Genetic polymorphisms in CYP17, CYP3A4, CYP19A1, SRD5A2, IGF-1, and IGFBP-3 and prostate cancer risk in African-American men: the Flint Men's Health Study.
BACKGROUND
Association studies have examined the significance of several candidate genes based on biological pathways relevant to prostate carcinogenesis, including both the androgen and insulin-like growth factor pathways. Clinical and epidemiologic evidence suggest that androgens, specifically testosterone and dihydrotestosterone (DHT) are important not only in normal prostate growth but in the pathogenesis of prostate cancer. Similarly, the insulin-like growth factor-1 (IGF-1) signaling pathway regulates both cellular proliferation and apoptosis. Therefore, genes involved in the biosynthesis, activation, metabolism and degradation of androgens and the stimulation of mitogenic and antiapoptotic activities of prostate epithelial cells represent important candidates for affecting the development and progression of prostate cancer.


METHODS
Using resources from the Flint Men's Health Study, a population-based case control study of African-American men aged 40-79, we evaluated the associations between selected single-nucleotide polymorphisms (SNPs) in the CYP17, CYP3A4, CYP19A1, SDR5A2, IGF1, and IGFBP3 genes and prostate cancer diagnosis in 473 men (131 prostate cancer cases and 342 disease-free controls).


RESULTS
We found a significant association between prostate cancer and selected CYP17 SNP genotypes, with the heterozygous genotype conferring decreased risk. Suggestive evidence for association between IGF1 SNPs and prostate cancer were also found. No significant associations were observed between SNPs in the other genes and prostate cancer.


CONCLUSIONS
These findings suggest that variation in or around CYP17 and/or IGF1 may be associated with prostate cancer development in the African-American population. Additional studies are needed to determine whether these polymorphisms are indeed associated with prostate cancer risk in African Americans.
Sarma
Aruna V
AV
Department of Urology, University of Michigan Medical School, Ann Arbor, Michigan, USA. asarma@umich.edu
Dunn
Rodney L
RL
Lange
Leslie A
LA
Ray
Anna
A
Wang
Yunfei
Y
Lange
Ethan M
EM
Cooney
Kathleen A
KA
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics*; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D016022:Case-Control Studies; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008824:Michigan; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*
D004273:DNA, Neoplasm; C515497:IGFBP3 protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D007527:Isoenzymes; D007334:Insulin-Like Growth Factor I; D003577:Cytochrome P-450 Enzyme System; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase