Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions
Dongxin Lin and colleagues report a genome-wide association study for esophageal squamous cell carcinoma (ESCC) in Chinese populations, identifying nine new susceptibility loci. They also perform a genome-wide gene-environment interaction analysis with alcohol consumption, a known risk factor for ES...
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| Veröffentlicht in: | Nature genetics 2012-10, Vol.44 (10), p.1090-1097 |
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| creator | 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 Lin, Dongxin |
| description | Dongxin Lin and colleagues report a genome-wide association study for esophageal squamous cell carcinoma (ESCC) in Chinese populations, identifying nine new susceptibility loci. They also perform a genome-wide gene-environment interaction analysis with alcohol consumption, a known risk factor for ESCC.
We conducted a genome-wide association study (GWAS) and a genome-wide gene-environment interaction analysis of esophageal squamous-cell carcinoma (ESCC) in 2,031 affected individuals (cases) and 2,044 controls with independent validation in 8,092 cases and 8,620 controls. We identified six new ESCC susceptibility loci, of which four, at chromosomes 4q23, 16q12.1, 22q12 and 3q27 had a significant marginal effect (
P
= 1.78 × 10
−39
to
P
= 2.49 × 10
−11
) and two of which, at 2q22 and 13q33, had a significant association only in the gene–alcohol drinking interaction (gene-environment interaction
P
(
P
G × E
) = 4.39 × 10
−11
and
P
G × E
= 4.80 × 10
−8
, respectively). Variants at the 4q23 locus, which includes the
ADH
cluster, each had a significant interaction with alcohol drinking in their association with ESCC risk (
P
G × E
= 2.54 × 10
−7
to
P
G × E
= 3.23 × 10
−2
). We confirmed the known association of the
ALDH2
locus on 12q24 to ESCC, and a joint analysis showed that drinkers with both of the
ADH1B
and
ALDH2
risk alleles had a fourfold increased risk for ESCC compared to drinkers without these risk alleles. Our results underscore the direct genetic contribution to ESCC risk, as well as the genetic contribution to ESCC through interaction with alcohol consumption. |
| doi_str_mv | 10.1038/ng.2411 |
| format | Article |
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We conducted a genome-wide association study (GWAS) and a genome-wide gene-environment interaction analysis of esophageal squamous-cell carcinoma (ESCC) in 2,031 affected individuals (cases) and 2,044 controls with independent validation in 8,092 cases and 8,620 controls. We identified six new ESCC susceptibility loci, of which four, at chromosomes 4q23, 16q12.1, 22q12 and 3q27 had a significant marginal effect (
P
= 1.78 × 10
−39
to
P
= 2.49 × 10
−11
) and two of which, at 2q22 and 13q33, had a significant association only in the gene–alcohol drinking interaction (gene-environment interaction
P
(
P
G × E
) = 4.39 × 10
−11
and
P
G × E
= 4.80 × 10
−8
, respectively). Variants at the 4q23 locus, which includes the
ADH
cluster, each had a significant interaction with alcohol drinking in their association with ESCC risk (
P
G × E
= 2.54 × 10
−7
to
P
G × E
= 3.23 × 10
−2
). We confirmed the known association of the
ALDH2
locus on 12q24 to ESCC, and a joint analysis showed that drinkers with both of the
ADH1B
and
ALDH2
risk alleles had a fourfold increased risk for ESCC compared to drinkers without these risk alleles. Our results underscore the direct genetic contribution to ESCC risk, as well as the genetic contribution to ESCC through interaction with alcohol consumption.