International audience ; Background: Energy restriction during childhood and adolescence is suggested to lower colorectal cancer (CRC) risk. We investigated this in the Netherlands Cohort Study. Methods: Information on diet and other risk factors was collected by a baseline questionnaire in 1986 when cohort members were 55-69 years of age (n=120,852). Three indicators of early life exposure to energy restriction were assessed: father's employment status during the Economic Depression (1932-40), and place of residence during World War 2 years (1940-44) and the 'Hunger Winter' (1944-45); a severe famine. Using the case-cohort approach, incidence rate ratios (RR) and 95% confidence intervals (CI) were calculated for total colorectal, proximal colon, distal colon, rectosigmoid, and rectal cancers, according to the three time periods of energy restriction. After 16.3 years of follow-up, 2573 cases were available for multivariate analyses. Results: Men who lived in a western city during the Hunger Winter and therefore exposed to the highest degree of energy restriction, had a statistically significant lower risk of developing CRC (RR: 0.77, 95% CI: 0.63-0.94), and tumors of the proximal colon (RR: 0.68, 95% CI: 0.49-0.94) and rectum (RR: 0.66, 95% CI: 0.47-0.92). In women, non-statistically significant inverse associations were observed for tumors of the distal colon, rectosigmoid, and rectum. Inverse associations were also observed between the other two exposure times and studied endpoints, though not statistically significant. Conclusions: This unique observational evidence suggests that severe energy restriction during childhood and adolescence may lower CRC risk, especially in men, thus providing insight regarding the role of energy intake during early life in CRC development.