Endometrial cancer affects many women globally. While most cases arise sporadically, a notable portion can be linked to inherited genetic factors. Understanding this genetic component helps assess individual risk and guide preventative measures.
Understanding Hereditary vs. Sporadic Cancer
Cancers are broadly categorized into two types: sporadic and hereditary. Sporadic cancers develop from genetic changes that occur in cells over a person’s lifetime, often due to aging, environmental exposures, or lifestyle factors. These changes are not inherited and are confined to the tumor cells.
Hereditary cancers, in contrast, result from germline mutations, which are alterations in genes present in every cell of the body and passed down from a parent. These inherited mutations significantly increase a person’s lifetime risk of developing certain cancers. Identifying these genetic predispositions is important for personalized risk management.
Genetic Syndromes Linked to Endometrial Cancer
Lynch syndrome represents the most common genetic cause of hereditary endometrial cancer. This syndrome arises from inherited mutations in specific mismatch repair (MMR) genes, including MLH1, MSH2, MSH6, PMS2, and sometimes EPCAM. These genes are responsible for correcting errors that occur during DNA replication.
Women with Lynch syndrome have a significantly elevated lifetime risk of developing endometrial cancer, ranging from 40% to 60%, which can be comparable to or even exceed their risk for colorectal cancer. Endometrial cancer in individuals with Lynch syndrome often develops at a younger age than in the general population, typically before menopause. Mutations in MLH1 and MSH2 genes may confer a higher risk compared to MSH6 and PMS2 mutations.
Assessing Your Hereditary Risk
Assessing hereditary risk for endometrial cancer begins with evaluating personal and family medical history. Healthcare providers will inquire about cancers in close relatives, the types of cancer diagnosed, and the age at which these diagnoses occurred. A pattern of multiple cancer diagnoses across generations, particularly at younger ages, can indicate an inherited predisposition.
Genetic counseling plays a central role, providing information about hereditary cancer syndromes and guiding individuals through genetic testing implications. If a hereditary risk is suspected based on family history or tumor characteristics, genetic testing can identify specific gene mutations associated with increased endometrial cancer risk. These tests often involve analyzing DNA for mutations in the MMR genes linked to Lynch syndrome.
Strategies for Managing Hereditary Risk
For individuals with hereditary risk, such as Lynch syndrome, specialized management strategies reduce cancer risk and facilitate early detection. Increased surveillance involves regular gynecological examinations, transvaginal ultrasounds, and endometrial biopsies. These screenings typically begin at an earlier age, often between 30 and 35 years.
Risk-reducing surgeries are another important consideration, particularly for women who have completed childbearing. A prophylactic hysterectomy, the surgical removal of the uterus, with or without bilateral salpingo-oophorectomy (removal of the ovaries and fallopian tubes), can significantly lower the risk of endometrial and ovarian cancers. Lifestyle modifications, such as maintaining a healthy weight and regular physical activity, also contribute to overall risk reduction. These management plans are individualized and developed in close collaboration with healthcare providers.