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.
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