Nitrosyl-heme and Heme Iron Intake from Processed Meats and Risk of Colorectal Cancer in the EPIC-Spain Cohort

Background: The International Agency for Research on Cancer classified processed meats (PM) as "carcinogenic" and red meat as "probably carcinogenic" for humans. The possible relationship between colorectal cancer risk and the mechanisms involved in the carcinogenesis of PMs have not been established yet. Nitrosyl-heme and heme iron have been proposed as potential-related compounds. The aim of this study was to determine the association between nitrosyl-heme and heme iron intake and colorectal cancer risk among participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain study.Methods: This prospective study included 38,262 men and women from the EPIC-Spain study. Food consumption was assessed using diet history and food composition tables. Heme iron and nitrosyl-heme intake were determined by estimating the intake of PM items and conducting laboratory analyses. HR estimates were obtained by proportional hazard models, stratified by age at recruitment and study center and adjusted for sex, total energy intake, education, smoking, body mass index, waist size, physical activity, lifetime alcohol, fibre, calcium, and familiar colorectal cancer history.Results: During a mean follow-up of 16.7 years, 577 participants were diagnosed with colorectal cancer. We found no overall association between nitrosyl-heme [HRT3vsT1, 0.98; 95% confidence interval (CI), 0.79-1.21] or heme iron intakes (HRT3vsT1, 0.88; 95% CI, 0.70-1.10) with colorectal cancer risk, nor according to tumor subtypes.Conclusions: Our study found no evidence supporting a link between nitrosyl-heme or heme iron intake and colorectal cancer risk in Spanish subjects.Impact: As research on nitrosyl-heme is preliminary, more heterogeneous studies are necessary to provide more convincing evidence on their role in colorectal cancer carcinogenesis.