Background:Evidence is increasingly emerging about multiple roles for the NAD(P)H quinone oxidoreductase 1 enzyme in cancer. The C609T (rs1800566, Pro187Ser) null polymorphism of the NQO1 gene contributes significantly to the variation in enzymatic activity across different populations. NQO1 C609T polymorphism was thoroughly investigated with respect to cancer susceptibility. The results were inconsistent partly due to low sample sizes. The aim of the present work was to perform a meta-analysis to assess association for all common cancer sites separately and in combination.Methods:Our meta-analysis involved 92 studies including 21 178 cases and 25 157 controls. Statistical analysis involved individual cancer sites and the combined cancer risk. Association was tested under different genetic models.Results:We found a statistically significant association between the variant T allele and overall cancer risk in the worldwide population (for the TT vs CC model, OR=1.18 (1.07–1.31), P=0.002, I2=36%). Stratified analysis revealed that this association was largely attributed to the Caucasian ethnicity (for the TT vs CC model, OR=1.28 (1.12–1.46), P=0.0002, I2=1%). Stratification by tumour site showed significant association for bladder cancer in the worldwide population (for the TT vs CC model, OR=1.70 (1.17–2.46), P=0.005, I2=0%), and in the Asian population (for the TT vs CC model, 1.48 (1.14–1.93), P=0.003, I2=16%). Positive association was also found for gastric cancer in the worldwide population under the dominant model (OR=1.34 (1.09–1.65), P=0.006, I2=15%).Conclusion:Our results indicate that the C609T polymorphism of the NQO1 gene is an important genetic risk factor in cancer.

Inspired by the reactivity of (per)chlorate reducing molybdoenzymes and encouraged by the lack of molybdenum-containing functional models thereof, two molybdenum(VI) complexes of the type [MoO 2 L 2 ] (L = pyrimidine-2-thiolate or 6methylpyridine-2-thiolate) were found to be active homogeneous catalysts for the reduction of ClO 4 − to ClO 3 − in CH 2 Cl 2 using PPh 3 as sacrificial oxygen acceptor. The subsequent stepwise reduction of ClO 3 − to Cl − is facilitated by our catalysts, but it can also proceed with only PPh 3 without the aid of a catalyst. We followed the decrease in perchlorate concentration in the catalytic solutions not only indirectly by oxidation of PPh 3 to OPPh 3 via 1 H NMR spectroscopy but also directly by determining the perchlorate concentration at certain time points over 24 h with high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICPMS/MS). These experiments revealed the pyrimidine-2-thiolate system to be more efficient. The reduction of ClO 4 − to ClO 3 − with [MoOL 2 ], which is generated after the reaction of [MoO 2 L 2 ] with PPh 3 , was computed to be highly exergonic with low kinetic barriers for both catalysts. Thus, the rate-determining step of the overall catalytic reaction is the initial oxygen atom transfer from [MoO 2 L 2 ] to PPh 3 .

Dietary folate status as well as polymorphisms in one-carbon metabolism genes may affect the risk of breast cancer through aberrant DNA methylation and altered nucleotide synthesis and DNA repair. A large number of studies investigated the role of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms in breast cancer with inconsistent results. Association between multiple polymorphisms in one-carbon metabolism genes and breast cancer was not studied before in an Arab population. The purpose of the present study is to test the hypothesis that polymorphisms in one-carbon metabolism genes are associated with breast cancer susceptibility in Syrian breast cancer women patients. A total of 245 subjects (119 breast cancer women patients and 126 healthy controls) were genotyped for MTHFR C677T and A1298C and MTRR A66G polymorphisms. Association was tested for under numerous genetic models. A statistically significant association was found for MTHFR A1298C polymorphism especially under the allele contrast model (odds ratio (OR) = 1.68, 95% confidence interval (CI) (1.16-2.45), P = 0.006). On the other hand, no significant association was found for MTHFR C677T or MTRR A66G under any of the genetic models tested. The effects of the compound genotypes were also examined. The 66GG genotype was found to be protective against breast cancer when combined with the 677CT or 1298AC genotype (OR = 0.18, 95% CI (0.04-0.82), P = 0.014; OR = 0.3, 95% CI (0.08-1.11), P = 0.058). In conclusion, our study supports the hypothesis that polymorphisms in one-carbon gene metabolisms modulate the risk for breast cancer, particularly the A1298C polymorphism of the MTHFR gene.

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