Pleiotropic analysis of cancer risk loci on esophageal adenocarcinoma

Cancer Epidemiology Biomarkers and Prevention. 2015 Sep 12. pii: cebp.0596.2015. [Epub ahead of print]

Pleiotropic analysis of cancer risk loci on esophageal adenocarcinoma risk.

Lee E, Stram D, Ek WE, Onstad LE, Macgregor S, Gharahkhani P, Ye W, Lagergren J, Shaheen NJ, Murray LJ, Hardie LJ, Gammon MD, Chow WH, Risch HA, Corley DA, Levine DM, Whiteman DC, Bernstein L, Vaughan TL, Wu A.



Anna Wu

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 (BE).

METHODS:  We examined the associations between risks of EA and BE and 387 single nucleotide polymorphisms (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 BE) 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 BE. 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 BE.

IMPACT:  To our knowledge, this is the first investigation of pleiotropic genetic associations with risks of EA and BE.

Copyright © 2015, American Association for Cancer Research.

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