Table 1. Summary of evidence and mechanisms relating nutrients and foods to colorectal cancer.

Nutrient or Food	Level of Evidencea	Estimate of Relative Risk (RR)b	Proposed Mechanisms
Nutrient
Calcium	Probable	RR=0.92 (0.89–0.95) per 300 mg/day increase of total calcium intake [ref 74]	Binding to fatty acids and free bile acids; suppression of cell proliferation; promotion of cell differentiation and apoptosis; inhibition of oxidative DNA damage; modulation of colorectal cancer-related cell signaling pathways
Vitamin D	Limited-suggestive	RR=0.95 (0.93–0.98) per 100 IU/day increase of dietary vitamin D intake; 0.96 (0.94–0.97) per 2.5 ng/mL (6.25 nmol/L) increase of circulating 25(OH)D [ref 7]	Anti-proliferation, pro-differentiation and apoptosis, anti-inflammation, inhibition of invasion and metastasis, and suppression of angiogenesis
Fiber	Convincing	RR=0.90 (0.86–0.94) per 10 g/day increase of dietary fiber intake [ref131]	Increased stool weight, decreased transit time, dilution of colonic carcinogenic content, decreased adiposity, and anticancer properties of short-chain fatty acids produced by bacterial fermentation of resistant starch
Folate	Limited-suggestive	RR=0.99 (0.93–1.05) per 100 μg/d increase of dietary folate intake; 0.98 (0.94–1.03) per 100μg/day increase of total folate intake [ref 7]	Essential nutrient for DNA methylation and DNA synthesis, critical processes in carcinogenesis
Vitamin B6	N/A	RR=0.90 (0.75–1.07) comparing the highest to the lowest categories of vitamin B6 intake; 0.51 (0.38–0.69) per 100 pmol/mL increase of blood level of pyridoxal 5′-phosphate [ref 218]	One-carbon metabolism, critical for DNA synthesis and DNA methylation
Methionine	N/A	RR=0.89 (0.79–1.00) comparing the highest to the lowest categories [ref 228]	One-carbon metabolism, critical for DNA synthesis and DNA methylation; inhibition of cell growth and reduced inflammation
Vitamin A, C, E	Limited-no conclusion	RR=0.93 (0.79–1.10) for total vitamin A, 0.86 (0.74–1.00) for total vitamin C and 0.83 (0.70–0.99) for total vitamin E, comparing the highest to the lowest categories [ref 255]	Antioxidative, inhibition of cell proliferation, pro-apoptosis, and reduced inflammation
Selenium	Limited-no conclusion	RR=0.81 (0.71–0.92) comparing the highest to the lowest categories of selenium concentrations in serum, plasma or toenails [ref 253]	Antioxidative, inhibition of cell proliferation, pro-apoptosis, and reduced inflammation
Total fat	Limited-no conclusion	RR=0.99 (0.89–1.09) comparing the highest to the lowest categories [ref 307]	Increased intestinal level of bile acids, which can be metabolized by bacteria to deoxycholic acid to promote CRC development
Omega-3 polyunsaturated fatty acids	Limited-no conclusion	RR=0.97 (0.86–1.10) comparing the highest to the lowest categories [ref 314]	Reduced inflammation through inhibition of arachidonic acid-derived eicosanoid biosynthesis, and modulation of transcription factor activity, gene expression and signal transduction; improved insulin sensitivity; altered cell membrane fluidity
Food
Red and processed meat	Convincing	RR=1.16 (1.04–1.30) per 100 g/day increase of red and processed meat intake [ref 7]	Carcinogenic effect of heme iron, N-nitro compounds, and heterocyclic amines generated during cooking at high temperature. Pro-neoplastic effect of increased adiposity and insulin
Milk	Probable	RR=0.91 (0.85–0.94) per 200 g/day increase of total milk intake [ref 419]	Antineoplastic effect of calcium, vitamin D (for fortified milk), conjugated linoleic acid, butyric acid, and lactose
Fruits	Limited-suggestive	RR=0.97 (0.94–0.99) per 100 g/day increase of fruit intake [ref 7]	Anticarcinogenic compounds, such as folate, vitamins, fiber, minerals, and flavonoids; decreased adiposity
Non-starchy vegetables	Limited-suggestive	RR=0.98 (0.96–0.99) per 100 g/day increase of vegetable intake [ref 7]	Anticarcinogenic compounds, such as folate, vitamins, fiber, minerals, flavonoids, and glucosinolates contained in cruciferous vegetables; decreased adiposity
Whole grains	Convincing	RR=0.83 (0.78–0.89) per 3 servings/day increase of whole grains [ref 131]	Anticancer properties of fiber, antioxidants and phytochemicals; decreased adiposity; improved insulin sensitivity and decreased insulin level

^aSource: Continuous Update Project Report on Food, Nutrition, Physical Activity, and the Prevention of Colorectal Cancer, World Cancer Research Fund/American Institute for Cancer Research, 2011⁷.

^bThe estimates are derived from the 2011 review by World Cancer Research Fund/American Institute for Cancer Research⁷, except for the nutrients that were not covered in that review (i.e., vitamin B6, methionine, total fat, and omega-3 polyunsaturated fatty acids), nutrients for which observational studies were not summarized in that review (i.e., vitamins A, C and E, and selenium), and exposures for which more recent meta-analyses were available (i.e., calcium, fiber, milk, and whole grain).