Lei Shuifang, Li Lixi, Yang Xiaoqin, Yin Qiming, Xu Tian, Zhou Wenjie, Gu Wanjian, Ma Fei, Yang Rongxi
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China.
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.
J Hum Genet. 2021 Nov;66(11):1069-1078. doi: 10.1038/s10038-021-00933-x. Epub 2021 May 6.
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.
外周血中的DNA甲基化与乳腺癌（BC）相关，但主要是在白种人群体中进行研究。我们调查了中国人群中基于血液的突触受体相关蛋白（RAPSN）甲基化与BC之间的关联。在两项病例对照研究中，共纳入283例散发性BC病例和331例对照，通过质谱法定量评估了12个RAPSN CpG位点的甲基化水平。通过对协变量进行调整的逻辑回归分析该关联。通过非参数检验研究了具有不同临床特征患者的RAPSN甲基化水平。我们发现，绝经前和围绝经期（年龄<50岁）女性的BC与血液中RAPSN甲基化改变之间存在显著关联，而老年女性则无此关联。这一结果在两项独立的病例对照研究以及两项研究对象合并分析中均得到证实（将所有研究对象合并，年龄<50岁，每5%甲基化水平，两个CpG位点的比值比（OR）范围为1.17至1.30；一个CpG位点的OR = 0.75；所有p值<0.02）。这种与年龄相关的RAPSN甲基化还受到人表皮生长因子受体2（HER2）状态的进一步影响（年龄<50岁，HER2阴性，每5%甲基化水平，两个CpG位点的OR范围为1.27至1.48；一个CpG位点的OR = 0.76；所有p值<0.02）。我们阐明了中国人群中BC与受年龄和HER2状态影响的基于血液的RAPSN甲基化之间的关联。
