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

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 adenocarcinoma 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 single-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 subpathways (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.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Hyland PL,Freedman ND,Hu N,Tang ZZ,Wang L,Wang C,Ding T,Fan JH,Qiao YL,Golozar A,Wheeler W,Yu K,Yuenger J,Burdett L,Chanock SJ,Dawsey SM,Tucker MA,Goldstein AM,Abnet CC,Taylor PR

doi

10.1093/carcin/bgt030

subject

Has Abstract

pub_date

2013-05-01 00:00:00

pages

1062-8

issue

5

eissn

0143-3334

issn

1460-2180

pii

bgt030

journal_volume

34

pub_type

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