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

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Abstract

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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Availability of data and materials

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

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Acknowledgements

This work was funded by the National Natural Science Foundation of China (Grant No.81803303; Grant No.81874122), the Natural Science Foundation of Jiangsu Province (Grant No. BK20180674), the CAMS Initiative for Innovative Medicine (Grant No. 2017-I2M-3-004), and National Natural Science Foundation of China (Grant No. 81773539).

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Author notes

  1. Yifei Yin and Shuifang Lei are the first co-authors.

Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China

    Yifei Yin, Shuifang Lei, Qiming Yin & Rongxi Yang

  2. Department of Thyroid and Breast Surgery, The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’an, Huai’an, China

    Yifei Yin

  3. Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Lixi Li & Fei Ma

  4. Department of Breast Surgery, West China Hospital, Sichuan University, Chengdu, China

    Xiaoqin Yang

  5. Department of Clinical Laboratory, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China

    Tian Xu & Wanjian Gu

  6. Chengdu Shang Jin Nan Fu Hospital, West China Hospital, Sichuan University, Chengdu, China

    Wenjie Zhou

  7. Department of Pathology, The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’an, Huai’an, China

    Hong Li

  8. Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China

    Zhengdong Zhang

  9. Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China

    Zhengdong Zhang

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  1. Yifei Yin
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Contributions

All authors contributed to the study's conception and design. The first draft of the manuscript was written by RY, SL, and YY. RY, ZZ, and FM supervised and design the project. YY, SL, and QY performed the experiments and analyzed the results. LL, XY, TX, WZ, WG, and HL provided the materials and supervised the patient enrolment and acquisition of biological samples and clinical data. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Rongxi Yang or Zhengdong Zhang.

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Conflict of interest

Yifei Yin, Shuifang Lei, Lixi Li, Xiaoqin Yang, Qiming Yin, Tian Xu, Wenjie Zhou, Hong Li, Wanjian Gu, Fei Ma, Rongxi Yang, Zhengdong Zhang declare that they have no competing interests.

Ethics approval

Approval was obtained from the ethics committee of the Nanjing Medical University, the Chinese Academy of Medical Sciences, and West China Hospital. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

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

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The authors affirm that human research participants provided informed consent for publication of their clinic data.

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Yin, Y., Lei, S., Li, L. et al. RPTOR methylation in the peripheral blood and breast cancer in the Chinese population. Genes Genom 44, 435–443 (2022). https://doi.org/10.1007/s13258-021-01182-0

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