Abstract 165: Predicting risk of colorectal cancer depending on tumor pathology features for first-degree relatives of persons with colorectal cancer.

Abstract

Abstract Background: We hypothesised that colorectal cancer (CRC) risk for relatives of persons diagnosed with CRC could be predicted by tumor molecular pathology features. Methods: We studied a cohort of 5200 first-degree relatives (2550 women) of 792 probands with an incident invasive CRC who were recruited to the Australasian Colorectal Cancer Family Registry via population cancer registries. We excluded 32 families that were known to be Lynch syndrome. For the probands, a standardised tumor morphology review had been conducted; BRAF V600E mutation testing had been performed; and the DNA mismatch repair (MMR) status was determined by microsatellite instability and/or immunohistochemistry for MMR proteins. We calculated standardized incidence ratios (SIR) by comparing the number of CRCs observed in relatives with the number expected based on Australian incidence rates specific for age and sex. We also compared CRC risks for relatives of probands depending on the presence or absence of specific tumor pathology features. Results: We observed 191 CRCs in relatives at mean age at diagnosis of 62.7 (SD 14.3) years and SIR was 2.14 (95% confidence interval, CI 1.85-2.48). Compared with the general population, an increased risk of CRC was observed for relatives of probands with MMR-proficient CRC (SIR 1.98, 95% CI 1.71-2.32), MMR-deficient CRC (SIR 3.60, 95% CI 2.20-6.23), rectal cancer (SIR 1.71, 95% CI 1.36-2.18), distal colon cancer (SIR 2.12, 95% CI 1.63-2.82) and proximal colon cancer (SIR 2.90, 95%CI 2.27-3.75). An increased risk of CRC was observed for relatives of probands with proximal colon cancer compared with rectal cancer (hazard ratio, HR 1.70, 95% CI 1.21-2.39, p=0.002) and for relatives of probands with MMR-deficient CRC compared with MMR-proficient CRC (HR 1.84, 95% CI 1.09-3.12, p=0.02). There was no evidence of increased risk of CRC for relatives of probands with other pathology features of CRC (tumor grade, margin, peritumoral lymphocytes, tumor infiltrating lymphocytes, Crohn-like reactions, venous invasion, BRAF mutation and contiguous adenoma) compared with those without these features. Conclusions: First-degree relatives of persons with MMR-deficient CRC (not caused by Lynch syndrome) have a higher risk of CRC compared with first-degree relatives of persons with MMR-proficient CRC. Citation Format: Aung K. Win, Daniel D. Buchanan, Christophe Rosty, Graham G. Giles, John L. Hopper, Mark A. Jenkins. Predicting risk of colorectal cancer depending on tumor pathology features for first-degree relatives of persons with colorectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 165. doi:10.1158/1538-7445.AM2013-165