The incidence of colorectal cancer in young patients is rising. Genetic predisposition is postulated to be responsible for up to 30% of all colorectal cancer. However, only 10% are detected currently. We postulate that the current approach with a detailed family history may be insufficient. More detailed genetic screening has to done for this group of patients.
We collected clinical data and blood samples from patients referred to a tertiary cancer centre from November 2014 to December 2016. All patients were less than 50 years old. Targeted genome sequencing was used to identify germline mutations in an array of cancer associated genes. These genes were screened for pathogenicity using the classification guidelines of the American College of Medical Genetics and Genomics.
91 young patients were diagnosed with colorectal cancer. 5 patients (5.5%) had Lynch syndrome by Amsterdam II criteria. 2 patients (2.2%) had tumours with microsatellite instability. Using targeted genomic sequencing, we identified 9 patients (9.9%) with pathogenic or likely pathogenic variants. These were 4 mutations in APC, 1 mutation in ATM, 2 mutations in MUTYH and 2 mutations in RET. No pathogenic germline mutations were found in the mismatch repair genes MLH1, MSH2, MSH6, PMS2, EPCAM.
1 in 10 young patients with colorectal cancer was found to have germline pathogenic variants. Notably, none of the patients in this Asian cohort has a germline mutation in the mismatch repair genes. With a detailed history, we only managed to identify 1 in 20 patients. It is important to screen for germline mutations in young patients with colorectal cancer as these patients have a high risk for development of metachronous colorectal cancer. They will benefit from close surveillance and genetic counselling.
Clinical trial identification
Legal entity responsible for the study
National Cancer Centre Singapore.
Has not received any funding.
All authors have declared no conflicts of interest.