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

• We explore single nucleotide polymorphisms and cancer survival.
• Peroxisome proliferative activated receptor beta and delta are major interests.
• We apply semi-Bayesian shrinkage to adjust for potential false discoveries.
• Lung-cancer cases with the CC variant of rs3734254 may have a survival advantage.

BackgroundPeroxisome 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.Methods1212 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.ResultsThe 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).ConclusionOur 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.