Ovarian Cancer Risk Found for Normal Tissue BRCA1 Methylation

A recent study has shown that normal tissue BRCA1 methylation has an association with elevated risk for high-grade ovarian cancer development.

The study

It is already known that females who possess the BRCA1 mutations within their germline are at an elevated risk of developing high-grade ovarian cancer, but this did not formerly account for BRCA1 methylation in normal tissues. Researchers found that in certain families with high risk of breast cancer had the BRCA1 methylation in normal tissues, but not in their germline.

The authors proceeded to conduct a case-control study to find what connections there might be between the BRCA1 methylation in normal tissue and level of risk for ovarian cancer.

For the study, the researchers recruited 934 patients and 1,698 health controls, and looked into their WBCs. For analysis, they used methylation-specific quantitative polymerase chain reaction (qPCR).

Their results showed BRCA1 promoter methylation's presence within normal tissue being correlated with a heightened likelihood of developing high-grade ovarian cancer. The authors were able to find BRCA1 methylation of women of any age group, even newborn babies. As a result, they hypothesized that BRCA1 methylation may occur during the embryonic stage, and pose a threat of later development of high-grade ovarian cancer.

To confirm the results, a validation study was conducted. It was also strengthened by its consistency with the STREGA and GRIPS, which are for Strengthening the Reporting of Genetic Association Studies and Strengthening the Reporting of Genetic Risk Prediction Studies, respectively.

However, the study does suffer from one limitation. The logistics of a potential study design are immensely complex, so instead a retrospective one had been utilized. Therefore, the blood samples were collected from the patients that were a part of the study when they were initially diagnosed.

Case control

In their use of methylon-specific qPCR in the preliminary study, the researchers were able to look into the similarities and differences in the BRCA1 promoter methylation in the WBCs of the patients and healthy controls.

Similarly, the authors then produced an analysis that included 607 patients and 984 healthy controls in their efforts to validate their initial results. To do so, patients were recruited from two separate hospitals in Norway. The blood samples that were utilized had all been taken before the patients began their chemotherapy.

Their results showed that BRCA1 methylation could be found at a higher rate in those with ovarian cancer (6.4 percent) than in the healthy controls (4.2 percent). Only serous high-grade ovarian cancer patients portrayed elevated methylation (9.6 percent) as compared to patients with nonserous (5.1 percent) and low-grade serous (4 percent) ovarian cancer. The validation study was able to show confirming findings in regard to high-grade serous ovarian cancer patients (9.1 percent), healthy controls (4.3 percent), nonserous ovarian cancer (4.1 percent), and low-grade serous ovarian cancer (2.7 percent). These results were not impacted by WBC subfractions, sample storage time, or tumor burden.

WBC BRCA1 methylation was present most often in newborns (7.0 percent in comparison to 4.1 percent in young women). This leads many to believe that the risk for certain types of cancers can be determined before a baby is even born. According to findings that were published in the Annals of Internal Medicine, "normal tissue BRCA1 methylation is associated with risk for high-grade ovarian cancer and may occur as a prenatal event."

Read on to learn more about this important discovery.