Microsatellite Instability and Life Style Factors in Sporadic Colorectal Cancer

Abstract

Background: Colorectal cancer (CRC) in Egypt is a relatively high young onset disease. As a form of heterogeneous cancer, there is interplay between genetic and environmental factors. We aimed at probing the association of life style factors and Microsatellite Instability (MSI) status that could provide more insights on carcinogenic process of CRC. Methods: One hundred incident sporadic CRC patients were involved. Information on risk factors of CRC was obtained and microsatellite instability status was predicted through evaluation of MMR protein expression via immunohistochemistry (IHC). Results: Median age was 47.50 years, females represented 54.0% and 36% of patients were Microsatellite Instability High (MSI-H). Most patients with right sided colon cancer (78.3%) were MSI-H while mostly stable or low MSS/MSI-L for left-sided colon and rectum (78.6%, 74.3% respectively, p<0.001). Patients with low physical activity had higher risk of MSS/MSI-L than those with moderate or high activity p =0.026. Patients with BMI greater than 30 Kg/m 2 had higher MSS/MSI-L (75.5%) than those with BMI between 25-30 Kg/m 2 (60.6%) and those with normal BMI <25 (38.9%), p for trend = 0.006. On subgroup analyses, the association of high BMI with MSS/ MSI-L was only shown in patients younger than 40 years, females, stage III, non-mucin secreting adenocarcinoma and a significant interaction with physical activity. Conclusion: In Conclusion, the present study confirms the increased risk of MSS/MSI-L with increased BMI and speculates this association to be modified by patient's life style and tumor characteristics. Further research is needed to validate present results.

Molecular characterization of colorectal cancer

“…However, the majority of cases are sporadic diseases without a family history of CRC, which is closely associated with microsatellite instability and lifestyle factors. [ 4 5 6 ] Tumor recurrence is the primary barrier to improving overall survival. [ 7 ] To reduce the recurrence rate and mortality of patients with CRC, it is crucial to improve the surveillance ability following surgery.…”

Meta-Analysis of the Association between Dietary Inflammatory Index (DII) and Colorectal Cancer

“…The interplay of modifiable risk factors, such as unhealthy dietary patterns and sedentary lifestyles, have partly contributed to the complexity of obesity to an extent [49]. Several epidemiological evidence have demonstrated that individuals with higher-than-normal BMI are likely to have a higher risk for CRC [8,[49][50][51][52]. In a large, population-based cohort trial, obesity during early adulthood and a constantly increasing BMI throughout the lifespan were significantly associated with CRC [53].…”

“…It is generally believed that long-term exposure to an unhealthy diet, physical inactivity, smoking, and alcohol consumption are all likely to trigger the chronic systemic inflammation, which eventually induces the proliferation of cancer cells [4,5]. Molecular studies also demonstrated that the production of pro-inflammatory cytokines and arrays of free radicals present at cellular levels were attributable to the consumption of an unhealthy diet [6][7][8].…”

Impact of Gene–Environment Interactions on Cancer Development

“…Aberrant DNA methylation in the mismatch repair system (MMR) could bring about an increase in the mutation rate by more than 100-fold compared to normal cells [73]. The immediate consequences are the powerlessness of the genome to faithfully replicate [34,74], and inactivation of genes responsible for MMR, such as MLH1 and MSH2, accounting for between 2-3% of CRC cases [75]. For instance, a twin study from Finland, Denmark, and Sweden found out that 35% of CRC cases were hereditary [76].…”