Androgen pathway genes and risk of Barrett’s and esophageal adenocarcinoma

Int J Cancer. 2015 Sep 28. doi: 10.1002/ijc.29863. [Epub ahead of print]

Published: Polymorphisms in genes in the androgen pathway and risk of Barrett’s esophagus and esophageal adenocarcinoma.

Ek WE1,2, Lagergren K3, Cook M4, Wu AH5, Abnet CC6, Levine D7, Chow WH8, Bernstein L9, Risch HA10, Shaheen NJ11, Bird NC12, Corley DA13, Hardie LJ14, Fitzgerald RC15, Gammon MD16, Romero Y17, Liu G18, Ye W19, Vaughan TL20, MacGregor S2, Whiteman DC21, Westberg L22, Lagergren J3,23.

 Abstract

lagergren

Jesper Lagergren

The strong male predominance in Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) remains inadequately explained, but sex hormones might be involved. We hypothesized that single nucleotide polymorphisms (SNPs) in the androgen pathway influence risk of developing BE and EAC. This genetic-epidemiological analysis included 14 studies from Australia, Europe and North America. Polymorphisms in 16 genes coding for the androgen pathway were analyzed using a gene-based approach: versatile gene-based test association study. This method evaluates associations between a trait and all SNPs within a specific gene rather than each SNP marker individually as in a conventional GWAS. The data were stratified for sex, body-mass index, waist-to-hip ratio, tobacco smoking and gastroesophageal reflux status. Included were data from 1,508 EAC patients, 2,383 BE patients and 2,170 control participants. SNPs within the gene CYP17A1 were associated with risk of BE in the sexes combined (p?=?0.002) and in males (p?=?0.003), but not in females separately (p?=?0.3). This association was found in tobacco smokers (p?=?0.003) and in BE patients without reflux (p?=?0.004), but not in nonsmokers (p?=?0.2) or those with reflux (p?=?0.036). SNPs within JMJD1C were associated with risk of EAC in females (p?=?0.001). However, none of these associations replicated in a subsequent sample. Fourteen other genes studied did not reach statistically significant levels of association with BE, EAC or the combination of BE and EAC, after correcting for the number of genes included in the analysis. In conclusion, genetic variants in the androgen-related genes CYP17A1 and JMJD1C might be associated with risk of BE and EAC, respectively, but replication data with larger sample sizes are needed.

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