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

Ying Yang; Rita V Burke; Christie Y Jeon; Shen-Chih Chang; Po-Yin Chang; Hal Morgenstern; Donald P Tashkin; Jenny Mao; Wendy Cozen; Thomas M Mack; Jianyu Rao; Zuo-Feng Zhang

doi:10.1016/j.lungcan.2014.06.014

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

Lung Cancer. 2014 Sep;85(3):449-56. doi: 10.1016/j.lungcan.2014.06.014. Epub 2014 Jun 27.

Authors

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

Affiliations

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.

Keywords: Lung cancer; Peroxisome proliferator-activated receptors; Single nucleotide polymorphism; Survival; Upper aero-digestive tract cancers.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Alleles
Female
Follow-Up Studies
Gene-Environment Interaction
Genotype
Head and Neck Neoplasms / diagnosis
Head and Neck Neoplasms / genetics*
Head and Neck Neoplasms / mortality*
Humans
Lung Neoplasms / diagnosis
Lung Neoplasms / genetics*
Lung Neoplasms / mortality*
Male
Middle Aged
Neoplasm Grading
Peroxisome Proliferator-Activated Receptors / genetics*
Polymorphism, Genetic*
Polymorphism, Single Nucleotide
Prognosis
Proportional Hazards Models
Risk Factors

Substances

Peroxisome Proliferator-Activated Receptors

Abstract

Publication types

MeSH terms

Substances

Grants and funding