Red meat intake, NAT2, and risk of colorectal cancer: A pooled analysis of 11 studies
Menée à partir des données de 11 études incluant au total 8 290 patients atteints d'un cancer colorectal et 9 115 témoins, cette étude évalue l'effet d'un polymorphisme génétique associé à l'activité de la N-acétyltransférase 2 sur la relation entre la consommation de viande rouge et le risque de cancer colorectal
Background : Red meat intake has been associated with risk of colorectal cancer (CRC), potentially mediated through heterocyclic amines. The metabolic efficiency of N-acetyltransferase 2 (NAT2) required for the metabolic activation of such amines is influenced by genetic variation. The interaction between red meat intake, NAT2 genotype, and CRC has been inconsistently reported. Methods : We used pooled individual-level data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Red meat intake was collected by each study. We inferred NAT2 phenotype based on polymorphism at rs1495741, highly predictive of enzyme activity. Interaction was assessed using multiplicative interaction terms in multivariate-adjusted models. Results : From 11 studies, 8,290 CRC cases and 9,115 controls were included. The highest quartile of red meat intake was associated with increased risk of CRC compared to the lowest quartile (OR 1.41, 95%CI 1.29 - 1.55). However, a significant association was observed only for studies with retrospective diet data, not for studies with diet prospectively assessed before cancer diagnosis. Combining all studies, high red meat intake was similarly associated with CRC in those with a rapid/intermediate NAT2 genotype (OR 1.38, 95%CI 1.20 - 1.59) as with a slow genotype (OR 1.43, 95%CI 1.28 - 1.61) (p- interaction=0.9). Conclusions : We found that high red meat intake was associated with increased risk of CRC only from retrospective case-control studies and not modified by NAT2 enzyme activity. Impact : Our results suggest no interaction between NAT2 genotype and red-meat intake in mediating risk of CRC.