Nut Consumption and Survival in Patients With Stage III Colon Cancer: Results From CALGB 89803 (Alliance)

Abstract

Purpose Observational studies have reported increased colon cancer recurrence and mortality in patients with states of hyperinsulinemia, including type 2 diabetes, obesity, sedentary lifestyle, and high glycemic load diet. Nut intake has been associated with a lower risk of type 2 diabetes, metabolic syndrome, and insulin resistance. However, the effect of nut intake on colon cancer recurrence and survival is not known. Patients and Methods We conducted a prospective, observational study of 826 eligible patients with stage III colon cancer who reported dietary intake on food frequency questionnaires while enrolled onto a randomized adjuvant chemotherapy trial. Using Cox proportional hazards regression, we assessed associations of nut intake with cancer recurrence and mortality. Results After a median follow-up of 6.5 years, compared with patients who abstained from nuts, individuals who consumed two or more servings of nuts per week experienced an adjusted hazard ratio (HR) for disease-free survival of 0.58 (95% CI, 0.37 to 0.92; P_trend = .03) and an HR for overall survival of 0.43 (95% CI, 0.25 to 0.74; P_trend = .01). In subgroup analysis, the apparent benefit was confined to tree nut intake (HR for disease-free survival, 0.54; 95% CI, 0.34 to 0.85; P_trend = .04; and HR for overall survival, 0.47; 95% CI, 0.27 to 0.82; P_trend = .04). The association of total nut intake with improved outcomes was maintained across other known or suspected risk factors for cancer recurrence and mortality. Conclusion Diets with a higher consumption of nuts may be associated with a significantly reduced incidence of cancer recurrence and death in patients with stage III colon cancer.

Trial registration: ClinicalTrials.gov NCT00003835.

Fig 1.

Derivation of the study cohort. (*) Calorie exclusion: < 600 or > 4,200 calories per day for men and < 500 calories or > 3,500 calories per day for women. Q1, questionnaire 1 (midway through adjuvant therapy); Q2, questionnaire 2 (6 months after completion of adjuvant therapy). CALGB, Cancer and Leukemia Group B.

Fig 2.

Multivariable hazard ratios (HRs) and 95% CIs for cancer recurrence or mortality across strata of various factors. The analyses used five categories of total nut intake (never, less than one serving per month, one to three servings per month, one serving per week, and two or more servings per week). The forest plot represents the HRs of the comparison of never nut consumers versus consumers of two or more servings of nuts per week, adjusting for calorie intake, age, sex, depth of invasion through bowel wall, number of positive lymph nodes, baseline performance status, treatment group, body mass index, physical activity, aspirin use, and glycemic load. P values are two-sided; P_inter indicates P for interaction between strata and nut intake; P_trend indicates P for trend across levels of nut intake. COX2, cyclooxygenase-2; CPT-11, irinotecan; FU, fluorouracil; LV, leucovorin; MET-h/wk, metabolic equivalent task hours per week.

Fig A1.

Kaplan-Meier curves for disease-free survival (DFS) by total nut consumption. Curves depict survival for five categories of total nut intake (never, less than one serving per month, one to three servings per month, one serving per week, and two or more servings per week).

Fig A2.

Kaplan-Meier curves for recurrence-free survival (RFS) by total nut consumption. Curves depict survival for five categories of total nut intake (never, less than one serving per month, one to three servings per month, one serving per week, and two or more servings per week).

Fig A3.

Kaplan-Meier curves for overall survival (OS) by total nut consumption. Curves depict survival for five categories of total nut intake (never, less than one serving per month, one to three servings per month, one serving per week, and two or more servings per week).