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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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        Novel blood-based hypomethylation of SH3BP5 is associated with very early-stage lung adenocarcinoma

        Qiao Rong,Zhong Runbo,Liu Chunlan,Di Feifei,Zhang Zheng,Wang Ling,Xu Tian,Wang Yue,Dai Liping,Gu Wanjian,Han Baohui,Yang Rongxi 한국유전학회 2022 Genes & Genomics Vol.44 No.4

        Background: Early detection is essential to improve the survival of lung cancer (LC). The quantitative measurement of specific DNA methylation changes in the peripheral blood could provide an efficient strategy for the detection of early cancer. Objective: We applied a candidate approach and assess the association between blood-based SH3BP5 methylation and the risk of lung adenocarcinoma (LUAD) in a case-control cohort. Methods: The methylation level of four CpG sites in the promoter of SH3BP5 gene was quantitatively determined by mass spectrometry in 171 very early-stage LUAD patients (93.6% LUAD at stage I) and 190 age and gender-matched controls. The logistic regression and non-parametric tests were used for the statistical analyses. Results: We observed a significant association between decreased methylation of SH3BP5_CpG_4 in the peripheral blood and increased risk of LUAD (odds ratio (OR) per-10% methylation = 1.51, P = 0.006, FDR = 0.024), and even for the LUAD at stage I (OR per-10% methylation = 1.53, P = 0.006, FDR = 0.024). Moreover, the lower quartile of SH3BP5_CpG_4 methylation was correlated with increased risk for LUAD with a P trend of 0.011. Further investigation disclosed that the hypomethylation of SH3BP5_CpG_4 was mostly associated with LUAD in younger subjects (OR per-10% methylation = 2.02, P = 0.010, age < 55 years old) and probably could be enhanced by advance stage. Conclusion: Our study revealed an association between blood-based SH3BP5 hypomethylation and very early-stage LUAD, which provides a novel support for the blood-based methylation signatures as a potential marker for the evaluation of cancer risk.

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