Polymorphisms in inflammatory pathway genes, host factors and lung cancer risk in Chinese female never-smokers

Carcinogenesis. 2011 Apr;32(4):522-9. doi: 10.1093/carcin/bgr006. Epub 2011 Jan 20.


Inflammation appears to be important in lung carcinogenesis among smokers, but its role among never-smokers is not well established. We hypothesized that inflammatory medical conditions and gene polymorphisms interact to increase lung cancer risk in never-smokers. We interviewed 433 Singaporean female never-smoker lung cancer patients and 1375 hospital controls, and evaluated six polymorphisms in the interleukin 1-β, interleukin 6 (IL6), cyclooxygenase-2, peroxisome proliferator-activated receptor-γ and interleukin 1-β receptor antagonist (IL1RN) genes. Tuberculosis was associated with a non-significant elevated risk of lung cancer [odds ratio (OR) 1.58, 95% confidence interval (CI) 0.95-2.62]. There was no effect of asthma, atopy or chronic productive cough individually. However, the presence of one or more of these conditions (asthma, cough or atopy) increased risk (OR 2.24, 95%CI 1.15-4.38) in individuals possessing the T/T genotype at interleukin 1-β -31T/C, but not in those possessing the C/T (OR 0.87, 95%CI 0.51-1.57) or C/C genotypes (OR 0.58, 95%CI 0.27-1.27), and in individuals having the *2 variable number of tandem repeat allele of IL1RN [OR 5.09 (1.39-18.67)], but not in those without (OR 0.93, 95%CI 0.63-1.35). The IL6-634 G allele increased the risk of lung cancer (OR 1.44, 95%CI 1.07-1.94). Lung cancer risk also increased with the number of polymorphism sites where at least 1 'risk' allele was present [interleukin 1-β -31T/C (T allele), IL1RN (*2 allele) and IL6-634C/G (G allele)] among those with asthma, cough or atopy (Ptrend 0.001) but not in those without (Ptrend 0.47). Our results suggest that the effect of inflammatory medical conditions on lung cancer in never-smokers is modulated by host genetic susceptibility and will need to be confirmed in other studies conducted in similar populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • China
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / genetics
  • Interleukin-1beta / genetics
  • Interleukin-6 / genetics
  • Lung Neoplasms / etiology*
  • Lung Neoplasms / genetics
  • Middle Aged
  • Minisatellite Repeats
  • Polymorphism, Single Nucleotide*
  • Risk


  • IL1RN protein, human
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta
  • Interleukin-6