Unal Esra, Aslan Ezgi Irmak, Ozturk Tulin, Kurnaz Gomleksiz Ozlem, Kucukhuseyin Ozlem, Tuzuner M Bora, Seyhan M Fatih, Ozturk Oguz, Yilmaz Aydogan Hulya
Department of Molecular Medicine, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Vakıf Gureba c. Çapa 34093, Istanbul, Turkey.
Department of Pathology, Istanbul University- Cerrahpasa Medical School, Istanbul, Turkey.
Biochem Genet. 2021 Dec;59(6):1413-1426. doi: 10.1007/s10528-021-10068-5. Epub 2021 Apr 24.
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, r: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.
乳腺癌（BC）在全球女性中发病率较高，该疾病的发病机制和病因尚未完全明确。过氧化物酶体增殖物激活受体γ（PPARγ）是一种在能量代谢和细胞分化中起重要作用的核激素受体，也被认为在癌症发展过程中具有一定作用。然而，关于PPARγ与癌症相关性的研究结果并不一致，因此需要进一步研究该转录因子对BC风险的影响。在这项病例对照研究中，我们检测了土耳其BC患者PPARγ基因的Pro12Ala-（rs1801282）和C161T-（rs3856806）多态性。通过聚合酶链反应和限制性片段长度多态性技术，对95例确诊为BC的女性患者及119例对照进行了PPARγ多态性基因分型。与Ala12等位基因和CC161基因型相比，ProPro基因型和T161等位基因分别与BC风险增加相关（p < 0.001）。多因素回归分析证实，ProPro基因型（p < 0.011）、T161等位基因（p < 0.001）、吸烟（p = 0.019）和高龄（>60岁）（p = 0.007）是乳腺癌的危险因素。我们还发现PPARγ基因的Pro12Ala和C161T多态性处于连锁不平衡状态（D'：0.511，r：0.099）。与保护性的Ala12-CC161单倍型相比，携带ProPro-T161风险型PPARγ单倍型与更高的BC风险相关（p < 0.01，OR：7.797，95%CI：3.521-17.263）。我们得出结论，PPARγ基因的Pro12Ala和C161T多态性与BC风险增加相关，且处于连锁不平衡状态的ProPro-T161风险型单倍型会增强这种影响。
