Young age of onset colorectal cancers

Abstract

Background

Colorectal cancer is typically a condition of older patients with only 10 % diagnosed under the age of 50 years. Often, diagnosis is delayed, but certain factors such as inherited syndromes, inflammatory bowel disease, or a family history of colorectal cancer should heighten the clinician’s awareness. This study of young colorectal cancers describes the incidence of potential contributory factors that warrant early investigations and their effect on survival outcomes.

Methods

A single-institution colorectal cancer database was queried for patients diagnosed with colorectal cancer under the age of 50. Medical records were reviewed, and patients were grouped into familial, inflammatory bowel disease-related, or sporadic cancers. Sporadic cancers without existing family history were further evaluated for genetic and molecular changes including mutations in the oncogenes KRAS and BRAF, microsatellite instability, and methylator phenotype.

Results

One hundred thirty-five patients under the age of 50 with colorectal cancer diagnosed between 1994 and 2004 were identified. Slightly under half, (44.4 %) were women. Mean age at surgery was 42.1 ± 6.7 years. Nineteen patients (14 %) had a hereditary colorectal cancer syndrome (11 hereditary non-polyposis colorectal cancer (HNPCC), 8 familial adenomatous polyposis (FAP)), and 19 (14 %) had inflammatory bowel disease (14 ulcerative colitis, 5 Crohn’s). Three patients had other cancers (brain, breast, and endometrial) and 20 % of patients had a family history of colorectal cancer outside of a defined syndrome. Overall, age-standardized 5-year survival was 66.8 % (stage I 100 %, stage II 76.5 %, stage III 63.0 %, and stage IV 0 %). Patients with genetic predisposition and inflammatory bowel disease had better 5-year survival when compared to the sporadic group (p = 0.025). Molecular profiles were available for 71 of the 77 sporadic cancers. All 71 tumors were microsatellite stable, and none had CpG island methylator phenotype. Twenty-three (32.4 %) were KRAS mutant.

Conclusion

In our cohort, a family history of colorectal cancer, known hereditary colorectal cancer syndrome, and inflammatory bowel disease account for nearly half of all cases of young colorectal cancer. Prompt investigation of symptoms is essential in patients with Sporadic early-onset colorectal cancers, which appear to arise through the classical adenoma-to-carcinoma sequence.