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

Abstract

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.

IL1B gene polymorphisms, age and the risk of non-small cell lung cancer in a Chinese population

“…In previous studies, it has been revealed that IL1B rs12621220G/A (-3893), rs1143623G/C (-1464), rs16944T/C (-511) and rs1143627C/T (-31) formed a risk haplotype (GGCT) associated with NSCLC in European populations [17]. Among these SNPs, only the last two SNPs have been studied in Chinese populations and the results are not consistent [21,22,30].…”

IL1RN (interleukin 1 receptor antagonist)

“…These data were confirmed in Chinese patients, with a decreased risk of 32% in patients with IL1RN*2 allele (Hu et al, 2006). On the other hand, Lim and cols, found a 5-fold-time increased risk in lung cancer in never-smokers patients with the IL1RN*2 (Lim et al, 2011), but these results are not consistent, since Hu and cols, found a reduced risk in non-smokers with squamous cell carcinoma (Hu et al, 2006).…”

Cyclooxygenase-2 (COX-2) gene polymorphism in patients withdifferentiated thyroid carcinomas in the Turkish population

“…However, Cox et al did not find an association between the COX-2-765 C allele and cancer risk (37). To date, a number of case-control studies have been conducted to evaluate the association between COX-2 T8473C polymorphism and susceptibility to lung cancer (38,39). However, a recent metaanalysis suggested that COX-2 T8473C polymorphism was not associated with lung cancer risk (40).…”