Germline Mutations Studied In Patients With Family History Of Early Onset Colon Cancer

Matthew B. Yurgelun, MD Instructor in Medicine Harvard Medical SchoolMedicalResearch.com Interview with:
Matthew B. Yurgelun, MD
Instructor in Medicine
Harvard Medical School

Medical Research: What is the background for this study? What are the main findings?

Dr. Yurgelun: Germline mutations in the TP53 gene are linked to Li-Fraumeni syndrome, which is an inherited syndrome associated with a 73-100% lifetime risk of cancer. Classically, cancers linked to Li-Fraumeni syndrome include early-onset breast cancer, leukemias, soft tissue sarcomas, brain cancer, and adrenocortical cancer, although recent data have shown an increased risk of colorectal cancer as well.  Our study’s primary aim was to determine the frequency of germline TP53 mutations in patients with early-onset colorectal cancer.

We studied 457 patients from the multinational Colon Cancer Family Registry who were diagnosed with colorectal cancer at age 40 or younger, and found that 1.3% carried a germline alteration in the TP53 gene.  None of these individuals had personal or family histories of cancer that fulfilled clinical criteria for Li-Fraumeni syndrome.

Medical Research: What should clinicians and patients take away from your report?

Dr. Yurgelun: Comprehensive strategies for germline evaluation – such as multigene panel testing and whole exome sequencing – are becoming more commonly available for patients with cancer.  With the increasing use of such strategies for germline assessment, our data suggest that TP53 mutations will be found in patients with early-onset colorectal cancer who otherwise lack classic histories for Li-Fraumeni syndrome, yet the clinical significance of this remains unclear. For patients found to carry TP53 mutations in the setting of early-onset colorectal cancer but no other clinical features of LFS, our data suggest that such probands may not have the 73-100%  lifetime risk of classic LFS cancers typically quoted for TP53 mutation carriers, although confirmatory studies are certainly needed.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Yurgelun: Further data is needed to determine which patients with early-onset colorectal cancer should be considered for germline TP53 mutation analysis. Our data suggest that further research is needed to clarify the clinical significance and optimal management strategies for patients with germline TP53 mutations who otherwise lack clinical histories suggestive of Li-Fraumeni syndrome.

Citation:

MedicalResearch.com Interview with: Matthew B. Yurgelun, MD (2015). Germline Mutations Studied In Patients With Family History Of Early Onset Colon Cancer