title: Polymorphisms of peroxisome proliferator-activated receptors and survival of lung cancer and upper aero-digestive tract cancers.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Epidemiology, University of California, Los Angeles (UCLA) School of Public Health, Los Angeles, CA, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Rita V
authors.initials: RV
authors.lastname: Burke
authors.affiliation: Cancer Prevention and Genetics, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Christie Y
authors.initials: CY
authors.lastname: Jeon
authors.affiliation: Department of Epidemiology, University of California, Los Angeles (UCLA) School of Public Health, Los Angeles, CA, USA.
authors.forename: Shen-Chih
authors.initials: SC
authors.lastname: Chang
authors.affiliation: 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.
authors.forename: Po-Yin
authors.initials: PY
authors.lastname: Chang
authors.affiliation: 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.
authors.forename: Hal
authors.initials: H
authors.lastname: Morgenstern
authors.affiliation: Division of Pulmonary and Critical Care Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA, USA.
authors.forename: Donald P
authors.initials: DP
authors.lastname: Tashkin
authors.affiliation: Pulmonary and Critical Care Section, New Mexico VA Healthcare System, Albuquerque, NM, USA.
authors.forename: Jenny
authors.initials: J
authors.lastname: Mao
authors.affiliation: Department of Preventive Medicine, USC Keck School of Medicine at University of Southern California, Los Angeles, CA, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Cozen
authors.affiliation: Department of Preventive Medicine, USC Keck School of Medicine at University of Southern California, Los Angeles, CA, USA.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Mack
authors.affiliation: 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.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Rao
authors.affiliation: 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.
authors.forename: Zuo-Feng
authors.initials: ZF
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D005260:Female; D005500:Follow-Up Studies; D059647:Gene-Environment Interaction; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors
chemical_list: D047492:Peroxisome Proliferator-Activated Receptors
keywords: Lung cancer; Peroxisome proliferator-activated receptors; Single nucleotide polymorphism; Survival; Upper aero-digestive tract cancers