The NAD(P)H: Quinine Oxidoreductase 1 (NQO1) Gene 609 C>T Polymorphism is Associated with Gastric Cancer Risk: Evidence from a Case-control Study and a Meta-analysis

  • Hu, Wei-Guo (Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine) ;
  • Hu, Jia-Jia (Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine) ;
  • Cai, Wei (Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine) ;
  • Zheng, Min-Hua (Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine) ;
  • Zang, Lu (Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine) ;
  • Wang, Zheng-Ting (Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine) ;
  • Zhu, Zheng-Gang (Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine)
  • Published : 2014.03.01


The association between the NAD(P)H:quinone oxidoreductase 1 (NQO1) gene C609T polymorphism (rs1800566) and gastric cancer has been widely evaluated, but a definitive answer is so far lacking. We first conducted a case-control study to assess this association in a large Han Chinese population, and then performed a meta-analysis to further address this issue. Although our case-control association study indicated no significant difference in the genotype and allele distributions of C609T polymorphism between gastric cancer patients and controls, in the meta analysis involving 4,000 subjects, comparison of alleles 609T and 609C indicated a significantly increased risk (46%) for gastric cancer (95% confidence interval (95%CI) for odds ratio (OR)=1.20-1.79) in individuals with the T allele. The tendency was similar to the homozygote (OR=1.81, 95%CI: 1.16-2.84), dominant models (OR=1.41, 95%CI: 1.12-1.79), as well as recessive model (OR=1.58, 95%CI: 1.06-2.35). Stratified analysis by study design demonstrated stronger associations in population-based than in hospital-based studies. And ethnicity-based analysis demonstrated a significant association in Asians. We conclude that the NQO1 gene C609T polymorphism increases the risk for gastric cancer, especially in Asian populations.


  1. Zhang JH, Li Y, Wang R, et al (2003). NQO1 C609T polymorphism associated with esophageal cancer and gastric cardiac carcinoma in North China. World J Gastroenterol, 9, 1390-3.
  2. Zhu F, Loh M, Hill J, et al (2009). Genetic factors associated with intestinal metaplasia in a high risk Singapore-Chinese population: a cohort study. BMC Gastroenterol, 9, 76.
  3. Parkin DM, Bray F, Ferlay J, et al (2005). Global cancer statistics, 2002. CA. Cancer J Clin, 55, 74-108.
  4. Long DJ 2nd, Waikel RL, Wang XJ, et al (2000). NAD(P) H:quinone oxidoreductase 1 deficiency increases susceptibility to benzo(a)pyrene-induced mouse skin carcinogenesis. Cancer Res, 60, 5913-5.
  5. Long N, Moore MA, Chen W, et al (2010). Cancer epidemiology and control in north-East Asia - past, present and future. Asian Pac J Cancer Prev, 11, 107-48.
  6. Malik MA, Zargar SA, Mittal B (2011). Role of NQO1 609C>T and NQO2-3423G>A polymorphisms in susceptibility to gastric cancer in Kashmir valley. DNA Cell Biol, 30, 297-303.
  7. Rauth AM, Goldberg Z, Misra V (1997). DT-diaphorase: possible roles in cancer chemotherapy and carcinogenesis. Oncol Res, 9, 339-49.
  8. Ren JJ, Ouyang XH, Su XL (2006). NAD(P)H: quinone oxidoreductase gene polymorphism association with gastric carcinoma. Chin J Cancer Prev Treat, 13, 1686-8.
  9. Ruano-Ravina A, Perez-Rios M, Barros-Dios JM (2008). Population-based versus hospital-based controls: are they comparable? Gac Sanit, 22, 609-13.
  10. Salanti G, Sanderson S, Higgins JP (2005). Obstacles and opportunities in meta-analysis of genetic association studies. Genet Med, 7, 13-20. S
  11. Sarbia M, Bitzer M, Siegel D, et al (2003). Association between NAD(P)H: quinone oxidoreductase 1 (NQ01) inactivating C609T polymorphism and adenocarcinoma of the upper gastrointestinal tract. Int J Cancer, 107, 381-6.
  12. Wang Z, Hu J, Zhong J (2012). Meta-analysis of the NAD(P)H: quinine oxidoreductase 1 gene 609 C>T polymorphism with esophageal cancer risk. DNA Cell Biol, 31, 560-7.
  13. Guo ZJ, Feng CL (2012). The NQO1 rs1800566 polymorphism and risk of bladder cancer: evidence from 6,169 subjects. Asian Pac J Cancer Prev, 13, 6343-8.
  14. Chen DJ, Ding R, Ye DQ (2011). Interaction between polymorphisms in NQO1 (C609T) and XRCC1 (G28152A) and their correlation with smoking on gastric cancer. Zhonghua Liu Xing Bing Xue Za Zhi, 32, 5-8.
  15. Cohn LD, Becker BJ (2003). How meta-analysis increases statistical power. Psychol Methods, 8, 243-53.
  16. Goto Y, Hamajima N, Honda H, et al (2005). Association between Helicobacter pylori seropositivity and NAD(P) H:quinone oxidoreductase 1 (NQO1) C609T polymorphism observed in outpatients and health checkup examinees. Gastric Cancer, 8, 12-7.
  17. Han FF, Guo CL, Gong LL, et al (2013). Effects of the NQO1 609C>T polymorphism on leukemia susceptibility: evidence from a meta-analysis. Asian Pac J Cancer Prev, 14, 5311-6.
  18. Hamajima N, Matsuo K, Iwata H, et al (2002). NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T polymorphism and the risk of eight cancers for Japanese. Int J Clin Oncol, 7, 103-8.
  19. Hemminki K, Lorenzo Bermejo J, Forsti A (2006). The balance between heritable and environmental aetiology of human disease. Nat Rev Genet, 7, 958-65.
  20. Higgins JP, Thompson SG (2002). Quantifying heterogeneity in a meta-analysis. Stat Med, 21, 1539-58.
  21. Higgins JP, Thompson SG, Deeks JJ, et al (2003). Measuring inconsistency in meta-analyses. BMJ, 327, 557-60.
  22. Iskander K, Gaikwad A, Paquet M, et al (2005). Lower induction of p53 and decreased apoptosis in NQO1-null mice lead to increased sensitivity to chemical-induced skin carcinogenesis. Cancer Res, 65, 2054-8.
  23. Chen D, Chi Y, Yu Q, et al (2007). Interaction of polymorphisms of NQO1 and environmental risk factors in gastric cancer. Acta Universitatis Medicinalis Anhui, 42, 405-8.

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