Basic Sciences Research, Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH&RC), 7-A, Block R-3, Johar Town, Lahore, 54770, Pakistan.
Department of Cancer Registry and Clinical Data Management, SKMCH&RC, Lahore, Pakistan.
Breast Cancer Res Treat. 2023 Nov;202(2):377-387. doi: 10.1007/s10549-023-07068-x. Epub 2023 Aug 1.
Constitutional BRCA1 promoter methylation has been identified as a potential risk factor for breast cancer (BC) in the Caucasian population. However, this data is lacking for BC patients of Asian origin. Therefore, we assessed the contribution of constitutional BRCA1 promoter methylation in Pakistani BC patients.
A total of 385 BRCA1/2-negative index BC patients (197 early-onset BC (≤ 30 years), 152 familial BC, 17 familial BC and ovarian cancer, 19 male BC) and 107 healthy controls were screened for the constitutional BRCA1 promoter methylation by methylation-sensitive high-resolution melting assay. Overall, 131 patients displayed triple-negative BC (TNBC) and 254 non-TNBC phenotypes. The prevalence of BRCA1 promoter methylation was calculated based on clinicopathological characteristics using univariable and multivariable logistic regression models.
Constitutional BRCA1 promoter methylation was identified in 19.5% (75/385) of BC patients and 13.1% (14/107) of controls. The frequency of methylation was higher in early-onset BC (23.4% vs. 13.1%, P = 0.035) and TNBC patients (29.0% vs. 13.1%, P = 0.004) compared to controls. Methylation was also more prevalent in patients with high-grade than low-grade tumors (21.7% vs. 12.2%, P = 0.034) and progesterone receptor (PR)-negative than PR-positive tumors (26.0% vs. 13.9%, P = 0.004). Constitutional BRCA1 promoter methylation remained independently associated with TNBC phenotype (odds ratio 1.99; 95% CI 1.12-3.54; P = 0.02) after adjusting for BC diagnosis age, tumor grade, ER, and PR status.
Constitutional BRCA1 promoter methylation is associated with TNBC and can serve as a non-invasive blood-based biomarker for Pakistani TNBC patients.
BRCA1 启动子甲基化已被确定为高加索人群乳腺癌（BC）的潜在风险因素。然而，亚洲裔 BC 患者的数据尚缺乏。因此，我们评估了巴基斯坦 BC 患者中 BRCA1 启动子甲基化的作用。
共筛选了 385 例 BRCA1/2 阴性指数 BC 患者（197 例早发性 BC（≤30 岁）、152 例家族性 BC、17 例家族性 BC 和卵巢癌、19 例男性 BC）和 107 例健康对照者，采用甲基化敏感高分辨率熔解曲线法检测 BRCA1 启动子甲基化。总体而言，131 例患者表现为三阴性 BC（TNBC），254 例为非 TNBC 表型。基于临床病理特征，采用单变量和多变量逻辑回归模型计算 BRCA1 启动子甲基化的患病率。
在 385 例 BC 患者中有 19.5%（75/385）和 107 例对照者中有 13.1%（14/107）存在 BRCA1 启动子甲基化。与对照组相比，早发性 BC（23.4% vs. 13.1%，P=0.035）和 TNBC 患者（29.0% vs. 13.1%，P=0.004）中甲基化的频率更高。在高级别肿瘤患者中，甲基化的发生率也高于低级别肿瘤患者（21.7% vs. 12.2%，P=0.034），孕激素受体（PR）阴性肿瘤患者高于 PR 阳性肿瘤患者（26.0% vs. 13.9%，P=0.004）。在调整 BC 诊断年龄、肿瘤分级、ER 和 PR 状态后，BRCA1 启动子甲基化与 TNBC 表型仍独立相关（优势比 1.99；95%CI 1.12-3.54；P=0.02）。
BRCA1 启动子甲基化与 TNBC 相关，可作为巴基斯坦 TNBC 患者非侵入性的基于血液的生物标志物。
