Identifying susceptibility genes for prostate cancer--a family-based association study of polymorphisms in CYP17, CYP19, CYP11A1, and LH-beta.
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Douglas JA, Zuhlke KA, Beebe-Dimmer J, Levin AM, Gruber SB, Wood DP, Cooney KA
Identifying susceptibility genes for prostate cancer--a family-based association study of polymorphisms in CYP17, CYP19, CYP11A1, and LH-beta.
Cancer Epidemiol Biomarkers Prev. 2005 Aug;14(8):2035-9. doi: 10.1158/1055-9965.EPI-05-0170.
- PubMed ID
- 16103457 [ View in PubMed]
- Abstract
Polymorphisms in genes that code for enzymes or hormones involved in the synthesis and metabolism of androgens are compelling biological candidates for prostate cancer. Four such genes, CYP17, CYP19, CYP11A1, and LH-beta, are involved in the synthesis and conversion of testosterone to dihydrotestosterone and estradiol. In a study of 715 men with and without prostate cancer from 266 familial and early-onset prostate cancer families, we examined the association between prostate cancer susceptibility and common single-nucleotide polymorphisms in each of these four candidate genes. Family-based association tests revealed a significant association between prostate cancer and a common single-nucleotide polymorphism in CYP17 (P=0.004), with preferential transmission of the minor allele to unaffected men. Conditional logistic regression analysis of 461 discordant sibling pairs from these same families reaffirmed the association between the presence of the minor allele in CYP17 and prostate cancer risk (odds ratio, 0.51; 95% confidence interval, 0.28-0.92). These findings suggest that variation in or around CYP17 predicts susceptibility to prostate cancer. Family-based association tests may be especially valuable in studies of genetic variation and prostate cancer risk because this approach minimizes confounding due to population substructure, which is of particular concern for prostate cancer given the tremendous variation in the worldwide incidence of this disease.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Stanolone Cholesterol side-chain cleavage enzyme, mitochondrial Protein Humans UnknownSubstrateDetails Stanolone Cytochrome P450 19A1 Protein Humans UnknownSubstrateDetails