Abstract
Previous studies have suggested that deficiencies in mismatch repair genes (dMMR) often occur in patients with colorectal cancer (CRC) and contribute to disease etiology. Here, we looked for a correlation of MMR status to disease outcomes from a large number of Chinese CRC patients stratified by the age of onset of disease. A total of 2233 CRC patients were analyzed and tissue biopsies of surgically removed tumors scored for MMR gene status. The patient distribution after classification consisted of 188 younger aged patients (20–39 years of age), 1024 middle aged patients (40–59 years of age), and 1020 older aged patients (60–85 years of age). In this analysis, the expression of four MMR genes was assessed by immunohistochemistry (IHC). We found that the young group of CRC patients with dMMR had higher overall survival (OS) than the young group of patients with proficient MMR (pMMR) (77% vs. 56%, P = 0.03). Middle‐aged patients with dMMR also had higher OS than middle‐aged group patients with pMMR (78% vs. 68%, P = 0.012). However, we found no statistical difference in OS between dMMR and pMMR status in the older group of patients (75% vs. 71%, P = 0.224). Finally, the middle‐ and older‐aged group set of patients had higher OS than the young group of patients (69% vs. 71% vs. 59%, P = 0.008). These data demonstrated that the age of disease onset can be an important factor to help evaluate the prognosis of CRC when combined with the analysis of MMR status within tumor biopsied tissue.
Highlights
The development of colorectal cancer (CRC) can be a slow process, with early stages of disease often presenting with no clinical symptoms to the patient
We found that gender (HR: 0.96, 95% confidence interval (CI): 0.82–1.11, P = 0.561), tumor location (HR: 0.92, 95% CI: 0.83–1.01, P = 0.064), and pathological differentiation (HR: 0.97, 95% CI: 0.84–1.12, P = 0.700) showed no statistical differences by univariate Cox analysis (P > 0.05) regarding the age of disease onset
When age was analyzed in conjunction with MMR status, we found that younger CRC patients with deficiencies in mismatch repair genes (dMMR) had higher overall survival (OS) than young patients with proficient MMR (77% vs. 56%, HR: 0.42, 95% CI: 0.19–1.02, P = 0.03)
Summary
The development of colorectal cancer (CRC) can be a slow process, with early stages of disease often presenting with no clinical symptoms to the patient. Like many other types of cancer, CRC has been found to have an associated higher incidence with increasing age. The risk of CRC has a marked increase in occurrence after reaching 40 years of age and incidence continues to increase even more rapidly after this age. The risk of CRC doubles with each succeeding decade of age, and continues to rise exponentially in incidence with age [3]. The molecular profiles of CRC patients have been shown to differ between various age groups of patients examined [5,6,7]. Whether patients within these various age groups have a different
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