</description><identifier>ISSN: 1061-4036</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/ng.2411</identifier><identifier>PMID: 22960999</identifier><identifier>CODEN: NGENEC</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/208/727/2000 ; 631/67/1504/1477 ; 692/699/67/2324 ; Adult ; Aged ; Agriculture ; Alcohol Dehydrogenase - genetics ; Alcohol Drinking - adverse effects ; Aldehyde Dehydrogenase - genetics ; Aldehyde Dehydrogenase, Mitochondrial ; Alleles ; Analysis ; Animal Genetics and Genomics ; Asian Continental Ancestry Group ; Biological and medical sciences ; Biomedicine ; Cancer genetics ; Cancer Research ; Carcinoma ; Carcinoma, Squamous Cell - etiology ; Carcinoma, Squamous Cell - genetics ; Case-Control Studies ; Chromosomes ; Development and progression ; Disease susceptibility ; Drinking (Alcoholic beverages) ; Environmental aspects ; Epidemiology ; Esophageal cancer ; Esophageal Neoplasms - etiology ; Esophageal Neoplasms - genetics ; Esophagus ; Female ; Fundamental and applied biological sciences. Psychology ; Gastroenterology. Liver. Pancreas. Abdomen ; Gene Function ; Gene loci ; Gene-Environment Interaction ; Genes ; Genetic aspects ; Genetic Loci ; Genetic Predisposition to Disease ; Genetic research ; Genetic susceptibility ; Genetics ; Genetics of eukaryotes. Biological and molecular evolution ; Genome-Wide Association Study ; Genomes ; Genomics ; Genotype-environment interactions ; Human Genetics ; Humans ; Male ; Medical sciences ; Middle Aged ; Physiological aspects ; Polymorphism, Single Nucleotide ; Recruitment ; Risk Factors ; Squamous cell carcinoma ; Studies ; Tumors</subject><ispartof>Nature genetics, 2012-10, Vol.44 (10), p.1090-1097</ispartof><rights>Springer Nature America, Inc. 2012</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2012 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Oct 2012</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c608t-2d072ab2e6867cc0c0059795d45ee820f5646677487231b0201bb227d2eef68a3</citedby><cites>FETCH-LOGICAL-c608t-2d072ab2e6867cc0c0059795d45ee820f5646677487231b0201bb227d2eef68a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/ng.2411$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/ng.2411$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=26418894$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22960999$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Chen</creatorcontrib><creatorcontrib>Kraft, Peter</creatorcontrib><creatorcontrib>Zhai, Kan</creatorcontrib><creatorcontrib>Chang, Jiang</creatorcontrib><creatorcontrib>Wang, Zhaoming</creatorcontrib><creatorcontrib>Li, Yun</creatorcontrib><creatorcontrib>Hu, Zhibin</creatorcontrib><creatorcontrib>He, Zhonghu</creatorcontrib><creatorcontrib>Jia, Weihua</creatorcontrib><creatorcontrib>Abnet, Christian C</creatorcontrib><creatorcontrib>Liang, Liming</creatorcontrib><creatorcontrib>Hu, Nan</creatorcontrib><creatorcontrib>Miao, Xiaoping</creatorcontrib><creatorcontrib>Zhou, Yifeng</creatorcontrib><creatorcontrib>Liu, Zhihua</creatorcontrib><creatorcontrib>Zhan, Qimin</creatorcontrib><creatorcontrib>Liu, Yu</creatorcontrib><creatorcontrib>Qiao, Yan</creatorcontrib><creatorcontrib>Zhou, Yuling</creatorcontrib><creatorcontrib>Jin, Guangfu</creatorcontrib><creatorcontrib>Guo, Chuanhai</creatorcontrib><creatorcontrib>Lu, Changdong</creatorcontrib><creatorcontrib>Yang, Haijun</creatorcontrib><creatorcontrib>Fu, Jianhua</creatorcontrib><creatorcontrib>Yu, Dianke</creatorcontrib><creatorcontrib>Freedman, Neal D</creatorcontrib><creatorcontrib>Ding, Ti</creatorcontrib><creatorcontrib>Tan, Wen</creatorcontrib><creatorcontrib>Goldstein, Alisa M</creatorcontrib><creatorcontrib>Wu, Tangchun</creatorcontrib><creatorcontrib>Shen, Hongbing</creatorcontrib><creatorcontrib>Ke, Yang</creatorcontrib><creatorcontrib>Zeng, Yixin</creatorcontrib><creatorcontrib>Chanock, Stephen J</creatorcontrib><creatorcontrib>Taylor, Philip R</creatorcontrib><creatorcontrib>Lin, Dongxin</creatorcontrib><title>Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><addtitle>Nat Genet</addtitle><description>Dongxin Lin and colleagues report a genome-wide association study for esophageal squamous cell carcinoma (ESCC) in Chinese populations, identifying nine new susceptibility loci. They also perform a genome-wide gene-environment interaction analysis with alcohol consumption, a known risk factor for ESCC.
