Opposite impact of NKG2D genotype by lifestyle exposure to risk of aerodigestive tract cancer among Japanese

Int J Cancer. 2008 Jul 1;123(1):181-6. doi: 10.1002/ijc.23456.


It was reported that there are 2 haplotypes in natural killer complex (NKC) region. One of them could be divided by NKG2D polymorphism into 2 haplotype alleles (high and low natural killer (NK) cell activity) and were associated with overall cancer risks. However, its impact on a specific cancer is unclear. Therefore, by a case-control study, we analyzed the association between NKG2D genotype and aerodigestive tract cancer risk. Subjects were 502 aerodigestive tract cancer patients (276 with head and neck, 226 with esophageal) and 1,004 sex-age matched noncancer controls. Exposures to 2 lifestyle factors, smoking and drinking, were evaluated by a self-administered questionnaire. The genotype of NKG2D was determined by the TaqMan method, and its impact was assessed by multivariable logistic regression models. Association strength was measured by the odds ratio (OR) and its confidence intervals (CI). An overall analysis revealed no statistically significant association between NKG2D genotype and the risk of aerodigestive tract cancer. However, we found protective effects of G allele among never smokers (OR 0.35; 95% CI 0.15-0.84) and never drinkers (0.42; 0.19-0.94). In contrary, increased risks were observed for G allele among heavy smokers (5.92; 3.23-10.85) and heavy drinkers (4.13; 2.29-7.47). Interactions between NKG2D genotype and lifestyle exposure were statistically significant (interaction p = 0.001 for smoking, 0.005 for drinking). The same trends were observed in both sexes, and in head and neck cancer and esophageal cancer independently. These results suggest an opposite impact of NKG2D genotype by lifestyle exposure to the risk of aerodigestive tract cancer among a Japanese population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alcohol Drinking / adverse effects*
  • Asian People / statistics & numerical data*
  • Case-Control Studies
  • Esophageal Neoplasms / epidemiology*
  • Esophageal Neoplasms / etiology
  • Esophageal Neoplasms / genetics*
  • Female
  • Genotype
  • Head and Neck Neoplasms / epidemiology*
  • Head and Neck Neoplasms / etiology
  • Head and Neck Neoplasms / genetics*
  • Humans
  • Life Style*
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • NK Cell Lectin-Like Receptor Subfamily K
  • Odds Ratio
  • Receptors, Immunologic / genetics*
  • Receptors, Natural Killer Cell
  • Respiratory Tract Neoplasms / epidemiology
  • Respiratory Tract Neoplasms / genetics
  • Risk Factors
  • Smoking / adverse effects*
  • Surveys and Questionnaires


  • KLRK1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell