No association between androgen or vitamin D receptor gene polymorphisms and risk of breast cancer

Abstract

Endogenous hormone exposure is known to alter breast cancer susceptibility and genes responsive to such hormones are plausible candidates for predisposition genes. We have examined polymorphisms in genes for two members of the nuclear receptor superfamily which are expressed in breast tissue and known to moderate rates of cell proliferation in a case-control association study: the androgen receptor (AR) and the vitamin D receptor (VDR). We have used two series of Caucasian female breast cancer cases, one incident and one prevalent, and compared both with two sets of matched controls from the East Anglian region of Britain. Since the results are similar in the two series we have combined them. The AR poly[Gly](n) and poly[Gln](n) tracts were genotyped in a total of 508 female breast cancer cases and 426 controls. The VDR TaqI polymorphism was analysed in 951 cases and 627 controls drawn from the same population series. There were no significant differences between cases and controls for either the AR or VDR polymorphisms. Compared with individuals with two short alleles (<22 repeats) of the AR poly[Gln](n) tract, the odds ratios and 95% confidence intervals (95% CI) for individuals with one or two long alleles were 0.82 (95% CI 0.62-1.09) and 1.31 (95% CI 0.87-1.97), respectively. Heterozygotes and homozygotes for the VDR TaqI cutting site had odds ratios of 1.01 (95% CI 0.81-1.27) and 0.97 (95% CI 0.71-1.32), respectively. None of the AR or VDR polymorphisms investigated has a major effect on risk of breast cancer in the British population.

Androgen receptor (CAG)n polymorphisms and breast cancer risk in a Han Chinese population

“…When women from families with breast/ovarian cancer were examined in a case-only analysis, no association was found between (CAG)n repeat length and age at diagnosis or tumor type (Menin et al, 2001). A study of 508 patients and 426 controls from Britain showed no association (Dunning et al, 1999). Overall, we also did not observe any significant association between the CAG repeat polymorphism and BC risk.…”

Androgen receptor CAG repeat length in Jewish Israeli women who are BRCA1/2 mutation carriers: association with breast/ovarian cancer phenotype

“…The involvement of BRCA1 protein in steroid hormone regulation 11 combined with the putative role that the polymorphic CAG repeat (encod-ing for a polyglutamine tract) in exon 1 of the AR gene in prostate cancer 12 -14 contributed to the notion that AR gene may be involved in breast cancer pathogenesis. Direct analyses of the CAG repeat number in women diagnosed with breast cancer under 40 15 or 55 years of age, 16 did not demonstrate an association between age at disease diagnosis and CAG repeat size. Recently, a protective effect of having a short AR CAG repeat size allele was shown for Canadian incident breast cancer cases.…”

Polymorphisms in the vitamin D receptor and the androgen receptor gene associated with the risk of urolithiasis

“…The VDR and AR genes are both members of nuclear receptor superfamily regulating the genes for hormone-response (5). The transcriptional activity of the VDR gene is regulated in part by AR gene (6).…”