Genetic susceptibility factors on genes involved in the steroid hormone biosynthesis pathway and progesterone receptor for gastric cancer risk

PLoS One. 2012;7(10):e47603. doi: 10.1371/journal.pone.0047603. Epub 2012 Oct 23.

Abstract

Background: The objective of the study was to investigate the role of genes (HSD3B1, CYP17A1, CYP19A1, HSD17B2, HSD17B1) involved in the steroid hormone biosynthesis pathway and progesterone receptor (PGR) in the etiology of gastric cancer in a population-based two-phase genetic association study.

Methods: In the discovery phase, 108 candidate SNPs in the steroid hormone biosynthesis pathway related genes and PGR were analyzed in 76 gastric cancer cases and 322 controls in the Korean Multi-Center Cancer Cohort. Statistically significant SNPs identified in the discovery phase were re-evaluated in an extended set of 386 cases and 348 controls. Pooled- and meta-analyses were conducted to summarize the results.

Results: Of the 108 SNPs in steroid hormone biosynthesis pathway related genes and PGR analyzed in the discovery phase, 23 SNPs in PGR in the recessive model and 10 SNPs in CYP19A1 in the recessive or additive models were significantly associated with increased gastric cancer risk (p<0.05). The minor allele frequencies of the SNPs in both the discovery and extension phases were not statistically different. Pooled- and meta-analyses showed CYP19A1 rs1004982, rs16964228, and rs1902580 had an increased risk for gastric cancer (pooled OR [95% CI] = 1.22 [1.01-1.48], 1.31 [1.03-1.66], 3.03 [1.12-8.18], respectively). In contrast, all PGR SNPs were not statistically significantly associated with gastric cancer risk.

Conclusions: Our findings suggest CYP19A1 that codes aromatase may play an important role in the association of gastric cancer risk and be a genetic marker for gastric cancer susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aromatase / genetics
  • Estradiol Dehydrogenases / genetics
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Multienzyme Complexes / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Progesterone Reductase / genetics
  • Receptors, Progesterone / genetics*
  • Steroid 17-alpha-Hydroxylase / genetics
  • Steroid Isomerases / genetics
  • Stomach Neoplasms / etiology*
  • Stomach Neoplasms / genetics*

Substances

  • 3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase
  • Multienzyme Complexes
  • Receptors, Progesterone
  • Progesterone Reductase
  • Estradiol Dehydrogenases
  • HSD17B1 protein, human
  • HSD17B2 protein, human
  • Aromatase
  • CYP19A1 protein, human
  • CYP17A1 protein, human
  • Steroid 17-alpha-Hydroxylase
  • Steroid Isomerases

Grants and funding

This study was supported by a grant from (1) the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (0520140); (2) the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology [NRF-2009-353-0066258]; and (3) the Basic Research Laboratory (BRL) program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology [2011-0001564]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.