Hereditary ovarian cancer

How common is ovarian cancer?

Ovarian cancer is the seventh most common cancer in Swedish women and accounts 3% of all cancers in women¹. The average lifetime risk of developing ovarian cancer is between 1–2%^1,2. Ovarian cancer is difficult to detect at an early stage, which likely contributes to its high mortality rate – namely the highest of all gynecological cancers. While ovarian cancer affects women of all ages, it is rare to be diagnosed before thirty years of age.

What causes ovarian cancer?

About 80 to 85% of all ovarian cancer¹ is caused by DNA damage, which can occur during DNA replication or be due to environmental factors. DNA damage occurs all the time and most of the time it is repaired. But with age comes an accumulation of DNA damage, and in turn a higher likelihood that a normal cell transforms into a cancer cell. Age is therefore the leading risk factor for cancer.

The remaining 15 to 20% of all ovarian cancer is explained by hereditary factors¹. The impact of hereditary factors on the risk of developing breast cancer can range from small to very large. What they have in common is that individuals with a hereditary risk of cancer are born with one high-risk genetic variant or several low-risk DNA variants that are present in all cells. These variants often affect proteins involved in DNA repair or in other ways protect cells from becoming cancer cells. Therefore, the ability to protect cells from becoming cancer cells may be impaired which results in DNA damage. Normal cells in individuals with a hereditary risk of cancer thus have a higher probability of becoming cancer cells.

Hereditary factors in ovarian cancer contribute most to an increased risk of epithelial ovarian cancer, which constitutes 90% of all ovarian cancer.

Underlying genetic factors

One or more ovarian cancer diagnoses in a family is enough to suspect hereditary factors are at play. According to national guidlines¹, all women that are diagnosed with ovarian cancer should be offered genetic testing.

In a subset of women with hereditary ovarian cancer it is possible to identify a causative pathogenic varian (mutation). Between 65–85% of the variants are found in the BRCA1 and BRCA2 genes, which are associated with a moderate to high risk of ovarian cancer¹. All women with ovarian cancer should therefore be offered genetic screening of these two genes according to national guidelines.

Between 10-15% of the variants are found in other genes associated with a low or moderate risk of ovarian cancer. Among these genes are MLH1, MSH2, MSH6, PMS2 and EPCAM (these genes are also associated with Lynch syndrome) as well as BRIP1, RAD51C and RAD51D. Women with ovarian cancer may be offered genetic testing of these additional genes according to national guidelines¹. Furthermore, pathogenic variants in STK11 and PALB2 are associated with a low or moderate risk of ovarian cancer³. All above-described genes are included in the GeneMate^® test for hereditary cancer*.

Risk-reducing measures for healthy carriers

Healthy females with a pathogenic variant in genes contributing to an increased risk of ovarian cancer can reduce their risk by removing their ovaries and fallopian tubes through prophylactic surgery. For carriers of a pathogenic variant in BRCA1, MLH1, MSH2, MSH6, PMS2 or EPCAM prophylactic surgery is recommended between 35–40 years of age. Carriers of a pathogenic variant in BRCA2 are recommended prophylactic surgery between 40–50 years of age. Carriers of a pathogenic variant in BRIP1, RAD51C or RAD51D are recommended prophylactic surgery at 50–55 years of age.

Pathogenic variants in BRCA1 and BRCA2 are also associated with an increased risk of breast cancer. Female carriers are therefore recommended additional breast cancer screening. Pathogenic variants in MLH1, MSH2, MSH6, PMS2 and EPCAM are also associated with an increased risk of other cancers, the most common being colorectal cancer and uterine cancer. Carriers of variants in these genes are therefore recommended additional colonoscopy screening.

Risk-reducing measures in the absence of a known variant

As previously mentioned, it is only possible to identify underlying genetic factors in a subset of those with hereditary ovarian cancer. As a result, there are families with an increased risk for ovarian cancer as determined by their family history, but without an identifiable variant. Women with one first-degree relative with ovarian cancer have about a 3% risk of developing ovarian cancer. The risk increases as the number of affected family members increases.

In this case, cancer screening recommendations will depend on the family’s cancer history. The GeneMate^® test combines a genetic test with an assessment of your family’s cancer history, either of which can indicate an increased risk of ovarian cancer. Therefore, it is important that you provide comprehensive information about your family’s cancer history (if available). We will help you get in contact with the appropriate care giver if cancer screening is motivated.

GeneMate^®tests for pathogenic variants in the following genes: BRCA1, BRCA2, PALB2, STK11, MLH1, MSH2, MSH6, PMS2 och EPCAM. The complete panel is available at genemate.se.

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