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.
Zintzaras
Elias
E
Department of Biomathematics, University of Thessaly School of Medicine, Larissa, Greece.
Grammatikou
Maria
M
Kitsios
Georgios D
GD
Doxani
Chrysa
C
Zdoukopoulos
Nikos
N
Papandreou
Christos
C
Patrikidou
Anna
A
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D055815:Young Adult
C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III