Ying Yang1, Rita V Burke2, Christie Y Jeon3, Shen-Chih Chang1, Po-Yin Chang4, Hal Morgenstern5, Donald P Tashkin6, Jenny Mao7, Wendy Cozen8, Thomas M Mack8, Jianyu Rao9, Zuo-Feng Zhang10. 1. Department of Epidemiology, University of California, Los Angeles (UCLA) School of Public Health, Los Angeles, CA, USA. 2. Pediatric Surgery, Children's Hospital Los Angeles, Los Angeles, CA, USA; Division of Pediatric Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA. 3. Cancer Prevention and Genetics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 4. Department of Epidemiology, University of California, Los Angeles (UCLA) School of Public Health, Los Angeles, CA, USA; Division of Endocrinology, Gerontology, & Metabolism, School of Medicine, Stanford University, Stanford, CA, USA; VA Palo Alto Health Care System, Palo Alto, CA, USA. 5. Departments of Epidemiology, Environmental Health Sciences, and Urology, Schools of Public Health and Medicine, and Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA. 6. Division of Pulmonary and Critical Care Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA, USA. 7. Pulmonary and Critical Care Section, New Mexico VA Healthcare System, Albuquerque, NM, USA. 8. Department of Preventive Medicine, USC Keck School of Medicine at University of Southern California, Los Angeles, CA, USA. 9. Department of Epidemiology, University of California, Los Angeles (UCLA) School of Public Health, Los Angeles, CA, USA; Department of Pathology, UCLA David Geffen School of Medicine, Los Angeles, CA, USA. 10. Department of Epidemiology, University of California, Los Angeles (UCLA) School of Public Health, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA. Electronic address: zfzhang@ucla.edu.
Abstract
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.
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 cancerpatients (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 PPARDrs3734254 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-cancerpatients with the CC variant of PPARDrs3734254 may have a survival advantage over lung-cancerpatients with other gene variants.
Authors: Heriberto Bruzzoni-Giovanelli; Juan R González; François Sigaux; Bruno O Villoutreix; Jean Michel Cayuela; Joëlle Guilhot; Claude Preudhomme; François Guilhot; Jean-Luc Poyet; Philippe Rousselot Journal: Oncotarget Date: 2015-11-03