title: The steroid 5alpha-reductase type II TA repeat polymorphism is not associated with risk of breast or ovarian cancer in Australian women.
abstract: The enzyme 5alpha-reductase type II (SRD5A2) converts testosterone to its more active form 5alpha-dihydroxytestosterone. The 3' untranslated region of the gene contains a (TA)(n) length polymorphism. The (TA)(9) allele has been reported to be associated with higher serum prostate-specific antigen levels in breast tumors and lower risk of relapse in breast cancer patients and more recently has also been reported to be linked to the codon 89 valine variant, which is itself associated with higher serum prostate-specific antigen levels in breast tumors and a more favorable breast cancer prognosis. We investigated whether the SRD5A2 (TA)(n) polymorphism was associated with risk of breast or ovarian cancer in Australian women by studying 946 breast cancer cases and 509 age-matched controls, and 544 ovarian cancer cases and 298 controls of similar age distribution. The (TA)(9) allele frequency was similar in breast cancer cases (0.110), breast cancer controls (0.125), ovarian cancer cases (0.106), and ovarian cancer controls (0.117). There was no difference in genotype distribution between breast cancer cases and controls (P = 0.5), ovarian cancer cases and controls (P = 0.7), or between the two control groups (P = 0.9). Genotypes containing at least one (TA)(9) allele were not significantly associated with risk of breast cancer overall (odds ratio, 0.86; 95% confidence interval, 0.67-1.12; P = 0.3) or in women stratified by age, menopausal status, or family history. Similarly, the (TA)(9) allele was not associated with risk of ovarian cancer (odds ratio, 0.87; 95% confidence interval, 0.61-1.23; P = 0.4) or with ovarian tumor behavior (invasive or low malignant potential), histology, stage, or grade. Given that this study had sufficient power to detect altered risks in the order of 1.4- to 1.7-fold, our results suggest that the SRD5A2 (TA)(9) allele is unlikely to be associated with moderate alterations in breast or ovarian cancer risk.
authors.affiliation: Oncology Division, Joint Experimental Oncology Programme, The Queensland Institute of Medical Research, and The University of Queensland, Brisbane, QLD 4029 Australia.
authors.forename: A B
authors.initials: AB
authors.lastname: Spurdle
authors.forename: J L
authors.initials: JL
authors.lastname: Hopper
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: G S
authors.initials: GS
authors.lastname: Dite
authors.forename: M R
authors.initials: MR
authors.lastname: McCredie
authors.forename: G G
authors.initials: GG
authors.lastname: Giles
authors.forename: D J
authors.initials: DJ
authors.lastname: Venter
authors.forename: M C
authors.initials: MC
authors.lastname: Southey
authors.forename: D M
authors.initials: DM
authors.lastname: Purdie
authors.forename: G
authors.initials: G
authors.lastname: Chenevix-Trench
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics*; D000328:Adult; D000367:Age Factors; D001315:Australia / Q000453:epidemiology; D001943:Breast Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase