Peroxisome proliferator-activated receptor-alpha gene, obesity, and breast cancer incidence and survival: a LIBCSP ancillary study Public Deposited

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  • March 22, 2019
  • Golembesky, Amanda Keatley
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Peroxisome proliferator-activated receptor-alpha (PPARA) has been shown to increase fatty acid oxidation and decrease cytokine levels, and has been implicated in insulin production. Genetic variants of PPARA have been associated with cardiovascular disease, obesity and type II diabetes mellitus. Although no research to date has investigated the possible link between PPARA and breast cancer incidence and survival, the function of this gene suggests that it could play a role in breast cancer development and prognosis. Six PPARA polymorphisms were evaluated in association with incident breast cancer (n=1073 cases, n=1112 controls) and survival (n=1073 cases) in the Long Island Breast Cancer Study Project, a population-based case-control study. The National Death Index was used to determine vital status through December 31, 2002. The case-control study analyses used unconditional logistic and multilevel regression, and haplotype-based analyses while the survival analyses employed Kaplan-Meier curves, Cox regression and haplotype-based analyses for all-cause and breast cancer-specific mortality (n = 132 (12.3%) and 88 (8.2%), respectively). The odds of breast cancer were doubled among women with PPARA polymorphism rs4253760 (OR=1.97 for rare vs. common homozygote alleles; 95% CI: 1.14, 3.43). This association remained constant with the inclusion of all interrogated polymorphisms studied in hierarchical models. rs4253760 was also associated with over a two-fold increase in all-cause mortality at time of disease diagnosis with inclusion of a continuous time interaction (HR=2.25 for rare vs. common homozyote alleles; 95% CI: 1.00, 5.08). This beta coefficient for this time interaction is negative, implying that survival is improving over time, so that the HR is equal to 0.69 (95% CI: 0.36, 1.29) following five years of follow-up. Thus, caution is necessary when interpreting the results for this polymorphism. Haplotype analyses did not reveal any differences between cases and controls or survival. Our results are the first to evaluate the relationship between PPARA and breast cancer incidence and survival and suggest that replication in an independent cohort is warranted.
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  • Gammon, Marilie D.
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  • University of North Carolina at Chapel Hill
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