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The association between RAPSN methylation in peripheral blood and breast cancer in the Chinese population


DNA methylation in peripheral blood is associated with breast cancer (BC) but has mainly been studied in Caucasian populations. We investigated the association between blood-based methylation of receptor-associated protein of the synapse (RAPSN) and BC in Chinese population. The methylation levels of 12 RAPSN CpG sites were quantitatively evaluated by mass spectrometry in two case–control studies with 283 sporadic BC cases and 331 controls totally. The association was analyzed by logistic regression adjusted for covariants. The RAPSN methylation levels in patients with variant clinical characteristics were investigated by non-parametric tests. We found a significant association between BC and altered RAPSN methylation in blood in women at premenopausal and perimenopausal (age < 50 years old), but not in the elder women. This was approved by two independent case–control studies as well as by combining the subjects of the two studies (taken all subjects together, age < 50 years old, per 5% of methylation, odds ratio (OR) range from 1.17 to 1.30 for two CpG sites; OR = 0.75 for one CpG site; all p values < 0.02). This age-related RAPSN methylation was further modified by human epidermal growth factor receptor 2 (HER2) status (age < 50 years old, HER2 negative, per 5% of methylation, OR range from 1.27 to 1.48 for two CpG sites; OR = 0.76 for one CpG site; all p values < 0.02). We elucidated an association between BC and blood-based RAPSN methylation influenced by age and the status of HER2 in Chinese population.

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This work was funded by the National Natural Science Foundation of China (Grant Nos. 81803303 and 81874122), the Natural Science Foundation of Jiangsu Province (Grant No. BK20180674), the CAMS Initiative for Innovative Medicine (Grant No. 2017-I2M-3-004), the Key Program of Science and Technology Department of Sichuan Province (Grant No. 2019YFS0377), and the Jiangsu Funding (WSW-009).

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The first draft of the manuscript was written by RY and SL. RY and FM supervised and design the project. SL and QY performed the experiments and analyzed the results. LL, XY, TX, WZ, WG, and FM provided the materials and supervised the patient enrollment and acquisition of biological samples and clinical data. All authors read and approved the final manuscript.

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Correspondence to Fei Ma or Rongxi Yang.

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All procedures were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The studies involving human participants were reviewed and approved by the Ethics Committee of Nanjing Medical University, the Ethics Committee of Chinese Academy of Medical Sciences, and the Ethics Committee of West China Hospital.

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Lei, S., Li, L., Yang, X. et al. The association between RAPSN methylation in peripheral blood and breast cancer in the Chinese population. J Hum Genet 66, 1069–1078 (2021).

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