Dietary nitrosyl-heme from processed meats and its association with colorectal cancer risk: findings from the EPIC cohort study

Background: Processed meat (PM) consumption is an established risk factor for colorectal cancer (CRC). It has been hypothesized that nitrosyl-heme, formed by the addition of nitrites during meat processing, may enhance the carcinogenic effects of PMs. This study aims to investigate the association between nitrosyl-heme intake and CRC risk within the European Prospective Investigation into Cancer and Nutrition(EPIC) study. Methods: This prospective study included 367,463 participants(70.3% women) from seven countries from the EPIC-study. Dietary data were collected via baseline questionnaires, and nitrosyl-heme exposure was estimated using biochemical data from 52 Spanish PMs, extrapolated to country-specific items. Sex-specific multivariable-adjusted hazard ratios(HRs) and 95% confidence intervals(CIs) were calculated using Cox proportional hazards models. Results: Over a 15-year median follow-up, 5,115 incident CRC cases were identified. Comparing the highest vs. the lowest sex-specific tertile of nitrosyl-heme intake we found no significant association with CRC risk (HR_T3vsT1:1.01;95%CI:0.93–1.09). Subgroup analyses by tumor subtype and interactions with lifestyle factors also showed no associations. Conclusions: This study offers insights into nitrosyl-heme exposure in European populations but found no link to CRC risk. Further research is needed to understand nitrosyl-heme's role in CRC.