The NQO1 Pro187Ser polymorphism and breast cancer susceptibility: evidence from an updated meta-analysis

Background: NAD(P)H: quinone oxidoreductase 1 (NQO1) plays a central role in catalyzing the two-electron reduction of quinoid compounds into hydroquinones. The NQO1 Pro187Ser polymorphism was found to correlate with a lower enzymatic activity, which may result in increased incidence of carcinomas including breast cancer. Previous studies investigating the association between NQO1 Pro187Ser polymorphism and breast cancer risk showed inconsistent results. We performed a meta-analysis to summarize the possible association. Methods: All studies published from January 1966 to February 2014 on the association between NQO1 Pro187Ser polymorphism and breast cancer risk were identified by searching electronic databases PubMed, EMBASE, Cochrane library, and Chinese Biomedical Literature database (CBM). The association between NQO1 Pro187Ser polymorphism and breast cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Results: Ten studies with 2,773 cases and 4,076 controls were finally included in the meta-analysis. We did not observe a significant association between NQO1 Pro187Ser polymorphism and breast cancer risk when all studies were pooled into the meta-analysis. In subgroup analysis by ethnicity, significant increased breast cancer risk was found in Caucasians (Ser/Pro vs. Pro/Pro: OR = 1.145, 95% CI = 1.008-1.301, P = 0.038; Ser/Ser + Ser/Pro vs. Pro/Pro: OR = 1.177, 95% CI = 1.041-1.331, P = 0.009). When stratified by source of control, significant increased breast cancer risk was found in population-based studies (Ser/Pro vs. Pro/Pro: OR = 1.180, 95% CI = 1.035-1.344, P = 0.013; Ser/Ser + Ser/Pro vs. Pro/Pro: OR = 1.191, 95% CI = 1.050-1.350, P = 0.007). However, in subgroup analyses according to menopausal status, quality score, and HWE in controls, no any significant association was detected. Conclusions: Our meta-analysis provides the evidence that the NQO1 Pro187Ser polymorphism contributed to the breast cancer susceptibility among Caucasians. Further large and well-designed studies are needed to confirm this association.