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Peroxisome Proliferator-Activated Receptor Gamma Pro12Ala/C161T Genotypes and Risky Haplotype Altering Risk of Breast Cancer: A Turkish Case–Control Study

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Abstract

Breast cancer (BC) has a high incidence rate among women worldwide, and the mechanisms and etiology of this disease are not yet fully understood. The peroxisome proliferator-activated receptor gamma (PPARgamma), a nuclear hormone receptor that plays important roles in energy metabolism and cellular differentiation, is also suggested to be effective in cancer development. However, the results of studies investigating the cancer association with PPARgamma are inconsistent, creating a need for further investigation of the effects of this transcription factor on BC risk. We have examined the Pro12Ala-(rs1801282) and C161T-(rs3856806) polymorphisms of the PPARgamma gene in Turkish patients with BC in this case–control study. A total of 95 women diagnosed with BC as cases and 119 controls were genotyped for PPARgamma polymorphisms by polymerase chain reaction and restriction fragment length polymorphism techniques. The ProPro genotype and T161 allele were associated with an increased risk of BC comparing with the Ala12 allele and CC161 genotype, respectively (p < 0.001). The multivariate regression analysis confirmed that the ProPro genotype (p < 0.011), T161 allele (p < 0.001), smoking (p = 0.019), and advanced age (> 60 years) (p = 0.007) are risk factors for breast cancer. We also found that the PPARgamma Pro12Ala and C161T polymorphisms were in linkage disequilibrium (D’:0.511, r2:0.099). It was determined that carrying ProPro-T161 risky PPARgamma haplotype was associated with a higher risk of BC compared to protective Ala12-CC161 haplotype (p < 0.01, OR:7.797, 95% CI:3.521–17.263). We concluded that PPARgamma Pro12Ala and C161T polymorphisms are associated with increased BC risk, and ProPro-T161 risky haplotype, which is in linkage disequilibrium, increases this effect.

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Data Availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

ATRA:

All-trans retinoic acid

CI:

Confidence interval

ER:

Estrogen receptor

HER-2 /neu :

Human epidermal growth factor receptor-2

HWE:

Hardy–Weinberg equilibrium

LD:

Linkage disequilibrium

OR:

Odds ratio

PPAR:

Peroxisome Proliferator-Activated Receptor

PCR:

Polymerase chain reaction

PR:

Progesterone receptor

RFLP:

Restriction fragment length polimorphism

RXR:

Retinoid X receptor

TGZ:

Troglitazone

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Funding

The present study was supported by a grant from the Scientific Research Projects Coordination Unit of Istanbul University (Project No:24082).

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Authors and Affiliations

  1. Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Vakıf Gureba c. Çapa 34093, Istanbul, Turkey

    Esra Unal, Ezgi Irmak Aslan, Ozlem Kucukhuseyin, Oguz Ozturk & Hulya Yilmaz Aydogan

  2. Department of Pathology, Istanbul University- Cerrahpasa Medical School, Istanbul, Turkey

    Tulin Ozturk

  3. Department of Medical Biology, School of Medicine, Istanbul Altinbas University, Istanbul, Turkey

    Ozlem Kurnaz Gomleksiz

  4. Research and Development Center, Acibadem Labmed Clinical Laboratories, Istanbul, Turkey

    M. Bora Tuzuner

  5. Department of Molecular Biology and Genetics, Faculty of Sciences and Literature, Yeni Yuzyil University, Istanbul, Turkey

    M. Fatih Seyhan

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  1. Esra Unal
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Correspondence to Hulya Yilmaz Aydogan.

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This study was in accordance with the Declaration of Helsinki for medical research involving human subjects. The protocol was approved by the Ethics Committee of the Istanbul University, Istanbul Faculty of Medicine (Approval number:2016/1287).

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Informed consent was obtained from all individual participants included in this study.

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Unal, E., Aslan, E.I., Ozturk, T. et al. Peroxisome Proliferator-Activated Receptor Gamma Pro12Ala/C161T Genotypes and Risky Haplotype Altering Risk of Breast Cancer: A Turkish Case–Control Study. Biochem Genet 59, 1413–1426 (2021). https://doi.org/10.1007/s10528-021-10068-5

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