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

ABSTRACT: 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, the function of this gene suggests that it could play a role in breast cancer development. Six PPARA polymorphisms were evaluated in association with incident breast cancer in a population-based case-control study (n = 1073 cases and n = 1112 controls) using unconditional logistic and multilevel regression and haplotype-based analyses. The odds of breast cancer were doubled among women with PPARA polymorphism 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 between PPARA variants and aspirin use, defined as use at least once per week for 6 months or longer. Fourteen haplotypes were imputed with frequencies >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 between PPARA and breast cancer incidence and suggest that replication in an independent cohort is warranted.

SUBMITTER: Golembesky AK

PROVIDER: S-EPMC2722854 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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

Golembesky Amanda K AK Gammon Marilie D MD North Kari E KE Bensen Jeannette T JT Schroeder Jane C JC Teitelbaum Susan L SL Neugut Alfred I AI Santella Regina M RM

Carcinogenesis 20080626 10

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, the function of this gene suggests that it could play a role in breast cancer development. Six PPARA polymo ...[more]

PMID: 18586686

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Project description:Peroxisome proliferator-activated receptors (PPARs) have unique functions in energy metabolism regulation but are also involved in regulation of the inflammatory process and obesity. The aim of this study was to analyse potential associations between polymorphisms of PPARA (rs1800206), PPARD (rs1053049; rs2267668) and PPARG (rs1801282) and overweight parameters. One hundred and sixty-six males, unrelated Caucasian military professionals, were recruited in the genetic case-control study conducted in the period 2016-2019. All the participants were aged 21-41 and had similar levels of physical activity. Body mass, height and body composition were measured. The participants were divided into two groups depending on their BMI (body mass index) and FMI (fat mass index). The control group consisted of people with BMI between 20.0 and 25.0 or FMI values ≤ 6, while the overweight group consisted of people with BMI of ≥ 25.0 or FMI values > 6. Genomic DNA was isolated from extracted buccal cells. All samples were genotyped using real-time polymerase chain reaction (real-time PCR). It was found that two polymorphisms rs2267668 and rs1053049 of the PPARD gene were significantly associated with BMI: SNP rs2267668 for the dominant (OR = 2.04, 95%CI 1.01-4.11, p-value = 0.04) model (A/G-G/G vs A/A). The likelihood of being overweight was over 2 times smaller for allele A. A relationship between the polymorphism of PPARG (rs1801282) and BMI was found for the overdominant (OR = 2.03, 95%CI 1.03-4.00, p-value = 0.04) model (C/G vs C/C-G/G). Significant associations were found in different models for PPARD, PPARG and PPARA genes with BMI. In SNP rs2267668 for the codominant genetic model (G/G vs A/A) (p-value = 0.04) and in SNP rs1053049 for the codominant (C/C vs T/T) (p-value = 0.01) and the recessive genetic model (C/C vs T/T-C/T) (p-value = 0.004) all polymorphisms were associated with BMI. In conclusion, it was found that three of the four polymorphisms (rs1053049, rs2267668, rs1801282) selected are associated with the risk of being overweight. Having said that, one has to bear in mind that DNA variants do not fully explain the reasons for being overweight. Therefore more research is needed to make a thorough assessment using the latest genomic methods in sequencing and genotyping, combined with epigenomics, proteomics, transcriptomics, and metabolomics.

Dataset Information

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

Publications

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

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