We conducted a genome-wide association study (GWAS) and a genome-wide gene-environment interaction analysis of esophageal squamous-cell carcinoma (ESCC) in 2,031 affected individuals (cases) and 2,044 controls with independent validation in 8,092 cases and 8,620 controls. We identified six new ESCC susceptibility loci, of which four, at chromosomes 4q23, 16q12.1, 22q12 and 3q27 had a significant marginal effect (
P
= 1.78 × 10
−39
to
P
= 2.49 × 10
−11
) and two of which, at 2q22 and 13q33, had a significant association only in the gene–alcohol drinking interaction (gene-environment interaction
P
(
P
G × E
) = 4.39 × 10
−11
and
P
G × E
= 4.80 × 10
−8
, respectively). Variants at the 4q23 locus, which includes the
ADH
cluster, each had a significant interaction with alcohol drinking in their association with ESCC risk (
P
G × E
= 2.54 × 10
−7
to
P
G × E
= 3.23 × 10
−2
). We confirmed the known association of the
ALDH2
locus on 12q24 to ESCC, and a joint analysis showed that drinkers with both of the
ADH1B
and
ALDH2
risk alleles had a fourfold increased risk for ESCC compared to drinkers without these risk alleles. Our results underscore the direct genetic contribution to ESCC risk, as well as the genetic contribution to ESCC through interaction with alcohol consumption.</description><subject>631/208/727/2000</subject><subject>631/67/1504/1477</subject><subject>692/699/67/2324</subject><subject>Adult</subject><subject>Aged</subject><subject>Agriculture</subject><subject>Alcohol Dehydrogenase - genetics</subject><subject>Alcohol Drinking - adverse effects</subject><subject>Aldehyde Dehydrogenase - genetics</subject><subject>Aldehyde Dehydrogenase, Mitochondrial</subject><subject>Alleles</subject><subject>Analysis</subject><subject>Animal Genetics and Genomics</subject><subject>Asian Continental Ancestry Group</subject><subject>Biological and medical sciences</subject><subject>Biomedicine</subject><subject>Cancer genetics</subject><subject>Cancer Research</subject><subject>Carcinoma</subject><subject>Carcinoma, Squamous Cell - etiology</subject><subject>Carcinoma, Squamous Cell - genetics</subject><subject>Case-Control Studies</subject><subject>Chromosomes</subject><subject>Development and progression</subject><subject>Disease susceptibility</subject><subject>Drinking (Alcoholic beverages)</subject><subject>Environmental aspects</subject><subject>Epidemiology</subject><subject>Esophageal cancer</subject><subject>Esophageal Neoplasms - etiology</subject><subject>Esophageal Neoplasms - genetics</subject><subject>Esophagus</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gene Function</subject><subject>Gene loci</subject><subject>Gene-Environment Interaction</subject><subject>Genes</subject><subject>Genetic aspects</subject><subject>Genetic Loci</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic research</subject><subject>Genetic susceptibility</subject><subject>Genetics</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Genotype-environment interactions</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Physiological aspects</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Recruitment</subject><subject>Risk Factors</subject><subject>Squamous cell