Biallelic Pms2 Germline Mutations in a Family With a Microsatellite-Stable Brain Tumor and Early Onset Colorectal Cancer

Background: Evidence on the relationship between educational level and colorectal cancer (CRC) risk is inconsistent, with both low and high educational levels having been associated with a risk of developing CRC.Aim: To investigate the relationship between educational level and risk of CRC.Methods: We studied data from 465,785 participants included in the EPIC (European Prospective Investigation into Cancer and Nutrition) study, of whom 2,784 developed CRC during a mean follow-up of 8.7 years.All analyses were adjusted for BMI (Body Mass Index), physical activity, smoking status and duration, dietary intake of energy from fat, energy from non-fat, fibre, fruit, vegetables, red meat, processed meat, alcohol, and of fish.Relative indices of inequality (RIIs) with 95% confidence intervals (95% CIs) for education were estimated using Cox regression models.A RII that is lower than 1 means that CRC risk decreases with decreasing education.We conducted separate analyses for gender, age and geographical region.Results: Relative indices of inequality for education showed that a lower educational level was associated with a lower risk of CRC overall (RII 0.84, 95%CI 0.71-0.99),CRC confined to the colon (RII 0.79, 95%CI 0.64-0.97)and CRC located in the proximal colon (RII 0.66, 95%CI 0.48-0.91).These associations were found in women and subjects younger than 60 years.A clear north-south gradient in risks, with no effect in northern Europe, a statistically not significantly reduced risk in middle European countries and a statistically significant reduced risk in southern Europe was observed for participants with a lower education (RII 0.60, 95%CI 0.42-0.86 for colorectal cancer, RII 0.50, 95%CI 0.33-0.77for colon cancer and RII 0.26, 95%CI 0.13-0.52 for rectal cancer).Despite extensive correction for potential confounders, these estimates remained statistically significant for CRC overall, CRC confined to the colon and proximally located CRC.Conclusions: These findings indicate that persons with a lower educational level have a decreased risk of CRC, This was particularly true for women, subjects younger than 60 years of age and subjects from southern Europe.Further studies in genetic and environmental factors are needed to elucidate the mechanism of this observation.