Role of NQO1 609C>T and NQO2 -3423G>A gene polymorphisms in esophageal cancer risk in Kashmir valley and meta analysis

Mol Biol Rep. 2012 Sep;39(9):9095-104. doi: 10.1007/s11033-012-1781-y. Epub 2012 Jun 27.

Abstract

Esophageal cancer (EC) is a complex multifactorial disorder, where environmental and genetic factors play major role. NADPH:quinone oxidoreductase 1 (NQO1) and NRH:quinone oxidoreductase 2 (NQO2) are phase II cytosolic enzymes that catalyze metabolism of quinones, important in the detoxification of environmental carcinogens. A case-control study was performed to investigated the associations of NQO1 609C>T and NQO2 -3423G>A polymorphisms with susceptibility to EC in a high-risk Kashmiri population of India in 135 EC patients and 195 unrelated healthy controls using PCR-RFLP. We also performed a meta analysis of nine published studies (1,224 cases and 1,740 controls) on NQO1 609C>T and evaluated the association between the NQO1 609C>T polymorphisms and esophageal cancer risk. A significant difference in NQO1 609C>T and NQO2 -3423G>A genotype distribution between EC cases and corresponding controls groups was observed (OR = 2.65; 95 % CI = 1.29-5.42 and OR = 1.88; 95 % CI = 1.02-3.49 respectively). Further, gene-gene interaction showed significantly increased risk for esophageal adenocarcinoma with variant genotypes of NQO1 609C>T and NQO2 -3423G>A polymorphisms and interaction with environmental risk factors revealed pronounced risk of EC with NQO1 609C>T TT genotype in high salted tea users of Kashmir valley (OR = 3.72, 95 % CI = 0.98-14.19). Meta analysis of NQO 609C>T polymorphism also suggested association of the polymorphism with EC in Asians as well as Europeans. In conclusion, NQO1 609C>T and NQO2 -3423G>A genetic variations modulate risk of EC in high-risk Kashmir population.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Asian People / genetics*
  • Case-Control Studies
  • Epistasis, Genetic
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • India
  • Male
  • Middle Aged
  • NAD(P)H Dehydrogenase (Quinone) / genetics*
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • Quinone Reductases / genetics
  • Risk*

Substances

  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, human
  • NRH - quinone oxidoreductase2
  • Quinone Reductases