启动子甲基化是癌症生物标记物的激活机制之一。根据多个人群的研究，乳腺癌肿瘤中的RARB和GSTP1等抑癌基因与正常组织相比已被报道为高度甲基化的。本病例对照研究旨在使用液体活检方法确定RARB和GSTP1基因启动子甲基化比值（PMR）与秘鲁患者乳腺癌及其临床病理学变量的关联。共有58名乳腺癌患者和58名与之年龄相匹配的健康对照组参与了本研究。我们从血浆中提取了细胞外DNA（cfDNA），并通过亚硫酸盐转化该DNA。进行甲基亮灯聚合酶链式反应以获取研究基因的PMR值。我们确定了PMR与乳腺癌以及其他临床病理学变量之间的关联。并得出了这些基因的PMR的敏感性和特异性。 乳腺癌与RARB PMR（OR = 1.90，95% CI [0.62-6.18]，p = 0.210）或GSTP1 PMR（OR = 6.57，95% CI [0.75-307.66]，p = 0.114）之间没有显著的关联。RARB + GSTP1 PMR的组合与乳腺癌（OR = 2.81，95% CI [1.02-8.22]，p = 0.026），50岁以下的对照组（p = 0.048），50岁以上的患者（p = 0.007）以及绝经后的患者（p = 0.034）有关。这两个基因的PMR显示了86.21%的特异性和31.03%的敏感性。RARB + GSTP1基因的启动子甲基化与秘鲁乳腺癌、年龄较大及绝经后的患者有关。启动子甲基化的RARB + GSTP1基因需进一步验证，以用作液体活检的生物标志物，并作为对50岁以下无症状妇女进行进一步检测的建议依据。 © 2023 Wiley Periodicals LLC发表的《分子遗传学与基因组医学》是作者的署名。

Promoter hypermethylation is one of the enabling mechanisms of hallmarks of cancer. Tumor suppressor genes like RARB and GSTP1 have been reported as hypermethylated in breast cancer tumors compared with normal tissues in several populations. This case-control study aimed to determine the association between the promoter methylation ratio (PMR) of RARB and GSTP1 genes (separately and as a group) with breast cancer and its clinical-pathological variables in Peruvian patients, using a liquid biopsy approach.A total of 58 breast cancer patients and 58 healthy controls, matched by age, participated in the study. We exacted cell-free DNA (cfDNA) from blood plasma and converted it by bisulfite salts. Methylight PCR was performed to obtain the PMR value of the studied genes. We determined the association between PMR and breast cancer, in addition to other clinicopathological variables. The sensitivity and specificity of the PMR of these genes were obtained.A significant association was not found between breast cancer and the RARB PMR (OR = 1.90; 95% CI [0.62-6.18]; p = 0.210) or the GSTP1 PMR (OR = 6.57; 95% CI [0.75-307.66]; p = 0.114). The combination of the RARB + GSTP1 PMR was associated with breast cancer (OR = 2.81; 95% CI [1.02-8.22]; p = 0.026), controls under 50 years old (p = 0.048), patients older than 50 (p = 0.007), and postmenopausal (p = 0.034). The PMR of both genes showed a specificity of 86.21% and a sensitivity of 31.03%.Promoter hypermethylation of RARB + GSTP1 genes is associated with breast cancer, older age, and postmenopausal Peruvian patients. The methylated promoter of the RARB + GSTP1 genes needs further validation to be used as a biomarker for liquid biopsy and as a recommendation criterion for additional tests in asymptomatic women younger than 50 years.© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.