| 26 27 | See page 67 for references Potential management options Management guidelines for CHEK2 mutations are currently evolving. A thorough review of family history is important to better understand cancer risks and to develop an individualized cancer screening plan. For women with CHEK2 mutations, NCCN recommends the following: · ·Annual mammogram with consideration of tomosynthesis and consideration of breast MRI beginning at age 40 or ten years before the youngest breast cancer diagnosis in the family. · ·Additional risk-reduction strategies, such as prophylactic mastectomy or the use of medication, may also be considered on an individualized basis, e.g. based on family history or mutation. For men and women: · ·Colonoscopy every 5 years, beginning at age 40 or 10 years earlier than the age at which colorectal cancer was diagnosed in a first-degree relative.(Note: Caution should be used when implementing final colonoscopy surveillance regimens in context of patient preferences and new knowledge that may emerge. ) There are currently no screening or management recommendations for other possible types of cancers associated with CHEK2. Additional screening may be individualized based on family history. EPCAM, MLH1, MSH2, MSH6, and PMS2 gene summary Lynch syndrome Gene name EPCAM, MLH1, MSH2, MSH6, PMS2 Associated syndrome Lynch syndrome Primary associated cancers Colorectal, endometrial, ovarian Frequency Approximately 1 in 450 Inheritance pattern Autosomal dominant Overview · ·Lynch syndrome accounts for approximately 3% of colorectal cancers. · ·1 in 35 colon cancers is due to a mutation associated with Lynch syndrome. · ·Mutations in MLH1 and MSH2 confer a significantly higher risk for colon cancer than mutations in MSH6 or PMS2. About Lynch syndrome Lynch syndrome, formerly called hereditary non-polyposis colorectal cancer (HNPCC), is characterized by increased risks for colon cancer and cancers of the endometrium, ovary, stomach, small intestine, hepatobiliary tract, urinary tract, brain, and skin. Five genes are associated with Lynch syndrome: MLH1, MSH2, MSH6, PMS2, EPCAM. MLH1, MSH2, MSH6, and PMS2 encode proteins involved in mismatch repair of the DNA, while deletions in EPCAM can impact MSH2 gene expression. The percentage of Lynch syndrome associated with each of the five genes is estimated as follows: · ·MLH1: 50% · ·MSH2: 40% · ·MSH6: 7%–10% · ·PMS2: