Genetic Susceptibility Factors on Genes Involved in the Steroid Hormone Biosynthesis Pathway and Progesterone Receptor for Gastric Cancer Risk

Abstract

<div><h3>Background</h3><p>The objective of the study was to investigate the role of genes (<em>HSD3B1</em>, <em>CYP17A1</em>, <em>CYP19A1</em>, <em>HSD17B2</em>, <em>HSD17B1</em>) involved in the steroid hormone biosynthesis pathway and progesterone receptor (<em>PGR</em>) in the etiology of gastric cancer in a population-based two-phase genetic association study.</p> <h3>Methods</h3><p>In the discovery phase, 108 candidate SNPs in the steroid hormone biosynthesis pathway related genes and <em>PGR</em> 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.</p> <h3>Results</h3><p>Of the 108 SNPs in steroid hormone biosynthesis pathway related genes and <em>PGR</em> analyzed in the discovery phase, 23 SNPs in <em>PGR</em> in the recessive model and 10 SNPs in <em>CYP19A1</em> in the recessive or additive models were significantly associated with increased gastric cancer risk (<em>p</em><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 <em>CYP19A1</em> 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 <em>PGR</em> SNPs were not statistically significantly associated with gastric cancer risk.</p> <h3>Conclusions</h3><p>Our findings suggest <em>CYP19A1</em> that codes <em>aromatase</em> may play an important role in the association of gastric cancer risk and be a genetic marker for gastric cancer susceptibility.</p> </div