title: Genetic susceptibility factors on genes involved in the steroid hormone biosynthesis pathway and progesterone receptor for gastric cancer risk.
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.
authors.affiliation: Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Lisa Y
authors.initials: LY
authors.lastname: Cho
authors.forename: Jae Jeong
authors.initials: JJ
authors.lastname: Yang
authors.forename: Kwang-Pil
authors.initials: KP
authors.lastname: Ko
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Ma
authors.forename: Aesun
authors.initials: A
authors.lastname: Shin
authors.forename: Bo Youl
authors.initials: BY
authors.lastname: Choi
authors.forename: Dong Soo
authors.initials: DS
authors.lastname: Han
authors.forename: Kyu Sang
authors.initials: KS
authors.lastname: Song
authors.forename: Yong Sung
authors.initials: YS
authors.lastname: Kim
authors.forename: Soung-Hoon
authors.initials: SH
authors.lastname: Chang
authors.forename: Hai-Rim
authors.initials: HR
authors.lastname: Shin
authors.forename: Daehee
authors.initials: D
authors.lastname: Kang
authors.forename: Keun-Young
authors.initials: KY
authors.lastname: Yoo
authors.forename: Sue K
authors.initials: SK
authors.lastname: Park
mesh_terms: D000368:Aged; D001141:Aromatase / Q000235:genetics; D004960:Estradiol Dehydrogenases / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011375:Progesterone Reductase / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics*; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D013251:Steroid Isomerases / Q000235:genetics; D013274:Stomach Neoplasms / Q000209:etiology* / Q000235:genetics*
chemical_list: C021425:3 beta-hydroxysteroid oxidoreductase-delta(5) 3-ketosteroid isomerase; D009097:Multienzyme Complexes; D011980:Receptors, Progesterone; D011375:Progesterone Reductase; D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human; C523763:HSD17B2 protein, human; D001141:Aromatase; C561410:CYP19A1 protein, human; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; D013251:Steroid Isomerases