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Pleiotropic analysis of cancer risk loci on esophageal adenocarcinoma risk.


ABSTRACT: BACKGROUND:Several cancer-associated loci identified from genome-wide association studies (GWAS) have been associated with risks of multiple cancer sites, suggesting pleiotropic effects. We investigated whether GWAS-identified risk variants for other common cancers are associated with risk of esophageal adenocarcinoma (EA) or its precursor, Barrett's esophagus. METHODS:We examined the associations between risks of EA and Barrett's esophagus and 387 SNPs that have been associated with risks of other cancers, by using genotype imputation data on 2,163 control participants and 3,885 (1,501 EA and 2,384 Barrett's esophagus) case patients from the Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study, and investigated effect modification by smoking history, body mass index (BMI), and reflux/heartburn. RESULTS:After correcting for multiple testing, none of the tested 387 SNPs were statistically significantly associated with risk of EA or Barrett's esophagus. No evidence of effect modification by smoking, BMI, or reflux/heartburn was observed. CONCLUSIONS:Genetic risk variants for common cancers identified from GWAS appear not to be associated with risks of EA or Barrett's esophagus. IMPACT:To our knowledge, this is the first investigation of pleiotropic genetic associations with risks of EA and Barrett's esophagus.

SUBMITTER: Lee E 

PROVIDER: S-EPMC4648999 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Pleiotropic analysis of cancer risk loci on esophageal adenocarcinoma risk.

Lee Eunjung E   Stram Daniel O DO   Ek Weronica E WE   Onstad Lynn E LE   MacGregor Stuart S   Gharahkhani Puya P   Ye Weimin W   Lagergren Jesper J   Shaheen Nicholas J NJ   Murray Liam J LJ   Hardie Laura J LJ   Gammon Marilie D MD   Chow Wong-Ho WH   Risch Harvey A HA   Corley Douglas A DA   Levine David M DM   Whiteman David C DC   Bernstein Leslie L   Bird Nigel C NC   Vaughan Thomas L TL   Wu Anna H AH  

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20150912 11


<h4>Background</h4>Several cancer-associated loci identified from genome-wide association studies (GWAS) have been associated with risks of multiple cancer sites, suggesting pleiotropic effects. We investigated whether GWAS-identified risk variants for other common cancers are associated with risk of esophageal adenocarcinoma (EA) or its precursor, Barrett's esophagus.<h4>Methods</h4>We examined the associations between risks of EA and Barrett's esophagus and 387 SNPs that have been associated w  ...[more]

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