Carcinogenesis. 2020 Jul 30:bgaa080. doi: 10.1093/carcin/bgaa080. Online ahead of print.
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 NLCS (n=120852),
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 nonconsumers=0.94(0.78-1.15) in men; 0.96(0.75-1.22) in women). In restricted cubic spline analyses, significant nonlinear inverse associations with rectal cancer were observed for total nut, peanut, and peanut butter intake in women, and borderline significant nonlinear 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 nonlinearly inversely associated with rectal cancer risk in women. In men, nut intake is borderline significantly nonlinearly 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.