Nut and peanut butter intake and the risk of colorectal cancer and its anatomical and molecular subtypes: the Netherlands Cohort Study.

Nut intake has been associated with reduced total cancer-related mortality, but evidence for colorectal cancer (CRC) risk is inconclusive. We investigated the associations between nut and peanut butter intake and anatomical CRC subtypes. To account for molecular heterogeneity, associations between nut and peanut butter intake and colorectal tumors harboring APC, KRAS or BRAF mutations, p53 overexpression or microsatellite instability were examined in secondary analyses. In the Netherlands Cohort Study (n = 120 852), lifestyle habits were measured with a questionnaire in 1986. After 20.3 years follow-up, 3567 CRC cases were included in case-cohort analyses. For the analyses of molecular CRC subtypes, 574 cases were included after 7.3 years follow-up. In categorical analyses, total nut intake was not significantly associated with CRC [HR (95% CI) 10+ g/day versus non-consumers = 0.94(0.78-1.15) in men; 0.96(0.75-1.22) in women]. In restricted cubic spline analyses, significant non-linear inverse associations with rectal cancer were observed for total nut, peanut and peanut butter intake in women, and borderline significant non-linear inverse associations for total nut and peanut intake in men. Regarding the molecular CRC subtypes, peanut butter intake was significantly associated with an increased risk of colorectal tumors that did not develop through the serrated neoplasia pathway in men [HR (95% CI) per 5 g/day increment = 1.22(1.07-1.38)]. Nut and peanut butter intake are non-linearly inversely associated with rectal cancer risk in women. In men, nut intake is borderline significantly non-linearly associated with a reduced rectal cancer risk. Peanut butter is associated with an increased risk of colorectal tumors that do not develop through the serrated neoplasia pathway in men.