Abstract 637: Dietary heme iron and risk of colorectal cancer with specific mutations in colorectal cancer key genes

Abstract

Background: Red meat intake has been linked to increased colorectal cancer risk but the underlying mechanisms remain unclear. Experimental studies suggest a role for dietary heme, but epidemiological evidence for its carcinogenic potential is inconclusive. Because heme may promote specific mutations, it could be insightful to link heme exposure data to colorectal cancer (CRC) with such mutations in key genes in an observational, population-based study. Methods: We investigated the association between dietary heme iron intake (tertiles) and CRC cancer with adenomatous polyposis coli (APC) and Kirsten ras (KRAS) mutations, and tumor protein 53 (TP53) overexpression, in the Netherlands Cohort Study. After 7.3 yrs of follow-up, excluding the first 2.3 years, adjusted rate ratios (RR) and 95% confidence intervals (CI) were calculated, using 3,949 subcohort members (aged 55-69 years at baseline) and 733 CRC patients. Results: Heme iron intake was associated with an increased risk of CRC with activating G>A mutations in KRAS (RR=2.14 for the highest compared to the lowest intake; 95% CI: 1.17, 3.92; Ptrend = 0.01). In addition, a positive association between heme intake and the risk of overall G>A mutations in APC tumors was observed (RR=1.73 for the highest compared to the lowest intake; 95% CI: 1.18, 2.54; Ptrend = 0.005). However, this association was not found when restricting our analyses to CRC harboring G>A mutations leading to a truncated APC (RR=1.35 for the highest compared to the lowest intake; 95% CI: 0.79,2.37; Ptrend = 0.29). Moreover, there was a positive association between heme iron intake and the risk of P53 overexpressed tumors which was not observed in tumours without P53 overexpression (Pheterogeneity = 0.08). Conclusion: These results suggest that heme iron intake is associated with an increased risk of colorectal tumors harboring G>A transitions in KRAS and to a lesser extend in APC, and overexpression of P53. Taking CRC heterogeneity into account contributes to a better molecular understanding of the established association between red meat intake and CRC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 637. doi:1538-7445.AM2012-637