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Single and multigenic analysis of the association between variants in 12 steroid hormone metabolism genes and risk of prostate cancer.

Abstract
To estimate the prostate cancer risk conferred by individual single nucleotide polymorphisms (SNPs), SNP-SNP interactions, and/or cumulative SNP effects, we evaluated the association between prostate cancer risk and the genetic variants of 12 key genes within the steroid hormone pathway (CYP17, HSD17B3, ESR1, SRD5A2, HSD3B1, HSD3B2, CYP19, CYP1A1, CYP1B1, CYP3A4, CYP27B1, and CYP24A1). A total of 116 tagged SNPs covering the group of genes were analyzed in 2,452 samples (886 cases and 1,566 controls) in three ethnic/racial groups. Several SNPs within CYP19 were significantly associated with prostate cancer in all three ethnicities (P = 0.001-0.009). Genetic variants within HSD3B2 and CYP24A1 conferred increased risk of prostate cancer in non-Hispanic or Hispanic Caucasians. A significant gene-dosage effect for increasing numbers of potential high-risk genotypes was found in non-Hispanic and Hispanic Caucasians. Higher-order interactions showed a seven-SNP interaction involving HSD17B3, CYP19, and CYP24A1 in Hispanic Caucasians (P = 0.001). In African Americans, a 10-locus model, with SNPs located within SRD5A2, HSD17B3, CYP17, CYP27B1, CYP19, and CYP24A1, showed a significant interaction (P = 0.014). In non-Hispanic Caucasians, an interaction of four SNPs in HSD3B2, HSD17B3, and CYP19 was found (P < 0.001). These data are consistent with a polygenic model of prostate cancer, indicating that multiple interacting genes of the steroid hormone pathway confer increased risk of prostate cancer.
AuthorsJoke Beuten, Jonathan A L Gelfond, Jennifer L Franke, Korri S Weldon, Analisa C Crandall, Teresa L Johnson-Pais, Ian M Thompson, Robin J Leach
JournalCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 18 Issue 6 Pg. 1869-80 (Jun 2009) ISSN: 1538-7755 [Electronic] United States
PMID19505920 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Gonadal Steroid Hormones
Topics
  • Aged
  • Genetic Predisposition to Disease
  • Genotype
  • Gonadal Steroid Hormones (genetics, metabolism)
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prostatic Neoplasms (genetics)
  • Risk Factors

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