Abstract
BackgroundNAD(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.MethodsAll 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).ResultsTen 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.ConclusionsOur 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.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1248639991252504
Highlights
NAD(P)H: quinone oxidoreductase 1 (NQO1) plays a central role in catalyzing the two-electron reduction of quinoid compounds into hydroquinones
In subgroup analysis by ethnicity, statistical significant increased breast cancer risk was found in Caucasians (Ser/Pro vs. Pro/Pro: odds ratio (OR) = 1.145, 95% confidence interval (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; Figure 1), but not in Asians and Arabs
The NQO1 Pro187Ser polymorphism was associated with an increased breast cancer risk among 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)
Summary
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. It was reported that the variant T allele was associated with reduced NQO1 enzymatic activity in both human cell lines and primary human tissues [9,10]. Given that the previous studies have consistently shown that the variant T allele resulted in reduced enzymatic activity, it was biologically reasonable to hypothesize a potential relationship between the NQO1 Pro187Ser polymorphism and cancer susceptibility
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