AS543 - Exploring WBC BRCA1 methylation as a risk factor for incidental cases of high grade serous ovarian cancer and triple-negative breast cancer in WHI

Investigator Names and Contact Information

Per Lonning (per.lonning@helse-bergen.no)

Introduction/Intent

BRCA1 germline mutations are associated with a high risk of both ovarian and breast cancer. Among breast cancers, 80% of tumors arising in BRCA1 mutation carriers belong to the triple-negative subtype. Recently, we explored normal white blood cell (WBC) BRCA1 promoter methylation in two independent Norwegian hospital-based patient cohorts versus two independent population-based control groups1. We found BRCA1 promoter methylation on average among 4.3% of adult females without cancer, among 6.4% of patients diagnosed with an ovarian cancer (OC; all subtypes), but among 9.3% within the subgroup of OC patients diagnosed with a high-grade serous ovarian cancer (HGSOC). Thus, in our exploratory dataset, WBC BRCA1 methylation was associated with an OR for ovarian cancer (OC) of 1.83 (95% CI 1.27 – 2.63) and in the verification set 1.44 (CI 0.97-2.15). As for HGSOC, the OR was 2.91 (1.85 – 4.56) and 2.22 (1.40 – 3.52), respectively. BRCA1 methylation did not affect the risk for other types of OC.

In addition, we have unpublished data for incidental breast cancer from the Norwegian CONOR cohort. Here, we found a non-significant OR of 1.24 (CI 0.89-1.71) for the total cohort. However, the data set did not contain information regarding hormone receptor and HER2 status in order to estimate OR within the subgroup of patients with triple-negative breast cancer (TNBC).

Our aims for the current WHI study are the following:

  1. Explore the OR for incidental TNBC related to WBC BRCA1 promoter methylation status across the combined WHI cohorts based on pre-defined thresholds.
  2. Explore the OR for incidental HGSOC related to WBC BRCA1 promoter methylation status across the combined WHI cohorts.
  3. Exploratory analyses: examine the OR for TNBC as well as HGSOC related to methylation of particular CpGs across the promoter area.
THE WOMEN’S HEALTH INITIATIVE
THE WOMEN’S HEALTH INITIATIVE

The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services.

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