Abstract
3579 Background: How body size influences risk of molecular subtypes of colorectal cancer (CRC) remains unclear. In this study, we investigated the relationship between height, weight, BMI, WHR and risk of CRC according to expression of beta-catenin, cyclin D1, p53 and microsatellite instability (MSI) status. Methods: Immunohistochemical expression of beta-catenin, cyclin D1, p53 and MSI-screening status was assessed in tissue microarrays with tumours from 584 cases of incident colorectal cancer in the Malmö Diet and Cancer Study. Four anthropometric factors: height, weight, body mass index (BMI), waist- hip ratio (WHR) were categorized by quartiles of baseline anthropometric measurements, and relative risks of CRC according to expression of betacatenin, cyclin D1, p53 and MSI screening status were calculated using multivariate Cox regression models. Results: Expression of cytoplasmatic and nuclear betacatenin, cyclin D1, p53 and MSS all revealed a positive association with increased weight and BMI in the overall analysis. Negative expression of the above mentioned factors was more frequently associated with increased height. MSI was not associated with any of the anthropometric factors in overall analysis and according to gender.Gender specific analysis revealed no association between any anthropometric factors and positive and negative cytoplasmatic beta-catenin expression, beta-catenin nuclear negativity, cyclin D1 negativity and p53 positivity. Nuclear beta-catenin positivity, cyclin D1 positivity, p53 negativity and MSS were all associated with increased weight in women. In men, positive expression of cytoplasmatic and nuclear beta-catenin, cyclin D1 positivity and p53 positivity were all associated with increased WHR. Negative expression of betacatenin was associated with increased weight, while there were no associations between any anthropometric factors and cyclin D1 negativity, MSS or MSI status in men. Conclusions: Findings from this large prospective cohort study demonstrate an association between obesity, measured as weight and BMI, and risk of CRC according to the expression of beta-catenin, cyclin D1, p53 and MSI status.
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