Germline TP53 Mutations in Patients With Early-Onset Colorectal Cancer (Li-Fraumeni syndrome-ovarian cancer...)

JAMA - open access

....Li-Fraumeni syndrome is an inherited cancer syndrome, usually caused by germline TP53 mutations, in which patients classically develop early-onset cancers, including leukemias, brain tumors, sarcomas, breast carcinomas, and adrenocortical carcinomas.^7- 10 Beyond these so-called core cancers, data have shown that TP53 mutation carriers are also at increased risk for a wide array of other malignant neoplasms, including bronchoalveolar, pancreatic, gastric, ovarian, and colorectal cancers.<sup>6,10- ....

eg. ....</sup> This proband’s family history included a sister with ovarian cancer at age 39 years, a mother with breast and ovarian cancers at ages 60 and 65 years, respectively, and a daughter with glioblastoma at age 41 years, none of whom had had testing for the TP53 or BRCA2 mutations.^30.....

At a Glance

• Individuals with Li-Fraumeni syndrome (LFS) caused by germline TP53 mutations are estimated to have a 73% to 100% lifetime risk of cancer, including colorectal cancer (CRC).
• The purpose of this study was to determine the frequency of germline TP53 alterations in individuals with early-onset CRC.
• Of 457 participants diagnosed as having CRC at age 40 years or younger, 1.3% carried germline TP53 alterations.
• None of the TP53 probands in this study had a personal or family cancer history that fulfilled clinical LFS criteria.
• Cancer risk in TP53 mutation carriers may be different in patients presenting with early-onset CRC compared with those who present with classic LFS family histories.