcinoma identifies potential genetic loci associated with family history of upper gastrointestinal cancer

Author

Song, Xin, primary, Li, Wen-Qing, additional, Hu, Nan, additional, Zhao, Xue Ke, additional, Wang, Zhaoming, additional, Hyland, Paula L., additional, Jiang, Tao, additional, Kong, Guo Qiang, additional, Su, Hua, additional, Wang, Chaoyu, additional, Wang, Lemin, additional, Sun, Li, additional, Fan, Zong Min, additional, Meng, Hui, additional, Zhang, Tang Juan, additional, Ji, Ling Fen, additional, Hu, Shou Jia, additional, Han, Wei Li, additional, Wu, Min Jie, additional, Zheng, Peng Yuan, additional, Lv, Shuang, additional, Li, Xue Min, additional, Zhou, Fu You, additional, Burdett, Laurie, additional, Ding, Ti, additional, Qiao, You-Lin, additional, Fan, Jin-Hu, additional, Han, Xiao-You, additional, Giffen, Carol, additional, Tucker, Margaret A., additional, Dawsey, Sanford M., additional, Freedman, Neal D., additional, Chanock, Stephen J., additional, Abnet, Christian C., additional, Taylor, Philip R., additional, Wang, Li-Dong, additional, and Goldstein, Alisa M., additional

Published
2017
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41. Abstract 3257: Molecular characterization of the human stomach microbiota in gastric cancer patients

Author

Yu, Guoqin, primary, Torres, Javier, additional, Hu, Nan, additional, Medrano-Guzman, Rafael, additional, Herrera-Goepfert, Roberto, additional, Humphrys, Michael S., additional, Wang, Lemin, additional, Wang, Chaoyu, additional, Ding, Ti, additional, Ravel, Jacques, additional, Taylor, Philip R., additional, Abnet, Christian, additional, and Goldstein, Alisa, additional

Published
2017
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42. Additional file 1: Figure S1. of Integrative genomics analysis of genes with biallelic loss and its relation to the expression of mRNA and micro-RNA in esophageal squamous cell carcinoma

Author

Hu, Nan, Chaoyu Wang, Clifford, Robert, Yang, Howard, Su, Hua, Lemin Wang, Wang, Yuan, Xu, Yi, Ze-Zhong Tang, Ding, Ti, Tongwu Zhang, Goldstein, Alisa, Giffen, Carol, Lee, Maxwell, and Taylor, Philip

Abstract

Flow diagram of laboratory analyses. (PPT 106 kb)

Published
2015
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43. 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

44. Incentive Mechanism for University Teachers under Multi-task Principal-Agent Model

Author

Lu Fang, Zhang Jiangshun, and Luo Ding Ti

Subjects
Microeconomics, Knowledge management, Incentive, Risk aversion, business.industry, Mechanism (biology), Remuneration, Principal–agent problem, Economics, Salary, Construct (philosophy), business, Task (project management)
Abstract

Currently universities have faced a popular realistic subject, that is, how to construct a reasonable salary incentive mechanism based on two tasks of teaching and scientific research for teachers. This paper builds a multi-task principal-agent model based on those tasks which are delegated to teachers by universities. Then, through in-depth analysis of the model, we explore the relationships among teachers' effort level, relative incentive intensity, tasks' uncertainty degree, and their risk aversion. The results show that, when teachers' risk aversion and tasks' uncertainty degree become bigger, their effort level will become lower. Secondly, the relative incentive intensity will reduce with the increase of the uncertainty of teaching task and the relative incentive intensity will increase with the increase of the uncertainty of scientific research task. Finally, teachers should be motivated differently according to tasks uncertainty and risk aversion.

