Substitution of dietary protein sources in relation to colorectal cancer risk in the NIH-AARP cohort study

Cancer Causes Control. 2019 Oct;30(10):1127-1135. doi: 10.1007/s10552-019-01210-1. Epub 2019 Jul 20.


Purpose: To evaluate the substitution effect of plant for animal protein with risk of CRC in the large prospective National Institutes of Health-AARP cohort study.

Methods: Protein intake was assessed at baseline using a food frequency questionnaire. HRs and 95% CIs were estimated using multivariable adjusted hazard ratios from Cox proportional hazards models. We used a substitution model with total protein intake held constant, so that an increase in plant protein was offset by an equal decrease in animal protein.

Results: Among 489,625 individuals, we identified 8,995 incident CRCs after a median follow-up of 15.5 years. Substituting plant protein for animal protein was associated with a reduced risk of CRC (HR for highest vs. lowest fifth 0.91; 95% CI 0.83-0.99). This reduction in CRC risk appeared to be primarily due to substituting plant protein for red meat protein (HR 0.89; 95% CI 0.81-0.97), not white meat protein (HR 0.96; 95% CI 0.88-1.05) or other animal protein (HR 0.94; 95% CI 0.86-1.03). When further evaluated by source, reduction in CRC risk was limited to the substitution of protein from bread, cereal, and pasta for red meat protein (HR 0.86; 95% CI 0.80-0.93); this association was stronger for distal colon (HR 0.78; 95% CI 0.67-0.90) and rectal cancer (HR 0.79; 95% CI 0.68-0.91) but null for proximal colon (HR 0.99; 95% CI 0.88-1.11).

Conclusions: This study shows that substituting plant protein for animal protein, especially red meat protein, is associated with a reduced risk of CRC, and suggests that protein source impacts CRC risk.

Keywords: Colorectal cancer; Dietary protein; Plant protein; Prospective cohort study; Protein source.

MeSH terms

  • Aged
  • Animals
  • Colorectal Neoplasms / epidemiology*
  • Female
  • Humans
  • Male
  • Meat Proteins / administration & dosage*
  • Middle Aged
  • National Institutes of Health (U.S.)
  • Plant Proteins, Dietary / administration & dosage*
  • Proportional Hazards Models
  • Prospective Studies
  • Red Meat
  • Risk Factors
  • United States


  • Meat Proteins
  • Plant Proteins, Dietary