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Joint effect of peroxisome proliferator-activated receptor γ genetic polymorphisms and estrogen-related risk factors on breast cancer risk: results from a case–control study in Taiwan

  • Epidemiology
  • Published:
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Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) has been linked with possible antineoplastic effects in colorectal carcinogenesis. However, data for the possible link between PPARγ and breast cancer risk are sparse. We assessed the association of three polymorphisms in PPARγ (rs10865710 [C-681T], rs1805192 [Pro12Ala], and rs3856806 [C1431T]) with the risk of breast cancer in an ethnic Chinese female population in Taiwan. In addition, interactions with estrogen exposures were also explored. Genotypes for the PPARγ polymorphisms were determined on 291 incident breast cancer cases and 589 matched controls by fluorogenic 5′-nuclease assay. The at-risk haplotypes were defined according to the three polymorphisms in the following order: C-681T, Pro12Ala, and C1431T, which include CCT, GGT, and GGC. In addition, a critical period of estrogen exposure was estimated by the interval between age at menarche and age at first full-term pregnancy. Overall, there was no evidence of a significant impact of individual polymorphisms of PPARγ on breast cancer risk. However, the haplotype analysis revealed that women harboring at-risk haplotypes showed a significant 67% increase in breast cancer risk [adjusted odds ratio (OR) 1.67; 95% confidence interval (CI) 1.11–2.52]. Furthermore, there was a significant joint effect of estrogen exposure-related factors and at-risk haplotypes of PPARγ on breast cancer risk (adjusted OR 4.04; 95% CI 1.89–8.65), particularly in premenopausal women. The present study implicates a role for PPARγ in breast cancer risk. Mechanistic studies to fully elucidate the mechanisms underlying PPARγ’s effects should be pursued in future investigations.

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Abbreviations

BMI:

Body mass index

CI:

Confidence interval

ERE:

Estrogen response element

HWE:

Hardy–Weinberg equilibrium

FFTP:

First full-term pregnancy

OR:

Odds ratio

PPARγ:

Peroxisome proliferator-activated receptor γ

STAT5:

Signal transducer and activator of transcription 5

WC:

Waist circumference

WHR:

Waist-to-hip ratio

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Acknowledgments

This study was funded by the grants from National Science Council, Taiwan, Republic of China (NSC 97-2314-B-030-006-MY3). The authors are indebted to all participated women of this study, in particular those who took the effort to supply this study with a blood sample.

Conflict of interest

The authors declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Public Health, College of Medicine, Fu-Jen Catholic University, No. 510, Jhongjheng Road, Sinjhuang City, Taipei County 242, Taiwan, ROC

    Mei-Hsuan Wu, Wan-Yun Chou & Chien-An Sun

  2. Department of Surgery, Tri-Service General Hospital, Taipei, Taiwan

    Chi-Hong Chu & Jyh-Cherng Yu

  3. School of Public Health, National Defense Medical Center, Taipei, Taiwan

    Yu-Ching Chou

  4. Department of Health Business Administration, Meiho University, Pingtung, Taiwan

    Tsan Yang

  5. Department of Radiology, Tri-Service General Hospital, Taipei, Taiwan

    Giu-Cheng Hsu

  6. Department of Pathology, Tri-Service General Hospital, Taipei, Taiwan

    Cheng-Ping Yu

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  1. Mei-Hsuan Wu
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  2. Chi-Hong Chu
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  4. Wan-Yun Chou
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Correspondence to Chien-An Sun.

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Wu, MH., Chu, CH., Chou, YC. et al. Joint effect of peroxisome proliferator-activated receptor γ genetic polymorphisms and estrogen-related risk factors on breast cancer risk: results from a case–control study in Taiwan. Breast Cancer Res Treat 127, 777–784 (2011). https://doi.org/10.1007/s10549-010-1282-4

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  • DOI: https://doi.org/10.1007/s10549-010-1282-4

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