Colorectal cancer is extremely rare in childhood.
Published case series reporting children and adolescents with colorectal cancer have not focused on the underlying genetic aspects of the tumor or genetic susceptibility of the families.
Dr Durno and colleagues from Ontario examined a cohort of patients with early onset colorectal cancer.
The researchers determined whether a specific genetic predisposition could be elucidated.
|Microsatellite instability was found in tumors from 8 of 11 patients|
In particular, the researchers focused on whether DNA mismatch repair gene deficiency which causes hereditary non-polyposis colorectal cancer could be elucidated.
Patients with colorectal cancer 24 years of age were identified from a database at the Familial Gastrointestinal Cancer Registry at Mount Sinai Hospital, Toronto.
The researchers ascertained detailed pedigrees from the proband or parents.
The research team tested tumors for microsatellite instability, a hallmark of hereditary non-polyposis colorectal cancer.
Germline mismatch repair gene mutations MSH2 and MLH1 were sought in some cases and clinical data were obtained by chart audit.
The researchers found that among 1382 probands in the registry, 16 colorectal cancer patients were 24 years or younger at the time of diagnosis.
The team identified microsatellite instability in tumors from 8 of 11 evaluated patients.
Germline mutations in mismatch repair genes were identified in 6 of 12 patients, including 3 with MSH2, 2 with MLH1, and 1 with PMS2.
The researchers reported that 10 of 16 families met the Amsterdam criteria for hereditary non-polyposis colorectal cancer.
Among these, 6 were screened for mismatch repair gene mutations and 3 were found to carry MSH2 or MLH1 germline mutations.
The researchers observed that colorectal cancers were located in the rectum/sigmoid in 9, in the splenic flexure in 2, in hepatic flexure in 3, and in the caecum of 2.
The team noted that 7 out 16 of these young cases developed additional malignancies, including gastrointestinal in 8 and extraintestinal in 4 during follow up.
Dr Durno and team concluded, “Patients with early onset colorectal carcinoma often have an inherited predisposition to the disease.”
“Tumors with high frequency microsatellite instability and germline mutations of mismatch repair genes are sufficiently common in this patient population that they should be considered.”
“However, family histories may not satisfy the stringent Amsterdam criteria for hereditary non-polyposis colorectal cancer.
“Young colorectal cancer patients are at increased risk of developing second gastrointestinal and extraintestinal malignancies. “