Polymorphisms of peroxisome proliferator-activated receptors and survival of lung cancer and upper aero-digestive tract cancers.

Background: Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors involved in several biological processes such as inflammation, cancer growth, progression and apoptosis that are important in lung and upper aero-digestive tract (UADT) cancer outcomes. Nonetheless, there are no published studies of the relationship between PPARs gene polymorphisms and survival of patients with lung cancer or UADT cancers.

Methods: 1212 cancer patients (611 lung, 303 oral, 100 pharyngeal, 90 laryngeal, and 108 esophageal) were followed for a median duration of 11 years. We genotyped three potentially functional single nucleotide polymorphisms (SNPs) using Taqman - rs3734254 of the gene PPARD and rs10865710 and rs1801282 of the gene PPARG - and investigated their associations with lung and UADT cancer survival using Cox regression. A semi-Bayesian shrinkage approach was used to reduce the potential for false positive findings when examining multiple associations.

Results: The variant homozygote CC (vs. TT) of PPARD rs3734254 was inversely associated with mortality of both lung cancer (adjusted hazard ratio [aHR]=0.63, 95% confidence interval [CI]=0.42, 0.96) and UADT cancers (aHR=0.51, 95% CI=0.27, 0.99). Use of the semi-Bayesian shrinkage approach yielded a posterior aHR for lung cancer of 0.66 (95% posterior limits=0.44, 0.98) and a posterior aHR for UADT cancers of 0.58 (95% posterior limits=0.33, 1.03).

Conclusion: Our findings suggest that lung-cancer patients with the CC variant of PPARD rs3734254 may have a survival advantage over lung-cancer patients with other gene variants.