Adherence to the Paleolithic diet and Paleolithic-like lifestyle reduce the risk of colorectal cancer in the United States: a prospective cohort study

BACKGROUND: The plant-based paleolithic diet (PD) and the paleolithic-like lifestyle (PLL) may reduce the risk of chronic diseases, including colorectal adenomas. These dietary and lifestyle approaches are proposed to exert their effects through mechanisms such as reducing inflammation, oxidative stress, and insulin levels. However, whether PD and PLL is associated with the risk of colorectal cancer (CRC) has not been determined. METHODS: A cohort of 74,721 individuals who participated in the PLCO study were included in this analysis. Adherence to the PD and PLL was assessed using PD and PLL scores, where higher scores indicated greater adherence. Multivariable Cox models were utilized to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of CRC and its subsites (proximal colon cancer and distal CRC). Subgroup analyses were conducted to identify potential effect modifiers. RESULTS: During a mean follow-up of 9.2 years, a total of 694 CRC cases were identified. Participants in the highest compared with the lowest quartiles of PD score had a lower risk of CRC (Q4 vs Q1: HR 0.76, 95% CI 0.61–0.95, P(trend) = 0.009) and proximal colon cancer (Q4 vs Q1: HR 0.73, 95% CI 0.55–0.97, P(trend) = 0.02). A stronger inverse association was observed for PLL score with the risk of CRC (Q4 vs Q1: HR 0.64, 95% CI 0.51–0.81, P(trend) < 0.001), proximal colon (Q4 vs Q1: HR 0.62, 95% CI 0.46–0.83, P(trend) = 0.001) and distal CRC (Q4 vs Q1: HR 0.69, 95% CI 0.48–0.98, P(trend) = 0.03). Subgroup analyses revealed the inverse association of PD score with the risk of CRC was more pronounced in participants with BMI < 30 (Q4 vs Q1: HR 0.68, 95% CI 0.53–0.87) than in those with BMI ≥ 30 (Q4 vs Q1: HR 1.07, 95% CI 0.68–1.67) (P(interaction) = 0.02). CONCLUSIONS: Our findings suggest that adhering to the PD and PLL could be a new option to reduce CRC risk. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-023-04352-8.