| 24 25 | See page 67 for references CHEK2 gene summary CHEK2-associated hereditary cancer Gene name CHEK2 Associated syndrome CHEK2-associated hereditary cancer Primary associated cancers Breast, colorectal Frequency Varies by ethnicity Inheritance pattern Autosomal dominant Overview · ·CHEK2 is a gene associated with a moderate risk for breast and colon cancer. · ·Because CHEK2 mutations do not always explain all of the cancer risk in a family, family members who test negative for a known familial CHEK2 mutation may still be at increased risk for cancer based on the family history. · ·Cancer risks associated with mutations in CHEK2 are strongly influenced by family history, as well as the specific mutation identified. About CHEK2 First described in 1999, the CHEK2 gene provides instructions for making a protein called checkpoint kinase 2. This protein acts as a tumor suppressor and is activated in response to DNA damage. CHEK2 has since been associated with moderate penetrance and a relative risk of breast cancer of 2 to 4, as well as a moderately increased risk for colon cancer. However, absolute risks for individuals who are identified to have a CHEK2 mutation are strongly influenced by family history and the specific mutation(s) identified. A thorough family history review is important to better understand cancer risks and to develop an individualized cancer screening plan. Cancer risks Female breast cancer: In general, women identified to have a mutation in CHEK2 have an estimated lifetime breast cancer risk of 20%–25%, compared to the general population risk of 12%. This risk may be higher in some individuals who have a family history of breast cancer as outlined in the table below: Family history of breast cancer Estimated lifetime female breast cancer risk No family history 20%–25% One first-degree relative 34% One second-degree relative 28% One first- and one second-degree relative 44% Data adapted from Cybulski et al (2011). Study limited to patients of European descent and may not be reflective of risk in other ethnicities Risk for a second primary breast cancer is reported to be increased in CHEK2 mutation carriers with breast cancer. This risk is estimated to be 29% within 10 years from first diagnosis. Other cancers: · ·Meta-analyses investigating the risk of colon cancer associated with the CHEK2 mutations I157T and 1100delC suggest an OR of 1.6 and 2.8, respectively. This risk is influenced by family history. The colon cancer risk associated with other mutations has not been well studied. · ·Mutations in CHEK2 have been reported with many other types of cancers, such as prostate cancer. However, more research is needed to determine the exact cancer types and possible associated risks.