We analyzed the association between meat intake, heterocyclic amines (HCAs) and bladder cancer (BC) risk in a large case-control study comprised of 884 BC cases and 878 healthy controls, recruited from 1999 to 2009. Epidemiologic and dietary data were collected via an in-person interview. Compared to the lowest quartile of red meat intake, the odds ratios (ORs) for the second, third and fourth quartiles were 1.17 (95% CI: 0.87-1.58), 1.47 (95% CI: 1.09-1.99) and 1.95 (95% CI: 1.41-2.68), respectively, (p-for trend <0.001). In a subset of participants with intakes of HCAs available, compared with those with the lowest quartile of intake, the ORs for the second, third and fourth quartiles were 1.47 (95% CI: 0.60-3.64), 2.58 (95% CI: 1.09-6.11) and 3.32 (95% CI: 1.37-8.01), respectively, (p for trend <0.001). In cumulative analysis of SNPs in the pathway, compared with subjects carrying 0-4 unfavorable genotypes, subjects carrying 5 and 6 or more unfavorable genotypes were at 1.60-fold (95% CI: 1.20-2.12) and 2.37-fold (95% CI: 1.82-3.10) increased risk, respectively. Moreover, subjects carrying six or more unfavorable genotypes and whose red meat intake was in the highest quartile were at 5.09-fold increased risk (95% CI: 2.89-8.96; p < 0.001). These results strongly support that high red meat intake, high intake of HCAs and carrying high number of unfavorable genotypes in the HCA metabolic pathways are associated with increased risk of BC in the study population.
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