Genetic Variants in Peroxisome Proliferator-activated Receptor-gamma Gene Are Associated with Risk of Lung Cancer in a Chinese Population

Accumulating evidence indicates that activation of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) dampens the inflammation cascade and inhibits tumor growth of the lung, suggesting that it has tumor suppressor functions. We performed a case-control study of 500 incident lung cancer cases and 517 age- and sex frequency-matched cancer-free controls in a Chinese population to investigate the role of 11 selected single nucleotide polymorphisms (SNPs) of PPAR-gamma in the etiology of lung cancer. We found that decreased lung cancer risk was statistically significantly associated with seven SNPs (P = 0.0004 for rs13073869 and 0.0130 for rs1899951 in a dominant model; P = 0.0310 for rs4135247 in a log-additive model; and P = 0.0468 for rs2972162, 0.0175 for rs709151, 0.0172 for rs11715541 and 0.0386 for rs1175543 in an overdominant model). Consistent with these results of single-locus analysis, both the haplotype and the diplotype analyses revealed a protective effect of the haplotype 'AGA' and 'AAA' of rs13073869, rs1899951 and rs4135247. Furthermore, we observed a statistically significant interaction between the rs1899951 and cigarette smoking. Our results indicate that PPAR-gamma polymorphisms and their interaction with smoking may contribute to the etiology of lung cancer. These findings need to be validated in larger, preferably population-based, studies including different ethnic groups.