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


Unal E., Aslan E. I., ÖZTÜRK T., Kurnaz Gomleksiz O., KÜÇÜKHÜSEYİN Ö., Tuzuner M. B., ...Daha Fazla

Biochemical Genetics, cilt.59, sa.6, ss.1413-1426, 2021 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 59 Sayı: 6
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1007/s10528-021-10068-5
  • Dergi Adı: Biochemical Genetics
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.1413-1426
  • Anahtar Kelimeler: Breast cancer, C161T, PPARgamma, Pro12Ala, Single-nucleotide polymorphism
  • İstanbul Yeni Yüzyıl Üniversitesi Adresli: Evet

Özet

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.