Breast cancer
Prostate cancer
Li-Fraumeni /Li-Fraumeni-like Syndrome

CHEK2 encodes a Serine/threonine-protein kinase which plays a critical role in DNA damage signaling pathways¹. CHEK2 directly phosphorylates and regulates the functions of p53 and BRCA1 ^2,3. Most women with breast and/or ovarian cancer are not carriers of mutant BRCA1 or BRCA2. Multiple studies have shown that a CHEK2*1100delC confers about a two-fold increased risk of breast cancer in unselected females and a 10-fold increase in males ^4,5. Moreover, studies have shown that first-degree relatives of bilateral breast cancer cases who carried the CHEK2*1100delC allele had an eight-fold increased risk of breast cancer ⁶. The cumulative risk by age 80 years was 58·8% (95% CI 33·8–85·3) for CHEK2*1100delC carriers with a bilaterally affected firstdegree relative ⁶ . The CHEK2 mutations were identified in women with breast cancer and/or ovarian cancers ^4,13. A CHEK2 mutation was also reported in 18.2% families with hereditary breast and colorectal cancer (HBCC)¹⁵ and was associated with a two-fold increased risk of colon cancer ^16,17. It has been suggested that CHEK2 functions as a low-penetrance susceptibility gene for cancers and multiplies the risks associated with other gene(s) to increase cancer risk ^{4, 5, 6, 15}. Heterozygous germline mutations in CHEK2 have been identified in about 4% patients with prostate cancer ^{7, 8, 9}. Germline mutations have also been detected in at least one family with classic Li-Fraumeni syndrome (LFS) ^{10, 11} and in other families with Li-Fraumeni-like syndrome¹² or with a subtype of LFS known as “phenotypically suggestive of LFS”^{10, 11, 12}.