The role of NQO1 polymorphisms in the susceptibility and chemotherapy response of Chinese NSCLC patients

Cell Biochem Biophys. 2014 Jul;69(3):475-9. doi: 10.1007/s12013-014-9820-z.

Abstract

To investigate whether the

Nad(p)h: quinone oxidoreductase 1 (NQO1) gene polymorphisms determine the Platinum-based chemotherapy in advanced non-small cell lung cancer (NSCLC) in a Chinese cohort. A total of 391 patients with inoperable advanced stage of NSCLC, namely, stage III (A + B) and IV NSCLC, and 663 age-and sex-matched healthy were enrolled. The effects of chemotherapy were evaluated. NQO1 C609T polymorphism was determined. The NSCLC patients had a significantly higher prevalence of TT than control subjects (33.76 vs. 21.67 %, P < 0.001). For allele comparison, NSCLC subjects had lower T allele frequency than controls as well (55.63 vs. 44.42 %, P < 0.001). multivariate regression analyses showed the TT carriage had a significantly increased risk for development of NSCLC after adjustments with age, sex, smoke, and cancer family history (OR 1.681, 95 % CI 1.242-2.274, P = 0.001). The TT genotype distribution was significantly higher in non-responders than in responders (31.85 vs. 21.96 %, P = 0.003). Logistic regression analysis showed TT genotype carriers had less chance to gain chemotherapy response compared to CC genotype carriers (OR 0.399, P = 0.003) after adjustment with sex, age, tumor histology, disease stage, and chemotherapy regimens. The NQO1 C609T polymorphism is an important molecular marker for advanced NSCLC, since it is associated with the NSCLC risk as well as the response status of platinum-based chemotherapy.

MeSH terms

  • Aged
  • Asian People / genetics
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Case-Control Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease / genetics*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / genetics*
  • Male
  • NAD(P)H Dehydrogenase (Quinone) / genetics*
  • Polymorphism, Single Nucleotide*
  • Treatment Outcome

Substances

  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, human