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A Prospective Study of Dietary Folate Intake and Risk of Colorectal Cancer: Modification by Caffeine Intake and Cigarette Smoking

¹ Division of Nutritional Epidemiology, National Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; ² Departments of Nutrition and Epidemiology, Harvard School of Public Health; and ³ Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

Requests for reprints: Susanna C. Larsson, Division of Nutritional Epidemiology, National Institute of Environmental Medicine, Karolinska Institutet, Nobels väg 12, P.O. Box 210, SE-17177 Stockholm, Sweden. Phone: 46-8-52486059; Fax: 46-8-304571. E-mail: susanna.larsson{at}imm.ki.se

Epidemiologic evidence indicates an inverse association of folate intake with risk of colorectal cancer, but whether this association is modified by intake of caffeine (in coffee and tea) or cigarette smoking—factors that possibly interfere with folate—has not been studied. Thus, we examined whether the association between dietary folate intake and incidence of colorectal cancer is modified by caffeine intake and smoking. Cox proportional hazards modeling was used to estimate rate ratios relating dietary folate intake to colorectal cancer incidence among 61,433 women ages 40 to 75 years at recruitment into the Swedish Mammography Cohort in 1987 to 1990. From March 1987 through June 2004, a total of 805 incident cases of colorectal cancer were diagnosed. After controlling for age and other potential confounders, we observed an inverse association between dietary folate intake and risk of colon cancer (rate ratio for the highest versus the lowest quintile, 0.61; 95% confidence interval, 0.41-0.91; P_trend = 0.02), but not of rectal cancer (rate ratio, 0.93; 95% confidence interval, 0.55-1.56; P_trend = 0.97). The inverse association between dietary folate intake and colon cancer risk was most pronounced among smokers (P_interaction = 0.03). We found no apparent modification of risk by caffeine intake. Findings from this population-based cohort study support an inverse association between dietary folate intake and risk of colon cancer and suggest that smokers might benefit most from a high dietary folate intake.

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