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        RPTOR methylation in the peripheral blood and breast cancer in the Chinese population

        Yin Yifei,Lei Shuifang,Li Lixi,Yang Xiaoqin,Yin Qiming,Xu Tian,Zhou Wenjie,Li Hong,Gu Wanjian,Ma Fei,Yang Rongxi,Zhang Zhengdong 한국유전학회 2022 Genes & Genomics Vol.44 No.4

        Background: Altered regulatory-associated protein of mTOR, complex 1 (RPTOR) methylation levels in peripheral blood was originally discovered as breast cancer (BC)-associated risk factor in Caucasians. Objective: To explore the relationship between RPTOR methylation and BC in the Chinese population, we conducted two independent case-control studies. Methods: Peripheral blood samples were collected from a total of 333 sporadic BC cases and 378 healthy female controls for the DNA extraction and bisulfite-specific PCR amplification. Mass spectrometry was applied to quantitatively measure the levels of methylation. The logistic regression, Spearman's rank correlation, and Non-parametric tests were used for the statistical analyses. Results: In our study, we found an association between BC and RPTOR_CpG_4 hypomethylation in the general population (per-10% of methylation, OR 1.29, P = 0.012), and a weak association between BC and RPTOR_CpG_8 hypomethylation in the women with older age (per-10% of methylation, OR 2.34, P = 0.006). We also identified age as a confounder for the change of RPTOR methylation patterns, especially at RPTOR_CpG_4, which represented differential methylation comparing age groups especially in the BC cases (age < 50 years vs age ≥ 50 years by Mann-Whitney U test, P < 0.0001 for BC cases and P = 0.079 for controls). Conclusion: Our study validated the association between hypomethylation of RPTOR and BC risk in the Chinese population also with weak effect and mostly for postmenopausal women. In addition, our findings provided novel insight for the regulation of DNA methylation upon aging or the change of hormone levels.

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