Polymorphisms of the endothelial nitric oxide synthase gene in breast cancer: a genetic association study and meta-analysis

The endothelial nitric oxide synthase gene (NOS3) has been proposed as a candidate gene for breast cancer (BC), however, the specific role of variants and haplotypes has not been clarified. We examined the association of two polymorphisms (4b/a and G894T) and their haplotypes in a case-control sample of 306 patients with BC and in 131 healthy females. In addition, a meta-analysis of studies investigating association between NOS3 polymorphisms and BC was conducted. The single locus analysis for the two polymorphisms revealed an association only for the 4b/a polymorphism, but adjustment for age diminished this association (odds ratio (OR) (95% confidence interval) 0.98 (0.34-2.81)). The analysis of haplotypes showed an association for two haplotypes involving the 894T allele (bT and aT) (P<0.05). The meta-analysis for both polymorphisms produced nonsignificant associations without significant heterogeneity. A positive association was detected for the promoter T786C polymorphism (pooled OR=1.51 (1.07-2.12)), but this comparison was based on few studies. The available evidence from our study and the meta-analysis cannot support a major contributory role of these common NOS3 polymorphisms in BC, although future larger studies may help in drawing safer conclusions about the genetics of BC. Journal of Human Genetics (2010) 55, 743-748; doi:10.1038/jhg.2010.100; published online 19 August 2010