We read with great interest the article by Hao et al. [1], which examined the association between endothelial nitric oxide synthase (eNOS) G894T polymorphism and breast cancer risk with a meta-analysis. The results indicated that eNOS G894T polymorphism was associated with breast cancer (TT vs. GG: odds ratio (OR) = 1.22, 95% confidence interval (CI) = 1.02-1.44; recessive model: OR = 1.21, 95% CI = 1.02-1.42). However, another recent meta-analysis by Zintzaras et al. [2] suggested that there was non-significant association between eNOS G894T polymorphism and breast cancer (T vs. G: OR = 1.06, 95% CI = 0.97-1.16; recessive model: OR = 1.19, 95% CI 0.99-1.43).After carefully inspecting the two studies, it was noted that in the study by Hao et al. [1], there were two methodological issues which did influence the conclusion.First, they included three studies [3-5] which didn't investigate the association between eNOS G894T polymorphism and breast cancer. Actually, the two studies [3,4] examined the association between polymorphisms and breast cancer outcomes (such as recurrence and death, and so on). In addition, the study by Ahn et al.[5] explored the association between polymorphisms and acute radiotoxicity risk. Therefore, the three studies should be excluded in the final meta-analysis. Second, they included three studies [6-8] containing the overlapping data. As the study by Li et al. [8] was the recent one and had the largest sample size, so the study by Yang et al. [6] and Hong et al. [7] should be excluded.In addition, we further excluded one study [9] which deviated from Hardy-Weinberg equilibrium in controls and included one recent study by Zintzaras et al. [2], and re-assessed the association between eNOS G894T polymorphism and breast cancer under co-dominant model, dominant model and recessive model (Figs. 1, 2, 3, 4). The meta-analysis included six studies with 1,790 cases and 1,664 controls, and the results didn't support the conclusion that eNOS G894T polymorphism was significantly associated with breast cancer risk.
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