Diet, dairy, and colorectal cancer risk: A 2025 landmark study summary

Advancing our understanding of cancer’s etiology, particularly its links to diet, is vital for developing more effective prevention and early intervention strategies. Despite being the 3^rd most common cancer worldwide, there remains an important gap in understanding how different foods influence the risk of colorectal cancer.

In response to this research gap, a prospective study, including 542,778 women (with a mean age of 56 ±6 years) in the UK, systematically analyzed 97 dietary factors in relation to colorectal cancer risk. ¹ The participants were followed for an average of 16.6 years (± 4.8), during which 12,251 women developed colorectal cancer. Participants completed a detailed dietary questionnaire among which about 37,994 participants (approx. 7%) provided at least one additional 24hr dietary assessment. Parallel to this, a Mendelian randomisation analysis of milk intake was conducted using data from a range of international registries, such as the ColoRectal Transdisciplinary Study, the Colon Cancer Family Registry, and the Genetics and Epidemiology of Colorectal Cancer consortium (GECCO). Mendelian randomization is a research method that uses genetic variants to assess whether a relationship between a risk factor and an outcome is causal.

Out of the 97 studied dietary factors, 17 were associated with the risk of colorectal cancer.

Dietary factors linked to decreased risk of colorectal cancer

Calcium and dairy products

Among the strongest associations observed, calcium was strongly linked to a lower colorectal cancer risk; a 17% lower risk was observed per 300mg/day of calcium intake. Similarly, a 14% lower risk of colorectal cancer was observed per 200g/d of milk consumption. These findings were further supported by the Mendelian randomisation analysis, which linked an intake of 200 g/day of milk to a:

• 40% reduction in colorectal and colon cancer risk;
• 51% reduction in rectal cancer risk.

This finding is particularly impactful as the Mendelian randomization method is often used to detect a causal relationship and better captures long-term effects and habits, whereas reported intake reflects short-term dietary habits.

Beneficial inverse associations were also observed with other dairy products, such as yogurt and nutrients commonly present in dairy products (e.g., riboflavin, phosphorus, potassium, and magnesium). Further analysis revealed that calcium intake was independently associated with decreased colorectal cancer risk, which suggests that calcium plays a role in dairy’s protective effect in colorectal cancer prevention. In addition, although both dairy and non-dairy calcium sources were linked to a reduced risk, dairy sources demonstrated a stronger, statistically significant reduction in colorectal cancer risk. This underscores the importance of considering the dairy matrix in understanding dairy’s protective role. The effects of calcium supplements alone were not assessed in this study.

Overall, these findings reinforce the position of the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research, which indicate a probable strong protective role of dairy products in reducing the risk of colorectal cancer.²

Potential mechanisms

Several mechanisms have been attributed to calcium’s protective effects on colorectal cancer risk:

• Binding to free fatty acids and bile acids in the colon, thereby reducing their potential carcinogenic effects;
• Decreasing colonic permeability and protecting the intestinal lining from damage by luminal content such as bile acids;
• Promoting epithelial cell differentiation in the colon;
• Reducing DNA oxidative damage;
• Enhancing apoptosis.

Beyond calcium, other compounds that make up the dairy matrix, including riboflavin, phosphorus, potassium, magnesium, conjugated linoleic acid, butyric acid, and sphingomyelin, may also contribute to its protective effects. More specifically, the latter 3 have been shown to inhibit chemically induced colon carcinogenesis in animal models.

Other dietary factors and their potential mechanisms

There was a modest association observed between higher intakes of breakfast cereals, fruits, whole grains, carbohydrates, fibre, total sugars, folate, and vitamin C and reduced risk of colorectal cancer. However, the authors note that many of these associations may have been influenced by other lifestyle and dietary factors.

It is hypothesized that whole grains and dietary fibre notably play a significant role in many of the protective effects listed above. Whole grains, which are high in fibre, may reduce colorectal cancer risk by bulking up the stool, thereby shortening transit time, and diluting carcinogens in the colon. Additionally, dietary fibre fermentation produces short-chain fatty acids in the colon, which lowers intestinal pH and reduces cell proliferation by inhibiting bile acid conversion.

Dietary factors linked to increased risk of colorectal cancer

Processed and red meat and potential mechanisms

Processed and red meat consumption was linked to a higher colorectal cancer risk, with an 8% increased risk per 30g/day increased intake. This is notably higher than the 12% increase in risk per 100g/day observed in the 2018 WCRF meta-analysis.³ While both red and processed meats both showed positive associations with colorectal cancer risk, the authors observe that processed meats demonstrated a larger positive association. This is also reflected in the WCRF’s recommendation for moderate red meat consumption (350-500g cooked red meat/week), and opting for leaner cuts of meat as part of a healthy, balanced diet.⁴

The authors note that this positive association may be driven by the presence of heme iron, which can catalyze the formation of N-nitroso compounds that may induce mutations in the colon. Additionally, other potential factors include cooking meat at high temperatures, which produces heterocyclic amines and polycyclic aromatic hydrocarbons, smoking meat, and the use of sodium nitrites/nitrates for preservation which may lead to the formation of exogenous N-nitroso compounds.

Alcohol and potential mechanisms

Among the strongest associations observed, alcohol was positively linked to colorectal cancer risk. The study findings reveal a 15% increased risk of colorectal cancer per 20 grams of alcohol consumed per day, which is in line with the findings from the 2018 WCRF dose-response meta-analysis and many Mendelian randomisation studies conducted on adults of Asian and European ancestry.^3,5-7

It is speculated that the production of acetaldehyde, a byproduct that is mutagenic at high concentrations, may disturb deoxyribonucleic (DNA) repair in human tissue and animal studies, as well as increase production of carcinogenic reactive oxygen species.

While the authors acknowledge some limitations, such as the lack of generalizability beyond middle-aged women of European ancestry and the inability to examine specific food products, this landmark study further supports existing well-established evidence revealing the protective effects of dairy on colorectal cancer risk.