Heme iron intake and the risk of colorectal cancer: a prospective analysis of the modifying role of calcium.

PURPOSE: Although red meat and processed meat are well-established risk factors of colorectal cancer (CRC), the mechanisms underlying this association are less clear. Heme iron, abundant in red and processed meats, is one plausible etiologic factor. In addition, calcium, a well-established independent protective factor against CRC, may prevent heme-induced colorectal carcinogenesis by binding to heme iron in the gut.

METHODS

We prospectively examined the association between heme iron and CRC risk and whether these associations differed by calcium intake in the Nurses' Health Study, Nurses' Health Study II and Health Professionals Follow-Up Study. We used Cox proportional hazards regression analyses to calculate cohort-specific hazard ratios (HRs) and pooled results using a fixed-effect model.

RESULTS

We analyzed data from 211,851 participants and documented 2983 incident CRC cases during up to 36 years of follow-up. Comparing the highest to lowest quintile, the pooled multivariable HRs (95% CIs) for CRC were 1.03 (0.91, 1.17) for total heme iron intake, 1.02 (0.91, 1.16) for heme iron from red and processed meat, and 1.02 (0.90, 1.15) for heme iron from non-red and non-processed meat sources. Total heme iron intake, heme iron from red and processed meat, and heme iron from non-red meat and non-processed meat sources were largely not associated with CRC risk. Moreover, the association between heme iron and CRC did not appear to differ by calcium status.

CONCLUSION

Overall, our study does not support a strong role of heme iron intake in CRC risk and suggests that the protective association of calcium intake on CRC risk does not depend on heme iron.