Polymorphisms in genes in the androgen pathway and risk of Barrett's esophagus and esophageal adenocarcinoma
2016 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 138, no 5, 1146-1152 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2016. Vol. 138, no 5, 1146-1152 p.
genome-wide association study; Barrett esophagus; esophageal neoplasms; neoplasm; hormones; gonadal steroid hormone
Cancer and Oncology
IdentifiersURN: urn:nbn:se:uu:diva-273743DOI: 10.1002/ijc.29863ISI: 000369164700012PubMedID: 26414697OAI: oai:DiVA.org:uu-273743DiVA: diva2:901948
FunderNIH (National Institute of Health), R01CA136725Swedish Cancer Society, 4559-B01-01XAASwedish Cancer Society, 4758-B02-01XABNIH (National Institute of Health), P01CA091955; R01CA001833; R01CA072866; R01CA057947; R01CA059636; R01CA100264; P30CA016672; R01CA133996; P50CA093459; U01CA057949; U01CA057983; U01CA057923; R01DK63616Wellcome trust, 076113Wellcome trust, 090355