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Combined Effects of Peroxisome Proliferator–Activated Receptor Alpha and Apolipoprotein E Polymorphisms on Risk of Breast Cancer in a Taiwanese Population
  1. Chen Teng Wu, MD, MS*,
  2. Ya-Hsin Cheng, PhD,
  3. Fei-Na Chen, PhD,
  4. Dar-Ren Chen, MD§,
  5. Ming Feng Wei, MS,
  6. Nai-Wen Chang, PhD
  1. From the *Department of Surgery, Fong-Yuan Hospital, †Departments of Physiology and ‡Social Medicine, China Medical University; §Department of Surgery, Changhua Christian Hospital, Changhua; and ∥Department of Biochemistry, China Medical University, Taichung, Taiwan, ROC.
  1. Received June 1, 2012, and in revised form July 23, 2012.
  2. Accepted for publication July 24, 2012.
  3. Reprints: Nai-Wen Chang, PhD, Department of Biochemistry, College of Medicine, China Medical University, 91 Hsueh-Shih Rd, Taichung 404, Taiwan, ROC. E-mail: dnwchang{at}mail.cmu.edu.tw.
  4. Supported by research grants from the China Medical University (CMU100-TS-01) and the Taiwan Department of Health, China Medical University Hospital Cancer Research Center of Excellence (DOH101-TD-C-111-005).
  5. Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (www.jinvestigativemed.com).

Abstract

Background The peroxisome proliferator–activated receptor alpha (PPARA) and apolipoprotein E (APOE) proteins are reported to be correlated with lipid metabolism, cardiovascular disease, and breast cancer.

Methods We screened APOE and PPARA (S24F and V227A) polymorphisms in 306 breast cancer patients and 300 noncancer controls and determined the relationship between their genetic polymorphisms and breast cancer risk. Interactions with clinical characteristics were also examined.

Results We found that the risk of breast cancer was associated with APOE genotypes (P = 0.014) but not with PPARA S24F or V227A genotypes. The combined effects of F24/APOE genotypes (P = 0.003) on breast cancer risk were more significant than the individual effect of APOE genotypes (P = 0.014). F24/[Latin Small Letter Open E]4 carriers had a higher tendency to develop breast cancer than F24/[Latin Small Letter Open E]3 carriers (P = 0.013), and this effect is stronger than with individual [Latin Small Letter Open E]4 carriers (P = 0.029). In addition, both F24/[Latin Small Letter Open E]4 and V227/[Latin Small Letter Open E]4 carriers were significantly enriched in the human epidermal growth factor receptor 2/neu negative status.

Conclusions These findings suggest that the APOE [Latin Small Letter Open E]4 genotype plays a major role in the prediction of breast cancer, but the PPARA F24 mutation enhances this outcome. The combined effects of F24/[Latin Small Letter Open E]4 genotypes are positively associated with risk of breast cancer.

Key Words
  • PPAR alpha
  • Apolipoprotein E
  • genetic polymorphism
  • breast cancer

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