carcinoma</subject><subject>Studies</subject><subject>Tumors</subject><issn>1061-4036</issn><issn>1546-1718</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkt1u1DAQhSMEoqUg3gBZQhX0IovtOI59uVpBqVSpEn-3keNMUleJvc0kwD4Kb4ujLt0uQmLlC1v2N2c8ZyZJXjK6YDRT73y74IKxR8kxy4VMWcHU43imkqWCZvIoeYZ4QykTgqqnyRHnWlKt9XHy6xx86CH94WogBjFYZ0YXPDHedBsEJKEhgGF9bVowHcHbyfRhQmKh64g1g3Ux3hDnyeraeUAgUcmPrtmQfupGt-6A4IQW1qOrXOfGDelikqhfkxY8pOC_uyH4PgZFlREGY-cP4PPkSWM6hBfb_ST5-uH9l9XH9PLq_GK1vEytpGpMeU0LbioOUsnCWmopzXWh81rkAIrTJpdCyqIQquAZqyinrKo4L2oO0EhlspPk7Z3uegi3E-BY9g7n6oyHWGjJRCYolzzX_0epokplSsmIvv4LvQnTED2dKZ1LpXTOdlRrOiidb8IYy59Fy2VGhRZcijxSi39QcdXQOxs8NC7e7wWc7QVEZoSfY2smxPLi86dyKZniuWJMH8Aeqnv17XDdmX2o--aOtUNAHKAp14PrzbCJXpXzfJe-Lef5juSrra1T1UN9z_0Z6AicbgGD1nTNYLx1uOOkYNF6sWslxiffwvCwP_s5fwPfigwi</recordid><startdate>20121001</startdate><enddate>20121001</enddate><creator>Wu, Chen</creator><creator>Kraft, Peter</creator><creator>Zhai, Kan</creator><creator>Chang, Jiang</creator><creator>Wang, Zhaoming</creator><creator>Li, Yun</creator><creator>Hu, Zhibin</creator><creator>He, Zhonghu</creator><creator>Jia, Weihua</creator><creator>Abnet, Christian C</creator><creator>Liang, Liming</creator><creator>Hu, Nan</creator><creator>Miao, Xiaoping</creator><creator>Zhou, Yifeng</creator><creator>Liu, Zhihua</creator><creator>Zhan, Qimin</creator><creator>Liu, Yu</creator><creator>Qiao, Yan</creator><creator>Zhou, Yuling</creator><creator>Jin, Guangfu</creator><creator>Guo, Chuanhai</creator><creator>Lu, Changdong</creator><creator>Yang, Haijun</creator><creator>Fu, Jianhua</creator><creator>Yu, Dianke</creator><creator>Freedman, Neal D</creator><creator>Ding, Ti</creator><creator>Tan, Wen</creator><creator>Goldstein, Alisa M</creator><creator>Wu, Tangchun</creator><creator>Shen, Hongbing</creator><creator>Ke, Yang</creator><creator>Zeng, Yixin</creator><creator>Chanock, Stephen J</creator><creator>Taylor, Philip R</creator><creator>Lin, Dongxin</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>7U7</scope></search><sort><creationdate>20121001</creationdate><title>Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions</title><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 ; Lin, Dongxin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c608t-2d072ab2e6867cc0c0059795d45ee820f5646677487231b0201bb227d2eef68a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>631/208/727/2000</topic><topic>631/67/1504/1477</topic><topic>692/699/67/2324</topic><topic>Adult</topic><topic>Aged</topic><topic>Agriculture</topic><topic>Alcohol Dehydrogenase - genetics</topic><topic>Alcohol Drinking - adverse effects</topic><topic>Aldehyde Dehydrogenase - genetics</topic><topic>Aldehyde Dehydrogenase, Mitochondrial</topic><topic>Alleles</topic><topic>Analysis</topic><topic>Animal Genetics and Genomics</topic><topic>Asian Continental Ancestry Group</topic><topic>Biological and medical sciences</topic><topic>Biomedicine</topic><topic>Cancer genetics</topic><topic>Cancer Research</topic><topic>Carcinoma</topic><topic>Carcinoma, Squamous Cell - etiology</topic><topic>Carcinoma, Squamous Cell - genetics</topic><topic>Case-Control Studies</topic><topic>Chromosomes</topic><topic>Development and progression</topic><topic>Disease susceptibility</topic><topic>Drinking (Alcoholic beverages)</topic><topic>Environmental aspects</topic><topic>Epidemiology</topic><topic>Esophageal cancer</topic><topic>Esophageal Neoplasms - etiology</topic><topic>Esophageal Neoplasms - genetics</topic><topic>Esophagus</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gene Function</topic><topic>Gene loci</topic><topic>Gene-Environment Interaction</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Genetic Loci</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic research</topic><topic>Genetic susceptibility</topic><topic>Genetics</topic><topic>Genetics of eukaryotes. Biological and molecular