Genetic variants in sex hormone metabolic pathway genes and risk of esophageal squamous cell carcinoma

Paula L. Hyland, Neal D. Freedman, Nan Hu, Ze Zhong Tang, Lemin Wang, Chaoyu Wang, Ti Ding, Jin Hu Fan, You Lin Qiao, Asieh Golozar, William Wheeler, Kai Yu, Jeff Yuenger, Laurie Burdett, Stephen J. Chanock, Sanford M. Dawsey, Margaret A. Tucker, Alisa M. Goldstein, Christian C. Abnet, Philip R. Taylor

Research output: Contribution to journalArticlepeer-review

Abstract

In China, esophageal cancer is the fourth leading cause of cancer death where essentially all cases are histologically esophageal squamous cell carcinoma (ESCC), in contrast to esophageal ade-nocarcinoma in the West. Globally, ESCC is 2.4 times more common among men than women and recently it has been suggested that sex hormones may be associated with the risk of ESCC. We examined the association between genetic variants in sex hormone metabolic genes and ESCC risk in a population from north central China with high-incidence rates. A total of 1026 ESCC cases and 1452 controls were genotyped for 797 unique tag sin-gle-nucleotide polymorphisms (SNPs) in 51 sex hormone metabolic genes. SNP-, gene- and pathway-based associations with ESCC risk were evaluated using unconditional logistic regression adjusted for age, sex and geographical location and the adaptive rank truncated product (ARTP) method. Statistical significance was determined through use of permutation for pathway- and gene-based associations. No associations were observed for the overall sex hormone metabolic pathway (P = 0.14) or subpath-ways (androgen synthesis: P = 0.30, estrogen synthesis: P = 0.15 and estrogen removal: P = 0.19) with risk of ESCC. However, six individual genes (including SULT2B1, CYP1B1, CYP3A7, CYP3A5, SHBG and CYP11A1) were significantly associated with ESCC risk (P < 0.05). Our examination of genetic variation in the sex hormone metabolic pathway is consistent with a potential association with risk of ESCC. These positive findings warrant further evaluation in relation to ESCC risk and replication in other populations.

Original languageEnglish (US)
Pages (from-to)1062-1068
Number of pages7
JournalCarcinogenesis
Volume34
Issue number5
DOIs
StatePublished - May 2013

ASJC Scopus subject areas

  • Cancer Research

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