Being overweight increases the risk of colorectal cancer by 25–57%

Colorectal cancer (CRC) remains one of the leading causes of cancer morbidity and mortality worldwide. Along with genetic and environmental factors, overweight and obesity have long been considered significant determinants of increased risk of CRC. However, large enough pooled analyses have not yet been conducted to accurately assess the magnitude of this influence. The study is published in the journal GeroScience.

Research methods

The authors conducted a systematic review and meta-analysis of 66 studies (52 cohort and 14 case-control studies) involving more than 83 million patients in cohort studies and almost 237 thousand participants in case-control studies. The literature search covered publications from 1992 to 2024 in the PubMed, CENTRAL, and Web of Science databases. Risk pooling was performed using the random effects model with the calculation of pooled hazard ratios (HR) and 95% confidence intervals (CI). Forest and funnel plots were used for visualization, as well as Z-plots to assess the sufficiency of the data volume.

Mechanisms and implications

• Chronic inflammation: Obesity is associated with the production of proinflammatory cytokines that promote mutation of colonic epithelial cells.
• Insulin resistance and IGF-1: High IGF-1 stimulates cell proliferation and reduces apoptosis, accelerating carcinogenesis.
• Microbiota: Excess weight changes the composition of intestinal bacteria, increasing the production of carcinogenic secondary bile acids.

"This is the largest analysis to date that shows that obesity is a powerful and reversible risk factor for colorectal cancer," said lead author Zoltan Ungvari.

Key Results

• Overall effect of obesity: pooled HR = 1.36 (95% CI 1.24–1.48; p < 0.01), corresponding to a 36% increase in CRC risk.
• Gender differences: in men HR = 1.57 (95% CI 1.38–1.78; p = 0.01) — a 57% increase in risk, in women HR = 1.25 (95% CI 1.14–1.38; p < 0.01) — a 25% increase in risk.
• Case-control studies showed a similar trend, but with marginal significance (HR = 1.27; 95% CI 0.98–1.65; p = 0.07).
• Heterogeneity: Statistically significant variability between studies in all analyses indicates the influence of study design and population characteristics on risk estimates.

Interpretation and clinical conclusions

1. Overweight is an independent risk factor for CRC. The results confirm the need for active measures to reduce obesity in the population to prevent CRC.
2. Increased vulnerability in men. Men show a more pronounced increase in risk, which may be related to the distribution of fat tissue and hormonal factors.
3. Public health and screening. In regions with a high prevalence of overweight and obesity, it is advisable to expand CRC screening programs and implement preventive programs of healthy nutrition and physical activity.

Recommendations for health care

• BMI control: Even a 5–10% weight loss can significantly reduce the risk of CRC.
• Diet and activity: Promote a Mediterranean diet rich in fiber and regular physical activity.
• Screening: Obese patients should start colonoscopy earlier - at 45 instead of 50, according to new guidelines.

Authors' comments

• Zoltan Ungvari: "Our meta-analysis provides compelling evidence that excess body weight significantly increases the risk of colorectal cancer, especially in men. These data should be a driver for public programs to combat obesity."
• Mónika Fekete: “Although different study designs introduce heterogeneity, the overall trend remains the same: reducing obesity in the population can significantly reduce the burden of CRC.”
• Balázs Győrffy: “Further study of the mechanisms of sex differences is needed to understand which biological processes make men more vulnerable to the carcinogenic effects of obesity.”