evolution</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Genotype-environment interactions</topic><topic>Human Genetics</topic><topic>Humans</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Physiological aspects</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Recruitment</topic><topic>Risk Factors</topic><topic>Squamous cell carcinoma</topic><topic>Studies</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Chen</creatorcontrib><creatorcontrib>Kraft, Peter</creatorcontrib><creatorcontrib>Zhai, Kan</creatorcontrib><creatorcontrib>Chang, Jiang</creatorcontrib><creatorcontrib>Wang, Zhaoming</creatorcontrib><creatorcontrib>Li, Yun</creatorcontrib><creatorcontrib>Hu, Zhibin</creatorcontrib><creatorcontrib>He, Zhonghu</creatorcontrib><creatorcontrib>Jia, Weihua</creatorcontrib><creatorcontrib>Abnet, Christian C</creatorcontrib><creatorcontrib>Liang, Liming</creatorcontrib><creatorcontrib>Hu, Nan</creatorcontrib><creatorcontrib>Miao, Xiaoping</creatorcontrib><creatorcontrib>Zhou, Yifeng</creatorcontrib><creatorcontrib>Liu, Zhihua</creatorcontrib><creatorcontrib>Zhan, Qimin</creatorcontrib><creatorcontrib>Liu, Yu</creatorcontrib><creatorcontrib>Qiao, Yan</creatorcontrib><creatorcontrib>Zhou, Yuling</creatorcontrib><creatorcontrib>Jin, Guangfu</creatorcontrib><creatorcontrib>Guo, Chuanhai</creatorcontrib><creatorcontrib>Lu, Changdong</creatorcontrib><creatorcontrib>Yang, Haijun</creatorcontrib><creatorcontrib>Fu, Jianhua</creatorcontrib><creatorcontrib>Yu, Dianke</creatorcontrib><creatorcontrib>Freedman, Neal D</creatorcontrib><creatorcontrib>Ding, Ti</creatorcontrib><creatorcontrib>Tan, Wen</creatorcontrib><creatorcontrib>Goldstein, Alisa M</creatorcontrib><creatorcontrib>Wu, Tangchun</creatorcontrib><creatorcontrib>Shen, Hongbing</creatorcontrib><creatorcontrib>Ke, Yang</creatorcontrib><creatorcontrib>Zeng, Yixin</creatorcontrib><creatorcontrib>Chanock, Stephen J</creatorcontrib><creatorcontrib>Taylor, Philip R</creatorcontrib><creatorcontrib>Lin, Dongxin</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Toxicology Abstracts</collection><jtitle>Nature genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Chen</au><au>Kraft, Peter</au><au>Zhai, Kan</au><au>Chang, Jiang</au><au>Wang, Zhaoming</au><au>Li, Yun</au><au>Hu, Zhibin</au><au>He, Zhonghu</au><au>Jia, Weihua</au><au>Abnet, Christian C</au><au>Liang, Liming</au><au>Hu, Nan</au><au>Miao, Xiaoping</au><au>Zhou, Yifeng</au><au>Liu, Zhihua</au><au>Zhan, Qimin</au><au>Liu, Yu</au><au>Qiao, Yan</au><au>Zhou, Yuling</au><au>Jin, Guangfu</au><au>Guo, Chuanhai</au><au>Lu, Changdong</au><au>Yang, Haijun</au><au>Fu, Jianhua</au><au>Yu, Dianke</au><au>Freedman, Neal D</au><au>Ding, Ti</au><au>Tan, Wen</au><au>Goldstein, Alisa M</au><au>Wu, Tangchun</au><au>Shen, Hongbing</au><au>Ke, Yang</au><au>Zeng, Yixin</au><au>Chanock, Stephen J</au><au>Taylor, Philip R</au><au>Lin, Dongxin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions</atitle><jtitle>Nature genetics</jtitle><stitle>Nat Genet</stitle><addtitle>Nat Genet</addtitle><date>2012-10-01</date><risdate>2012</risdate><volume>44</volume><issue>10</issue><spage>1090</spage><epage>1097</epage><pages>1090-1097</pages><issn>1061-4036</issn><eissn>1546-1718</eissn><coden>NGENEC</coden><abstract>Dongxin Lin and colleagues report a genome-wide association study for esophageal squamous cell carcinoma (ESCC) in Chinese populations, identifying nine new susceptibility loci. They also perform a genome-wide gene-environment interaction analysis with alcohol consumption, a known risk factor for ESCC.