Published
2014

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

Author

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

Abstract

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

Published
2014

46. Case-case comparison of smoking and alcohol risk associations with Epstein-Barr virus-positive gastric cancer: Behavioral Risk Factor in EBV-Positive Gastric Cancer

Author

Morgan, Douglas, Matsuo, Keitaro, Taylor, Philip, Camargo, M. Constanza, Hu, Nan, Alvarado-Cabrero, Isabel, Lissowska, Jolanta, Ding, Ti, Rabkin, Charles, Liao, Linda, Kim, Woo-Ho, Sung, Joseph, Torres, Javier, Meneses-Gonzalez, Fernando, Yu, Jun, Koriyama, Chihaya, Yatabe, Yashushi, Carrasquilla, Gabriel, Herrera-Goepfert, Roberto, Gulley, Margaret, and Akiba, Suminori

Subjects
hemic and lymphatic diseases
Abstract

Helicobacter pylori is the primary cause of gastric cancer. However, monoclonal Epstein-Barr virus (EBV) nucleic acid is also present in up to 10% of these tumors worldwide. EBV prevalence is increased with male sex, non-antral localization and surgically disrupted anatomy. To further examine associations between EBV and gastric cancer, we organized an international consortium of 11 studies with tumor EBV status assessed by in situ hybridization. We pooled individual-level data on 2,648 gastric cancer patients, including 184 (7%) with EBV-positive cancers; all studies had information on cigarette use (64% smokers) and 9 had data on alcohol (57% drinkers). We compared patients with EBV-positive and EBV-negative tumors to evaluate smoking and alcohol interactions with EBV status. To account for within-population clustering, multi-level logistic regression models were used to estimate interaction odds ratios (OR) adjusted for distributions of sex (72% male), age (mean 59 years), tumor histology (56% Lauren intestinal-type), anatomic subsite (61% noncardia) and year of diagnosis (1983–2012). In unadjusted analyses, the OR of EBV positivity with smoking was 2.2 (95% confidence interval [CI], 1.6–3.2). The OR was attenuated to 1.5 (95% CI, 1.01–2.3) by adjustment for the possible confounders. There was no significant interaction of EBV status with alcohol drinking (crude OR, 1.4; adjusted OR, 1.0). Our data indicate the smoking association with gastric cancer is stronger for EBV-positive than EBV-negative tumors. Conversely, the null association with alcohol does not vary by EBV status. Distinct epidemiologic characteristics of EBV-positive cancer further implicate the virus as a co-factor in gastric carcinogenesis.

Published
2014
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48. 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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49. Genomic Landscape of Somatic Alterations in Esophageal Squamous Cell Carcinoma and Gastric Cancer

Author

Hu, Nan, primary, Kadota, Mitsutaka, additional, Liu, Huaitian, additional, Abnet, Christian C., additional, Su, Hua, additional, Wu, Hailong, additional, Freedman, Neal D., additional, Yang, Howard H., additional, Wang, Chaoyu, additional, Yan, Chunhua, additional, Wang, Lemin, additional, Gere, Sheryl, additional, Hutchinson, Amy, additional, Song, Guohong, additional, Wang, Yuan, additional, Ding, Ti, additional, Qiao, You-Lin, additional, Koshiol, Jill, additional, Dawsey, Sanford M., additional, Giffen, Carol, additional, Goldstein, Alisa M., additional, Taylor, Philip R., additional, and Lee, Maxwell P., additional

