Pooled analyses of 13 prospective cohort studies on folate intake and colon cancer

Abstract

Objective: Studies of folate intake and colorectal cancer risk have been inconsistent. We examined the relation with colon cancer risk in a series of 13 prospective studies.

Methods: Study- and sex-specific relative risks (RRs) were estimated from the primary data using Cox proportional hazards models and then pooled using a random-effects model.

Results: Among 725,134 participants, 5,720 incident colon cancers were diagnosed during follow-up. The pooled multivariate RRs (95% confidence interval [CI]) comparing the highest vs. lowest quintile of intake were 0.92 (95% CI 0.84-1.00, p-value, test for between-studies heterogeneity = 0.85) for dietary folate and 0.85 (95% CI 0.77-0.95, p-value, test for between-studies heterogeneity = 0.42) for total folate. Results for total folate intake were similar in analyses using absolute intake cutpoints (pooled multivariate RR = 0.87, 95% CI 0.78-0.98, comparing ≥ 560 mcg/days vs. <240 mcg/days, p-value, test for trend = 0.009). When analyzed as a continuous variable, a 2% risk reduction (95% CI 0-3%) was estimated for every 100 μg/day increase in total folate intake.

Conclusion: These data support the hypothesis that higher folate intake is modestly associated with reduced risk of colon cancer.

Fig. 1

Study-specific and pooled multivariate relative risks and 95% confidence intervals of colon cancer for comparison of the highest vs lowest quintile of dietary (a) and total (b) folate intake. The black squares and horizontal lines correspond to the study-specific relative risks and 95% confidence intervals for the comparison of quintile 5 to quintile 1 of folate consumption. The relative risks were adjusted for the same covariates listed in Table 2. The area of the black squares reflects the study-specific weight (inverse of the variance). The diamond represents the pooled relative risk and 95% confidence interval. Study abbreviations are the following: ATBC Alpha-Tocopherol Beta-Carotene Cancer Prevention Study, BCDDP Breast Cancer Detection Demonstration Project Follow-Up Cohort, CNBSS Canadian National Breast Screening Study, CPS2_f Cancer Prevention Study II Nutrition Cohort, women, CPS2_m Cancer Prevention Study II Nutrition Cohort, men, HPFS Health Professionals Follow-up Study, IWHS Iowa Women’s Health Study, NLCS_f Netherlands Cohort Study, women, NLCS_m Netherlands Cohort Study, men, NYS_f New York State Cohort, women, NYS_m New York State Cohort, men, NYUWHS New York University Women’s Health Study, NHSa Nurses’ Health Study (a), and NHSb Nurses’ Health Study (b), ORDET Prospective Study on Hormones, Diet and Breast Cancer, SMC Swedish Mammography Cohort, WHS Women’s Health Study