Molecular and Clinicopathological Differences by Age at the Diagnosis of Colorectal Cancer

Abstract

We compared the clinicopathological and molecular profiles between different age groups of sporadic colorectal cancer (CRC) patients (age <50, 56–60, 60–70, 70–80, and >80); 1475 CRC patients were enrolled after excluding 30 individuals with Lynch syndrome. The mutation spectra for APC, TP53, KRAS, PIK3CA, FBXW7, BRAF, NRAS, HRAS, TGFbR, Akt1, and PTEN were analyzed using polymerase chain reaction (PCR), followed by MassArray and microsatellite (MSI-high) analysis by performing genotyping. Male patients (74.1%) were significantly predominant to females (25.9%) in the older age group (70–80, >80). There was an insignificantly linear trend between TNM staging and age-onset of CRC diagnosis. Patients aged < 50 had 58.7% diseases in the advanced stages (Stage III: 36.5% and IV: 22.2% respectively), while this decreased to 40.2% (Stage III: 26.2% and IV; 14.0% respectively) in patients >80. The distributions of mutation frequency were similar in majority of the genes studied among different age groups. Additionally, patients aged <50 had significantly higher frequency of MSI-high, PTEN, and HRAS mutations than those of other groups. Age-onset at diagnosis significantly affected overall survival (HR = 1.46; 95% CI: 1.35–1.58), but not cancer-specific survival (HR = 1.08; 95% CI: 0.99–1.18) in multivariate analysis. In conclusion, molecular and clinicopathological differences were not as significant among different age groups of CRC patients as previously suspected.

Keywords

• colorectal cancer
• mutation
• p53
• APC
• MSI
• PI3K