Genetic variants of NQO1 gene increase bladder cancer risk in Indian population and meta-analysis

• Published in: Tumor biology 2014-07, Vol.35 (7), p.6415-6423
• Main Authors: Mandal, Raju K., Dubey, Sandhya, Panda, Aditya K., Mittal, Rama D.
• Format: Article
• Language: English
• Subjects: Asian Continental Ancestry Group; Biomedical and Life Sciences; Biomedicine; Bladder cancer; Cancer Research; Exons - genetics; Genetic Association Studies; Genetic Predisposition to Disease; Genotype & phenotype; Humans; Meta-analysis; NAD(P)H Dehydrogenase (Quinone) - genetics; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - pathology; Polymorphism, Single Nucleotide; Population genetics; Research Article; Risk Factors; Smoking - adverse effects; Smoking - pathology; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - pathology
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-014-1869-1

NAD(P)H: 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.