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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 ofPPARAhave been associated with cardiovascular disease, obesity and type II diabetes mellitus. Although no research to date has investigated the possible link betweenPPARAand breast cancer, the function of this gene suggests that it could play a role in breast cancer development. SixPPARApolymorphisms were evaluated in association with incident breast cancer in a population-based case–control study (n = 1073 cases andn = 1112 controls) using unconditional logistic and multilevel regression and haplotype-based analyses. The odds of breast cancer were doubled among women withPPARApolymorphism rs4253760 (odds ratio = 1.97 for rare versus common homozygote alleles; 95% confidence interval: 1.14, 3.43). This association remained constant with the inclusion of all interrogated polymorphisms studied in hierarchical models. No additive interactions with body mass index or weight gain were present, but there was some evidence of interaction betweenPPARAvariants and aspirin use, defined as use at least once per week for 6 months or longer. Fourteen haplotypes were imputed with frequencies &gt;1% among postmenopausal women, but no statistically significant differences in haplotype frequencies between cases and controls were evident. Our results are the first to evaluate the relationship betweenPPARAand breast cancer incidence and suggest that replication in an independent cohort is warranted.

carcinogenesis

Peroxisome proliferator-activated receptor-alpha (              PPARA              ) genetic polymorphisms and breast cancer risk: a Long Island ancillary study