The methylator pathway of colorectal carcinogenesis, characterized by CpG island hypermethylation and BRAF mutations, accounts for ≈25% of colorectal cancers. Because these cancers tend to be right sided and because DNA methylation in the right colon increases with age, we expect an increasing proportion of right-sided cancer over time. Conversely, we expect young patients (age <50 y) to have less methylated and fewer right-sided cancers
The purpose of this study was to analyze the distribution and genetic traits of colorectal cancer from different age groups.
This was a retrospective cohort study.
The study was conducted at a high-volume tertiary referral center.
Patient samples included those from our colorectal cancer biobank of resected colorectal cancer specimens.
Tumor CpG island hypermethylation, microsatellite instability, and mutations in KRAS and BRAF oncogenes were analyzed in resected specimens and stratified by age and tumor location. Comparisons included age >50 or <50 years and decade of diagnosis (≤50, 51–60, 61–70, 71–80, and >81 y). Patients with IBD or hereditary syndromes were excluded.
A total of 497 colorectal cancers were analyzed (266 men and 231 women); 57 patients (11.5%) were ≤50 years of age. No young cancers (0/57) were hypermethylated compared with 97 (22%) of 440 cancers of patients aged >50 years (p < 0.001). An increasing percentage of tumors were CpG island phenotype high with each decade of age at diagnosis. No cancers in patients <50 years of age were microsatellite unstable compared with 91 (23.6%) of 346 for those >50 years of age. No young cancers contained a BRAF mutation compared with 46 (10.6%) of 434 in older cancers (p < 0.001). KRAS mutations were less common in young cancers compared with older cancers (13/57 (22.8%) vs 126/410 (30.7%); p < 0.01). Eleven (19.3%) of 57 young cancers were proximal compared with 228 (51.8%) of 440 (p < 0.001) older cancers.
This study was limited by its retrospective design.
The lack of CpG island methylator phenotype tumors in young patients is consistent with the dominant left-sided cancer distribution seen in the young and focuses efforts to understand and prevent cancer in this age group on causes of chromosomal instability. See Video Abstract at http://links.lww.com/DCR/A709.
1 Department of Colorectal Surgery, Cleveland Clinic, Cleveland, Ohio
2 Sanford R. Weiss, M.D., Center for Hereditary Colorectal Neoplasia, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, Ohio
3 Department of Stem Cell and Regenerative Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
Funding/Support: None reported.
Financial Disclosure: None reported.
Podium presentation at the meeting of The American Society of Colon and Rectal Surgeons, Nashville, TN, May 19 to 23, 2018.
Correspondence: Hanumant Chouhan, M.D., Department of Colorectal Surgery, Cleveland Clinic, 9500 Euclid Ave, A30, Cleveland, OH 44195. E-mail: firstname.lastname@example.org