STAT3 gene polymorphisms and susceptibility to non-small cell lung cancer.

Signal transducer and activator of transcription protein 3 (STAT3) has been implicated in cancer development and is recognized as a type of oncogene. However, association studies of single nucleotide polymorphisms (SNPs) in the STAT3 gene with cancer risk are rare and not available for lung cancer. We examined whether STAT3 polymorphisms are associated with the risk of non-small cell lung cancer (NSCLC). Eight SNPs in the STAT3 gene were genotyped by TaqMan assays in 326 NSCLC cases and 432 controls in a Chinese population. Significant decreased risk of NSCLC was observed for carriers of minor alleles rs4796793 (odds ratio (OR) = 0.68, 95% confidence interval (CI) = 0.51-0.92), rs7211777 (OR = 0.67, 95%CI = 0.50-0.90), rs12949918 (OR = 0.73, 95%CI = 0.54-0.97), rs744166 (OR = 0.69, 95%CI = 0.51-0.92), rs9912773 (OR = 0.75, 95%CI = 0.55-0.98), and rs3869550 (OR = 0.70, 95%CI = 0.53-0.94). The GGCGGC haplotype, comprised of minor alleles of the six NSCLC-associated SNPs, had a 0.78-fold (95%CI = 0.62-0.97) significantly decreased risk of NSCLC, as compared to the most common haplotype of CATACT. Stratification analyses by clinical stage showed that the trend for the association between STAT3 polymorphisms and NSCLC risk was present both for stage I/II and stage III/IV, and appeared moderately stronger for stage III/IV. We conclude that polymorphisms in the STAT3 gene may have a protective role in the development of NSCLC, particular of stage III/IV NSCLC.