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

Joke Beuten, Jonathan A Gelfond, Jennifer L. Franke, Korri S. Weldon, AnaLisa C. Crandall, Teresa L Johnson-pais, Ian M. Thompson, Robin J Leach

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1869-1880
Number of pages12
JournalCancer Epidemiology Biomarkers and Prevention
Volume18
Issue number6
DOIs
StatePublished - Jun 2009

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Single Nucleotide Polymorphism
Prostatic Neoplasms
Steroids
Hormones
Aromatase
Genes
25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Hispanic Americans
Steroid 17-alpha-Hydroxylase
Cytochrome P-450 CYP3A
Cytochrome P-450 CYP1A1
Gene Dosage
Ethnic Groups
African Americans
Genotype
Vitamin D3 24-Hydroxylase
3 beta-hydroxysteroid dehydrogenase type II

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Single and multigenic analysis of the association between variants in 12 steroid hormone metabolism genes and risk of prostate cancer. / Beuten, Joke; Gelfond, Jonathan A; Franke, Jennifer L.; Weldon, Korri S.; Crandall, AnaLisa C.; Johnson-pais, Teresa L; Thompson, Ian M.; Leach, Robin J.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 18, No. 6, 06.2009, p. 1869-1880.

Research output: Contribution to journalArticle

Beuten, Joke ; Gelfond, Jonathan A ; Franke, Jennifer L. ; Weldon, Korri S. ; Crandall, AnaLisa C. ; Johnson-pais, Teresa L ; Thompson, Ian M. ; Leach, Robin J. / Single and multigenic analysis of the association between variants in 12 steroid hormone metabolism genes and risk of prostate cancer. In: Cancer Epidemiology Biomarkers and Prevention. 2009 ; Vol. 18, No. 6. pp. 1869-1880.
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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.",
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AU - Franke, Jennifer L.

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AU - Crandall, AnaLisa C.

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