• Department of Gastrointestinal, Bariatric and Metabolic Surgery, Research Center for Nutrition, Metabolism and Food Safety, West China-PUMC C.C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
• Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.

OBJECTIVE: To clarify the inconsistent findings of epidemiological studies on the association between dietary garlic consumption and colorectal cancer (CRC) incidence, by prospectively assessing the association in a large US population.

METHODS: Data of 58,508 participants (aged 55-74) from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial were analyzed. Dietary data were collected using a validated questionnaire. Multivariable Cox regression analysis determined hazard ratio (HR) and 95% confidence interval (CI). Restricted cubic spline regression was used to investigate the non-linear relationship, and subgroup analysis was conducted to examine potential effect modifiers.

RESULTS: During a median follow-up of 12.05 years, 782 CRC cases were documented, including 456 proximal colon cancer cases, 322 distal CRC cases, and 4 CRC cases with an unknown site. Moderate dietary garlic consumption was significantly associated with a reduced risk of overall CRC (HR_{quintile 3vs. 1}: 0.70, 95% CI: 0.54 to 0.91, p = 0.007, P for trend: 0.434), exhibiting a U-shaped dose-response pattern, and also with overall CRC in males in the stratified Cox regression model (Model 2: HR_{quintile 3vs. 1}: 0.57, 95% CI: 0.40 to 0.81, p = 0.002), but not in females. The protective association was more pronounced in men, Caucasian, and those with lower alcohol consumption. Notably, these protective effects were observed for overall distal CRC (HR_{quintile 3vs. 1}: 0.62, 95% CI: 0.42 to 0.93, p = 0.021; and HR_{quintile 4vs. 1}: 0.63, 95% CI: 0.43 to 0.92, p = 0.018, P for trend: 0.208); and for distal CRC in males (HR_{quintile 3vs. 1}: 0.40, 95% CI: 0.22 to 0.71, p = 0.002, P for trend: 0.696), but not for proximal CRC.

CONCLUSION: Moderate consumption of dietary garlic is associated with a decreased CRC risk in the US population, with variations based on CRC anatomic subsites. Further in-depth prospective studies are needed to validate these findings in different populations and to explore subsites-specific associations.