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Randomized Controlled Trial
. 2018 Nov 1;143(9):2261-2270.
doi: 10.1002/ijc.31612. Epub 2018 Aug 7.

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

Arash Etemadi  1 , Christian C Abnet  1 , Barry I Graubard  1 , Laura Beane-Freeman  1 , Neal D Freedman  1 , Linda Liao  1 , Sanford M Dawsey  1 , Rashmi Sinha  1
Affiliations
Randomized Controlled Trial

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

Arash Etemadi et al. Int J Cancer. .

Abstract

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.

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Conflict of interest statement

Conflicts of interest: None

Figures

Figure 1
Figure 1. The association between the intake of different types of A. red meat and B. white meat and colorectal cancer risk by anatomical subsites in the pooled data from the AARP, PLCO and AHS cohorts using substitution models
The point estimates are hazard ratios for highest vs. lowest quintiles of calorie-adjusted intakes, and the lines represent 95% confidence intervals in adjusted Cox models. Detailed results are shown in supplementary table 2. Models are adjusted for sex, age at entry to study, family history of colorectal cancer, ethnicity, regular use of aspirin and other NSAIDS, education, smoking history, body mass index, alcohol consumption, cohort, and daily intakes of fiber, calcium, total energy and total meat.
Figure 2
Figure 2. The association between the intake of meat-associated compounds and colorectal cancer risk by anatomical subsites in the pooled data from the AARP, PLCO and AHS cohorts
The point estimates are Hazard Ratios for highest vs. lowest quintile of calorie-adjusted intakes, and the lines represent 95% CI in adjusted Cox models. Detailed results are shown in supplementary table 3. Models are adjusted for sex, age at entry to study, family history of colorectal cancer, ethnicity, regular use of aspirin and other NSAIDS, education, smoking history, body mass index, alcohol consumption, cohort, and daily intakes of fiber, calcium, and total energy.
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