Mandal Raju K, Dubey Sandhya, Panda Aditya K, Mittal Rama D
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014, Uttar Pradesh, India.
Tumour Biol. 2014 Jul;35(7):6415-23. doi: 10.1007/s13277-014-1869-1. Epub 2014 Mar 28.
quinone oxidoreductase (NQO1) is cytosolic enzymes that plays a role in protection against natural and xenobiotic quinones. This enzyme also protects cells from oxidative damage by preventing the generation of reactive oxygen species and reducing environmental carcinogens. The study included 200 bladder cancer (BC) patients and 200 healthy control individuals that had been matched by age and sex, and were of similar ethnicity. NQO1 Exon 4 (C > T) and Exon 6 (C > T) gene polymorphisms were genotyped by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP). We also performed a meta-analysis of 12 studies including the present study (2,286 cases and 2,294 controls) for NQO1 Exon 6 (C > T) polymorphism and overall BC susceptibility. Variant genotype TT of NQO1 Exon 6 (C > T) demonstrated a significant risk with BC (OR = 2.54; p = 0.016). T allele carriers (CT + TT) (OR = 1.60; p = 0.020) of NQO1 Exon 6, as well as T allele (OR = 1.60; p = 0.004) were at higher risk of BC. The diplotype C-T was observed to be associated with a significant increase BC risk (Bonferroni corrected p value, Pc = 0.02; OR = 1.61). In addition, a meta-analysis of the Exon 6 (C > T) polymorphism and BC risk showed that the variant of NQO1 Exon 6 genotypes was associated with an overall increased risk of BC, which was consistent with the results of the present study. However, none of these two polymorphisms were associated with tobacco smoking, tumor progression, and risk of BC recurrence in patients treated with BCG immunotherapy. Our results suggested that the NQO1 Exon 6 (C > T) may be associated with BC risk and could be a useful marker for primary prevention and development of BC in Indian population. Larger studies are required to validate these findings in diverse populations and of different ethnicities.
醌氧化还原酶（NQO1）是一种胞质酶，在抵御天然醌类和外源性醌类物质方面发挥作用。这种酶还通过防止活性氧的产生和还原环境致癌物来保护细胞免受氧化损伤。该研究纳入了200例膀胱癌（BC）患者和200名年龄、性别匹配且种族相似的健康对照个体。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对NQO1第4外显子（C>T）和第6外显子（C>T）基因多态性进行基因分型。我们还对包括本研究在内的12项研究（2286例病例和2294例对照）进行了荟萃分析，以探讨NQO1第6外显子（C>T）多态性与总体BC易感性的关系。NQO1第6外显子（C>T）的变异基因型TT显示出与BC显著相关的风险（OR=2.54；p=0.016）。NQO1第6外显子的T等位基因携带者（CT+TT）（OR=1.60；p=0.020）以及T等位基因（OR=1.60；p=0.004）患BC的风险更高。观察到双倍型C-T与BC风险的显著增加相关（经Bonferroni校正的p值，Pc=0.02；OR=1.61）。此外，对第6外显子（C>T）多态性与BC风险的荟萃分析表明，NQO1第6外显子基因型的变异与BC总体风险增加相关，这与本研究结果一致。然而，这两种多态性均与吸烟、肿瘤进展以及接受卡介苗免疫治疗的患者BC复发风险无关。我们的结果表明，NQO1第6外显子（C>T）可能与BC风险相关，并且可能是印度人群中BC一级预防和发病的有用标志物。需要更大规模的研究在不同人群和不同种族中验证这些发现。
