The CYP17 MspA1 polymorphism and breast cancer risk: a meta-analysis

Abstract

Inter-individual differences in susceptibility to breast cancer are partially mediated through the levels of endogenous and exogenous steroid hormones. The CYP17 gene encodes P450c17alpha, an enzyme that is involved in the metabolism of steroid hormones. Increased endogenous steroid hormone levels have been associated with a MspA1 polymorphism in the 5'-promoter region of the CYP17 gene. The CYP17 MspA1 polymorphism has been postulated as being associated with the risk of developing breast cancer. However, the association between the CYP17 MspA1 polymorphism and breast cancer risk has been controversial in the literature. To re-examine this controversy, we have undertaken a meta-analysis of 15 case-control studies, which included a total of 4227 breast cancer cases and 4730 individual controls. The odds ratio (OR) was used to evaluate the risk of breast cancer for each study, using homozygosity of the wild-type allele as the control group. Statistical analysis showed no evidence of heterogeneity within the studies. The pooled ORs of breast cancer associated with the combined variant (A1/A2 + A2/A2) and the homozygous genotype (A2/A2) were 0.98 (95% CI 0.89-1.07) and 1.05 (95% CI 0.87-1.21), respectively. Similarly, the pooled ORs of advanced breast cancer associated with the combined variant and the homozygous genotype were 0.96 (95% CI 0.77-1.20) and 0.88 (95% CI 0.55-1.41), respectively. A pooling of the studies was also conducted for the various ethnic groups, but failed to show an association of CYP17 MspA1 polymorphism with breast cancer risk in the different ethnic groups. In addition, our results show that a possible protective effect for breast cancer risk of a later age at menarche was mainly limited to women with the A1 homozygous genotype. The OR for age at menarche (> or = 13) was 0.87 (95% CI 0.62-1.17). Our results suggest that CYP17 MspA1 polymorphism may be at best a weak modifier of breast cancer risk but is not a significant independent risk factor.

Association of serum sex steroid levels and bone mineral density with CYP17 and CYP19 gene polymorphisms in postmenopausal women in Turkey

“…Of these two enzymes, CYP17 T to C polymorphic variant is implicated in osteoporotic predisposition. Most studies, however, could not establish a relationship between CYP17 TC polymorphism and circulating estrogen-androgen levels (Berstein et al, 2002;Feigelson et al, 2002;Kado et al, 2002;Ye and Parry, 2002;Somner et al, 2004). We also did not observe a statistically significant association between CYP17 TC polymorphism and sex steroid levels; however, there was a tendency of higher testosterone levels in osteoporotic patients compared to controls in the CYP17 TC genotype.…”

“…The CYP17 CC genotype was also found to show a very low frequency, probably because it is more pronounced in osteoporotic phenotypes as suggested by Somner et al (2004). CYP17 polymorphism could also play significant roles in testosterone synthesis, which functions in bone physiology, and therefore, it is possible that CYP17 is a strong candidate that functions in bone metabolism even though this gene has gender-specific effects on steroid metabolism (Zmuda et al, 2001;Ye and Parry, 2002;Sharp et al, 2004).…”

“…Loss of function mutations in the CYP17 gene results in reduced growth and osteoporosis. A common polymorphic variant in the CYP17 gene has recently been shown to be associated with femoral size and biologically available testosterone concentration in men (Ye and Parry, 2002;Sharp et al, 2004).…”

Genetic polymorphisms of estrogen metabolizing enzyme and breast cancer risk in Thai women

“…However, this hypothesis could not be verified experimentally in vitro by Kristensen et al 8 Although the rs743572 SNP has been postulated for an association with the risk of developing breast cancer, a metaanalysis of 15 case-control studies did not find any overall association. 9 The result of our study showed that the C allele is associated with an increased risk of breast cancer in premenopausal women (OR 5 1.65, 95% CI 1.03-2.64). Recently, Chakraborty et al 10 also found the T to C polymorphism in the CYP17 gene was associated with an early onset breast cancer risk.…”

Serum sex steroid hormone levels and polymorphisms of CYP17 and SRD5A2: implication for prostate cancer risk

“…18,19 So far, a few studies suggested that the A2 allele might increase the risk of breast cancer, while other studies suggested no such association. 20,21 On the other hand, in prostate cancer, the relation between the CYP17 polymorphism and prostate cancer risk has been conflicting. Although a few groups including ours reported that the A1 allele of CYP17 increased the risk of prostate cancer, other studies reported a negative association or converse results.…”