Peripheral bloodBRCA1methylation profiling to predict familial ovarian cancer

Abstract

Objective: Familial cancer appears at a young age and its incidence is increasing. About 12% of familial ovarian cancer cases are associated with BRCA1/2 mutations (BRCAm). In this study, we investigated BRCA1 methylation may predict ovarian cancer in those with a family history of cancer (FHC) but without BRCA1/2 mutations (BRCAwt). Methods: Using peripheral blood DNA from 55 subjects without a history of cancer [cancer(−)] and 52 ovarian cancer patients, we examined BRCA1 promoter methylation through bisulfite sequencing of the promoter and expressed the results as the cumulative methylation index. Then, we evaluated the BRCA1 promoter methylation according to BRCA1/2 germline mutations. Results: BRCA1 methylation was more prevalent in the BRCAm cancer(−) group than in the BRCAwt cancer(−) group and ovarian cancer patients (p=0.031 and p=0.019, respectively). In the BRCAwt cancer(−) group, BRCA1 methylation was more prevalent in those with an FHC than in those without one and in the BRCAm cancer(−) group with an FHC (p=0.001 and p<0.001, respectively). Conclusion: Our data suggest a predictive role of BRCA1 methylation profile for ovarian cancer in those without a history of cancer but with an FHC. BRCA1 methylation has important implications for diagnostic and predictive testing of those with BRCAwt cancer(−) status with FHC.

MicroRNA‑126 expression in the peripheral white blood cells of patients with breast and ovarian cancer is a potential biomarker for the early prediction of cancer risk in the carriers of methylated BRCA1

“…There is a well-established association between BRCA1 promoter methylation in peripheral blood cells and the risk of BC and OC (20,22,23,36). However, less is known about its role in the cancer risk of CF BRCA1-methylated females.…”

“…In 2008, Snell et al (15) made a breakthrough, finding that methylated BRCA1 promoter is observed in peripheral white blood cells (WBC) of patients with mutation-negative familial BC and cancer-free controls. Since then, several studies have shown the association of WBC BRCA1 promoter methylation with the risk of developing early onset BC and high-grade serous OC, with pathological features similar to those of patients with germline mutated BRCA1 (15)(16)(17)(18)(19)(20)(21)(22)(23)(24). The detection of BRCA1 promoter methylation in the WBCs of cancer-free (CF) females has raised the question of whether those individuals are at risk of developing breast and ovarian cancer (15,16,20,21,24,25).…”

MicroRNA-155-5p, Reduced by Curcumin-Re-Expressed Hypermethylated BRCA1, Is a Molecular Biomarker for Cancer Risk in BRCA1-methylation Carriers

“…Both BRCA1-mutated and BRCA1-methylated neoplasms have similar pathological features [5,7]. Although mounting evidence suggests a link between constitutional BRCA1 promoter methylation and the risk of BC and OC development [8][9][10][11][12][13][14][15][16][17], more research is needed to determine whether cancer-free BRCA1-methylation carriers are at an increased risk of cancer development in the same way that germline BRCA1 mutation carriers are.…”

Current data and future perspectives on DNA methylation in ovarian cancer (Review)

“…In the study by Jung et al ( 28 ) comparing the peripheral blood DNA of 55 subjects with no history of cancer and 52 patients with OC, higher rates of BRCA1 methylation were observed in individuals with a family history of cancer, and the presence of BRCA1 methylation increased the risk of developing familial and sporadic EOC. Therefore, BRCA1 methylation testing is an invaluable diagnostic and prognostic tool for individuals who are aware of their BRCA mutation status and have a strong family history.…”