Scientific Study

Background: Recent prospective cohort studies suggest states of energy excess and hyperinsulinemia, including type 2 diabetes (T2D), obesity, sedentary lifestyle, Western pattern diet, increased dietary glycemic load, high intake of sugar-sweetened beverages, and elevated plasma C-peptide are each associated with an increased risk of colon cancer (CC) recurrence and mortality. Conversely, observational studies indicate that increasing nut intake is associated with lower risk of T2D, metabolic syndrome and insulin resistance. However, the effect of nut intake on CC recurrence and survival is unknown. Methods: We conducted a prospective, observational study of 826 patients with stage III CC who reported dietary intake with food frequency questionnaires while enrolled in a randomized adjuvant chemotherapy trial. Using Cox proportional hazards regression, we assessed associations of nut intake with cancer recurrence and mortality. The primary endpoint was disease-free survival (DFS) defined as time from completion of dietary questionnaire following adjuvant therapy to cancer recurrence, death or last follow-up. Results: Compared to patients who abstained from nuts, those who consumed ≥ 2 servings of nuts per week had an adjusted hazard ratio (HR) of 0.58 (95% CI, 0.37 to 0.92; Ptrend = 0.03) for DFS and 0.43 (95% CI, 0.25 to 0.74; Ptrend = 0.01) for overall survival (OS). On subgroup analysis, the significant association was confined to tree-nut intake: HR = 0.54 (95% CI, 0.34 to 0.85; Ptrend = 0.04) for DFS and HR = 0.47 (95% CI, 0.27 to 0.82; Ptrend= 0.04) for OS. There was no significant association between intake of peanut or peanut butter and patient outcome. Association of total nut intake with improved outcomes was maintained across other known or suspected predictors of recurrence and mortality, including across common genomic alterations (microsatellite instability, KRAS mutation, BRAF mutation, and PIK3CA mutation). Conclusions: Higher consumption of nuts may be associated with significantly reduced cancer recurrence and death in patients with stage III CC. Support: U10CA180821, U10CA180882, Pfizer. Clinical trial information: NCT00003835.