Published
2016
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50. 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., Bou, Marta Crous, 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, III, 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., Carreon, 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., Jr., Freedman, Neal D., Fuchs, Charles S., Gao, Yu-Tang, Gapstur, Susan M., Patino-Garcia, Ana, Garcia-Closas, Montserrat, Gaziano, J. Michael, Giles, Graham G., Gillanders, Elizabeth M., Giovannucci, Edward L., Goldin, Lynn, Goldstein, Alisa M., Greene, Mark H., Hallmans, Göran, Harris, Curtis C., Henriksson, Roger, Holly, Elizabeth A., Hoover, Robert N., Hu, Nan, Hutchinson, Amy, Jenab, Mazda, Johansen, Christoffer, Khaw, Kay-Tee, Koh, Woon-Puay, Kolonel, Laurence N., Kooperberg, Charles, Krogh, Vittorio, Kurtz, Robert C., LaCroix, Andrea, Landgren, Annelie, Landi, Maria Teresa, Li, Donghui, Liao, Linda M., Malats, Nuria, McGlynn, Katherine A., McNeill, Lorna H., McWilliams, Robert R., Melin, Beatrice S., Mirabello, Lisa, Peplonska, Beata, Peters, Ulrike, Petersen, Gloria M., Prokunina-Olsson, Ludmila, Purdue, Mark, Qiao, You-Lin, Rabe, Kari G., Rajaraman, Preetha, Real, Francisco X., Riboli, Elio, Rodriguez-Santiago, Benjamin, Rothman, Nathaniel, Ruder, Avima M., Savage, Sharon A., Schwartz, Ann G., Schwartz, Kendra L., Sesso, Howard D., Severi, Gianluca, 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., Viswanathan, Kala, Wacholder, Sholom, Wang, Zhaoming, Weinstein, Stephanie J., Wheeler, William, White, Emily, Wiencke, John K., Wolpin, Brian M., Wu, Xifeng, Wunder, Jay S., Yu, Kai, Zanetti, Krista A., Zeleniuch-Jacquotte, Anne, Ziegler, Regina G., De Andrade, Mariza, Barnes, Kathleen C., Beaty, Terri H., Bierut, Laura J., Desch, Karl C., Doheny, Kimberly F., Feenstra, Bjarke, Ginsburg, David, Heit, John A., Kang, Jae H., Laurie, Cecilia A., Li, Jun Z., Lowe, William L., Marazita, Mary L., Melbye, Mads, Mirel, Daniel B., Murray, Jeffrey C., Nelson, Sarah C., Pasquale, Louis R., Rice, Kenneth, Wiggs, Janey L., Wise, Anastasia, Tucker, Margaret, Perez-Jurado, Luis A., Laurie, Cathy C., Caporaso, Neil E., Yeager, Meredith, Chanock, Stephen J., 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., Bou, Marta Crous, 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, III, 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., Carreon, 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., Jr., Freedman, Neal D., Fuchs, Charles S., Gao, Yu-Tang, Gapstur, Susan M., Patino-Garcia, Ana, Garcia-Closas, Montserrat, Gaziano, J. Michael, Giles, Graham G., Gillanders, Elizabeth M., Giovannucci, Edward L., Goldin, Lynn, Goldstein, Alisa M., Greene, Mark H., Hallmans, Göran, Harris, Curtis C., Henriksson, Roger, Holly, Elizabeth A., Hoover, Robert N., Hu, Nan, Hutchinson, Amy, Jenab, Mazda, Johansen, Christoffer, Khaw, Kay-Tee, Koh, Woon-Puay, Kolonel, Laurence N., Kooperberg, Charles, Krogh, Vittorio, Kurtz, Robert C., LaCroix, Andrea, Landgren, Annelie, Landi, Maria Teresa, Li, Donghui, Liao, Linda M., Malats, Nuria, McGlynn, Katherine A., McNeill, Lorna H., McWilliams, Robert R., Melin, Beatrice S., Mirabello, Lisa, Peplonska, Beata, Peters, Ulrike, Petersen, Gloria M., Prokunina-Olsson, Ludmila, Purdue, Mark, Qiao, You-Lin, Rabe, Kari G., Rajaraman, Preetha, Real, Francisco X., Riboli, Elio, Rodriguez-Santiago, Benjamin, Rothman, Nathaniel, Ruder, Avima M., Savage, Sharon A., Schwartz, Ann G., Schwartz, Kendra L., Sesso, Howard D., Severi, Gianluca, 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., Viswanathan, Kala, Wacholder, Sholom, Wang, Zhaoming, Weinstein, Stephanie J., Wheeler, William, White, Emily, Wiencke, John K., Wolpin, Brian M., Wu, Xifeng, Wunder, Jay S., Yu, Kai, Zanetti, Krista A., Zeleniuch-Jacquotte, Anne, Ziegler, Regina G., De Andrade, Mariza, Barnes, Kathleen C., Beaty, Terri H., Bierut, Laura J., Desch, Karl C., Doheny, Kimberly F., Feenstra, Bjarke, Ginsburg, David, Heit, John A., Kang, Jae H., Laurie, Cecilia A., Li, Jun Z., Lowe, William L., Marazita, Mary L., Melbye, Mads, Mirel, Daniel B., Murray, Jeffrey C., Nelson, Sarah C., Pasquale, Louis R., Rice, Kenneth, Wiggs, Janey L., Wise, Anastasia, Tucker, Margaret, Perez-Jurado, Luis A., Laurie, Cathy C., Caporaso, Neil E., Yeager, Meredith, and Chanock, Stephen J.

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 x 3 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
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