Is Ovarian Cancer Hereditary? What Are the Genetic Risk Factors?

Approximately %10-15 of ovarian cancers are hereditary. Hereditary cancersoccur when mutations in particular genes are inherited, causing certain cancer types in offspring.

What Are the Most Common Mutations in Hereditary Ovarian Cancer?

The commonest mutations in hereditary ovarian cancer occur in BRCA1 and BRCA2. BRCA (BReast CAncer) genes repair DNA damage; when mutated, damage accumulates and causes cancerous transformation. Among people diagnosed with ovarian cancer, 15 percent have a mutation in one BRCA gene.

Importantly, not everyone with an inherited BRCA mutation develops cancer. BRCA mutations also occur without family history or an inherited cancer syndrome; these are sporadic mutations.

Other genes associated with hereditary ovarian cancer include tumor suppressors TP53, PTEN, CDH1, ATM, CHEK2 and PALB2.

• Also, people with Lynch syndrome have a 12 percent increase in ovarian cancer risk.
• Rare mutations in RAD51C and RAD51D increase ovarian cancer risk by 10 percent.
• STK11 mutations increase ovarian cancer risk by 18 percent.

What Are the Cancer Risks Associated with Hereditary Ovarian / Breast Cancer?

Cancer risks in women carrying inherited mutations associated with breast or ovarian cancer:

• Lifetime breast cancer risk between %50 and %80
• Breast cancer risk after age 50 between %30 and %50

Lifetime ovarian cancer risk:

• For women with BRCA1 mutations, between %25 and %50
• For women with BRCA2 mutations, between % 15 and %30

Risk of a second breast cancer between % 40 and % 60

Risks have also been calculated for men

Lifetime breast cancer risk:

• For men with BRCA1 mutations, between %1 and %2
• For men with BRCA2 mutations, %6

Lifetime prostate cancer risk:

• For men with BRCA 2 mutations, %2

When Should Genetic Testing Be Performed for Hereditary Ovarian Cancer?

Criteria have been defined for genetic counseling and genetic testing in hereditary ovarian cancer. Not every patient undergoes testing. The American National Clinical Cancer Guideline lists genetic counseling criteria for patients diagnosed with ovarian cancer as follows:

• A known cancer-associated mutation in the patient's family or community
• Breast cancer diagnosis before age 50
• A diagnosis of triple-negative breast cancer
• Two or more primary breast tumors
• A relative diagnosed with breast cancer before 50
• A relative diagnosed with ovarian cancer
• Breast or pancreatic cancer in two or more relatives
• A relative with breast cancer alongside pancreatic, prostate, sarcoma, adrenocortical, endometrial, blood, thyroid or breast cancer

Criteria also exist for healthy individuals without cancer but with a family history:

• A known cancer-associated mutation in the family
• Two or more primary breast tumors in a family member
• Breast cancer in 2 or more relatives on the maternal or paternal side
• Ovarian cancer in the family
• Breast cancer before 45 in first- or second-degree relatives
• A relative with breast cancer alongside pancreatic, prostate, soft tissue sarcoma, adrenocortical, brain, endometrial, blood, thyroid or stomach cancer

Genetic counseling is recommended if at least one criterion is met.

To identify hereditary ovarian cancer, genetic tests have been developed, analyzing genes selected according to scientific evidence. These tests use blood samples. A medical oncologist and cancer genetics specialist interpret and evaluate results. In our country, some university hospitals, private hospitals and private genetic testing companies provide these tests.