Anatomical subsite can modify the association between meat and meat compounds and risk of colorectal adenocarcinoma: Findings from three large US cohorts.

Distal and proximal colon tumors have distinct incidence trends and embryonic origins; whether these sub-sites have distinct susceptibilities to known risk factors is unclear. We used pooled data from 407,270 participants in three US-based studies, with overall median follow-up of 13.8 years. We used adjusted Cox models to analyze the association between dietary intakes (from diet history questionnaire) of total, processed and unprocessed red meat; total white meat, poultry and fish and meat-related compounds: heme iron, nitrate, nitrite, the heterocyclic amines (HCAs) and benzo(a)pyrene (B(a)P) and incidence of colorectal cancer subsites. The risk of colorectal cancer (n = 6,640) increased by 35% for each 50 g/1,000 kcal higher daily intake of total red meat, with a significant right-to-left trend from proximal colon (HR: 1.24; 95% CI: 1.09-1.39) to distal colon (HR: 1.34; 95% CI: 1.13-1.55) and rectum (HR: 1.53; 95% CI: 1.28-1.79). Only unprocessed red meat showed a significant right-to-left trend. Each 50 g/1,000 kcal increase in white meat intake was associated with a 26% reduction in total colorectal cancer risk (HR: 0.74; 95% CI: 0.68-0.80), with a significant inverse right-to-left trend. The highest quintile of heme iron was associated with increased cancer risk only in the distal colon (HR: 1.20; 95% CI: 1.02-1.42) and rectum (HR: 1.27; 95% CI: 1.07-1.52). The highest quintile of HCAs, and nitrate/nitrite were associated with increased risk of total colorectal cancer, but these associations did not vary across anatomical subsites. In summary, right and left subsites of the colon may have distinct susceptibilities to meat and possibly other dietary risk factors, suggesting that the causes of colorectal cancer may vary across anatomical subsites.