Hereditary gynecologic cancer syndromes at a glance

• Hereditary gynecologic cancer syndromes are inherited, genetic predispositions that drastically increase a woman’s chance of being diagnosed with certain gynecological cancers.
• Genetic mutations cause about 5–10 percent of all cancers.
• The most common genetic mutations are the BRCA1 and BRCA2 mutations that cause breast and ovarian cancer.
• Those with the BRCA gene mutation have a 50 percent chance of passing the gene to offspring.
• Lynch syndrome is another, less common, hereditary gynecological cancer syndrome that increases a woman’s chance of getting several different types of both gynecologic and non-gynecologic cancers.

What are hereditary gynecologic cancer syndromes?

Hereditary gynecologic cancer syndromes (HGCS) are a collection of genetic causes of gynecological cancers. A syndrome is defined as regularly occurring symptoms or a condition characterized by a set of associated symptoms or indicators. Individuals with hereditary cancer syndromes inherit an established risk of getting certain cancers. If a cancer is not caused by a genetic mutation before birth, it is referred to as a sporadic cancer.

The most common and noteworthy hereditary gynecological cancer syndromes include BRCA1 and BRCA2 mutations, which cause breast and ovarian cancer. Lynch syndrome, another notable hereditary gynecological cancer syndrome, increases the risk of endometrial and ovarian cancers, as well as predisposing women to other, non-gynecologic cancers such as stomach, small intestine and colorectal cancer.

A woman’s genetic makeup and family history determine her inherent risk for contracting a gynecological cancer. If a close or immediate family member has had breast or ovarian cancer, this increases the likelihood of having a hereditary cancer syndrome. Hereditary gynecological cancers typically present at much younger ages than sporadic cancers. (Diagnosis under the age of 45 may also indicate a genetic issue causing cancer.)

Hereditary breast and ovarian cancer syndrome, BRCA1 & 2 mutations

In the general population, about 1 in 10 American women develop breast cancer, and 1.5 percent will get ovarian cancer. Women with the BRCA1 gene possess a 40 percent lifetime risk of contracting gynecological cancer and BRCA2 mutations’ risk is around 20 percent. Both women and men can possess a BRCA gene mutation, and they have a 50 percent chance of passing it along to any children.

The BRCA gene mutations are uncommon; about 1 in 500 women have one of the BRCA gene mutations. Some ethnic groups carry a higher risk of the gene mutation. For example, 1 out of every 40 Ashkenazi Jews carries the BRCA1 or BRCA2 genetic mutation.

Other family history and medical criteria may indicate a hereditary gynecological cancer syndrome:

• Breast cancer before age 45
• A close female relative, such as mother, daughter, granddaughter, sister, grandmother, aunt or niece, who has or had ovarian cancer
• Two or more close relatives on one side of the family with ovarian cancer or breast cancer before the age of 50.

Women diagnosed with ovarian cancer may consider undergoing genetic testing to confirm or dismiss a genetic mutation.

Lynch syndrome

Lynch syndrome is caused by mutated and mismatched DNA, most commonly the MSH2 and MLH1 genes. About 1 in 1,000 individuals carries this genetic mutation.

When Lynch syndrome is present, there is a markedly increased risk of endometrial cancer in women that is around 40-60 percent higher than for the general population.

Women with Lynch syndrome also have a 10 percent overall chance of getting ovarian cancer (compared with 1.5 percent for the general population). Lynch syndrome also increases a woman’s risk for ovarian and breast cancer, and for non-gynecologic cancers including pancreatic, urinary tract, small bowel and liver cancers.

Lynch syndrome may be clinically indicated by:

• Having three or more relatives with Lynch-associated cancers
• Multiple relatives with Lynch syndrome-associated cancers diagnosed before the age of 50
• A genetic test from a blood sample or tumor tissue may also confirm the presence of Lynch syndrome.

At CU Anschutz Gynecologic Oncology, experts provide advanced diagnosis and care, from surgery to radiation and chemotherapy.