Jason A Zell1, Bruce S Lin2, Argyrios Ziogas3, Hoda Anton-Culver3
1Department of Epidemiology; Genetic Epidemiology Research Institute; Chao Family Comprehensive Cancer Center and Department of Medicine, Division of Hematology/Oncology, University of California, Irvine, California, USA.
2Chao Family Comprehensive Cancer Center; Department of Medicine, Division of Hematology/Oncology, University of California, Irvine, California, USA.
3Department of Epidemiology; Genetic Epidemiology Research Institute, University of California, Irvine, California, USA.
DOI:10.4103/1477-3163.104004
ABSTRACT
Background: Dietary arginine and meat consumption are implicated in colorectal cancer (CRC) progression via polyamine-dependent processes. Polymorphism in the polyamine-regulatory gene, ornithine decarboxylase 1 (Odc1, rs2302615) is prognostic for CRC-specific mortality. Here, we examined joint effects of meat consumption and Odc1 polymorphism on CRC-specific mortality. Materials and Methods: The analytic cohort was comprised of 329 incident stage I-III CRC cases diagnosed 1994-1996 with follow- up through March 2008. Odc1 genotyping was conducted using primers that amplify a 172-bp fragment containing the polymorphic base at +316. Dietary questionnaires were administered at cohort entry. Multivariate Cox proportional hazards regression analysis for CRC-specific mortality was stratified by tumor, node, metastasis (TNM) stage, and adjusted for clinically relevant variables, plus meat consumption (as a continuous variable, i.e., the number of medium-sized servings/week), Odc1 genotype, and a term representing the meat consumption and Odc1 genotype interaction. The primary outcome was the interaction of Odc1 and meat intake on CRC-specific mortality, as assessed by departures from multiplicative joint effects. Results: Odc1 genotype distribution was 51% GG, 49% GA/AA. In the multivariate model, there was a significant interaction between meat consumption and Odc1 genotype, P-int = 0.01. Among Odc1 GA/AA CRC cases in meat consumption Quartiles 1-3, increased mortality risk was observed when compared to GG cases (adjusted hazards ratio (HR) = 7.06 [95% CI 2.34-21.28]) – a difference not found among cases in the highest dietary meat consumption Quartile 4. Conclusions: Effects of meat consumption on CRC-specific mortality risk differ based on genetic polymorphism at Odc1. These results provide further evidence that polyamine metabolism and its modulation by dietary factors such as meat may have relevance to CRC outcomes.
Keywords: Colorectal cancer, meat consumption, mortality, ornithine decarboxylase, ornithine decarboxylase l, polyamines, single nucleotide polymorphism