We conducted a genome-wide association study (GWAS) and a genome-wide gene-environment interaction analysis of esophageal squamous-cell carcinoma (ESCC) in 2,031 affected individuals (cases) and 2,044 controls with independent validation in 8,092 cases and 8,620 controls. We identified six new ESCC susceptibility loci, of which four, at chromosomes 4q23, 16q12.1, 22q12 and 3q27 had a significant marginal effect (
P
= 1.78 × 10
−39
to
P
= 2.49 × 10
−11
) and two of which, at 2q22 and 13q33, had a significant association only in the gene–alcohol drinking interaction (gene-environment interaction
P
(
P
G × E
) = 4.39 × 10
−11
and
P
G × E
= 4.80 × 10
−8
, respectively). Variants at the 4q23 locus, which includes the
ADH
cluster, each had a significant interaction with alcohol drinking in their association with ESCC risk (
P
G × E
= 2.54 × 10
−7
to
P
G × E
= 3.23 × 10
−2
). We confirmed the known association of the
ALDH2
locus on 12q24 to ESCC, and a joint analysis showed that drinkers with both of the
ADH1B
and
ALDH2
risk alleles had a fourfold increased risk for ESCC compared to drinkers without these risk alleles. Our results underscore the direct genetic contribution to ESCC risk, as well as the genetic contribution to ESCC through interaction with alcohol consumption.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>22960999</pmid><doi>10.1038/ng.2411</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1061-4036 |
| ispartof | Nature genetics, 2012-10, Vol.44 (10), p.1090-1097 |
| issn | 1061-4036 1546-1718 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1434026259 |
| source | MEDLINE; SpringerLink Journals; Nature Journals Online |
| subjects | 631/208/727/2000 631/67/1504/1477 692/699/67/2324 Adult Aged Agriculture Alcohol Dehydrogenase - genetics Alcohol Drinking - adverse effects Aldehyde Dehydrogenase - genetics Aldehyde Dehydrogenase, Mitochondrial Alleles Analysis Animal Genetics and Genomics Asian Continental Ancestry Group Biological and medical sciences Biomedicine Cancer genetics Cancer Research Carcinoma Carcinoma, Squamous Cell - etiology Carcinoma, Squamous Cell - genetics Case-Control Studies Chromosomes Development and progression Disease susceptibility Drinking (Alcoholic beverages) Environmental aspects Epidemiology Esophageal cancer Esophageal Neoplasms - etiology Esophageal Neoplasms - genetics Esophagus Female Fundamental and applied biological sciences. Psychology Gastroenterology. Liver. Pancreas. Abdomen Gene Function Gene loci Gene-Environment Interaction Genes Genetic aspects Genetic Loci Genetic Predisposition to Disease Genetic research Genetic susceptibility Genetics Genetics of eukaryotes. Biological and molecular evolution Genome-Wide Association Study Genomes Genomics Genotype-environment interactions Human Genetics Humans Male Medical sciences Middle Aged Physiological aspects Polymorphism, Single Nucleotide Recruitment Risk Factors Squamous cell carcinoma Studies Tumors |
| title | Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions |
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