TABLE 2.
Risk of colorectal cancer according to folate intake in the Nurses' Health Study (NHS) and the Health Professionals Follow-Up Study (HPFS)1
| Baseline | Simple update (0–4-y lag) | 4–8-y lag | 8–12-y lag | 12–16-y lag | Cumulative average | ||
| No. of cases (NHS, HPFS) | 1069, 987 | 1120, 813 | 1010, 684 | 829, 477 | 645, 277 | 1312, 987 | |
| Total folate2 | |||||||
| <250 μg/d | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | |
| 250 to <400 μg/d | 0.91 (0.76, 1.08) | 0.96 (0.82, 1.12) | 0.94 (0.70, 1.27) | 0.91 (0.78, 1.06) | 0.83 (0.70, 0.99) | 0.95 (0.81, 1.12) | |
| 400 to <600 μg/d | 0.86 (0.69, 1.06) | 1.00 (0.84, 1.19) | 0.83 (0.70, 0.99) | 0.88 (0.73, 1.06) | 0.82 (0.50, 1.36) | 0.90 (0.78, 1.04) | |
| 600 to <800 μg/d | 0.84 (0.69, 1.03) | 0.92 (0.77, 1.10) | 0.85 (0.71, 1.02) | 0.91 (0.75, 1.11) | 0.73 (0.57, 0.94) | 0.84 (0.70, 1.00) | |
| ≥800 μg/d | 0.74 (0.60, 0.92) | 0.88 (0.72, 1.07) | 0.92 (0.75, 1.13) | 0.88 (0.68, 1.13) | 0.69 (0.51, 0.94) | 0.85 (0.68, 1.08) | |
| P for trend3 | 0.02 | 0.19 | 0.67 | 0.45 | 0.04 | 0.07 | |
| P for heterogeneity4 | 0.91 | 0.57 | 0.98 | 0.94 | 0.36 | 0.50 | |
| Dietary folate25 | |||||||
| <250 μg/d | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | |
| 250 to <300 μg/d | 1.02 (0.90, 1.16) | 0.95 (0.82, 1.12) | 0.97 (0.82, 1.16) | 1.08 (0.93, 1.27) | 0.91 (0.76, 1.09) | 1.07 (0.94, 1.22) | |
| 300 to <400 μg/d | 1.04 (0.90, 1.19) | 0.99 (0.81, 1.21) | 0.96 (0.83, 1.10) | 0.88 (0.66, 1.18) | 0.84 (0.70, 1.01) | 1.02 (0.89, 1.15) | |
| 400 to <500 μg/d | 0.89 (0.74, 1.08) | 1.13 (0.85, 1.50) | 0.92 (0.76, 1.11) | 0.95 (0.67, 1.33) | 0.92 (0.68, 1.24) | 1.00 (0.83, 1.21) | |
| ≥500 μg/d | 0.86 (0.67, 1.10) | 1.03 (0.81, 1.31) | 0.91 (0.72, 1.16) | 0.82 (0.58, 1.18) | 0.60 (0.39, 0.91) | 1.07 (0.82, 1.38) | |
| P for trend3 | 0.32 | 0.51 | 0.49 | 0.43 | 0.01 | 0.92 | |
| P for heterogeneity4 | 0.91 | 0.26 | 0.98 | 0.23 | 0.83 | 0.99 | |
| Natural folate25 | |||||||
| <200 μg/d | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | |
| 200 to <250 μg/d | 0.93 (0.81, 1.07) | 1.24 (0.94, 1.63) | 1.00 (0.84, 1.19) | 0.99 (0.84, 1.18) | 0.93 (0.77, 1.12) | 1.09 (0.79, 1.51) | |
| 250 to <300 μg/d | 0.96 (0.83, 1.11) | 1.10 (0.92, 1.31) | 0.92 (0.78, 1.08) | 0.96 (0.80, 1.15) | 0.91 (0.74, 1.13) | 1.00 (0.86, 1.16) | |
| 300 to <400 μg/d | 1.02 (0.87, 1.20) | 1.18 (1.00, 1.40) | 0.92 (0.78, 1.09) | 0.98 (0.81, 1.19) | 0.89 (0.71, 1.11) | 1.08 (0.92, 1.27) | |
| ≥400 μg/d | 0.94 (0.74, 1.18) | 1.23 (0.81, 1.89) | 1.05 (0.83, 1.32) | 0.96 (0.72, 1.27) | 0.85 (0.60, 1.19) | 1.13 (0.87, 1.46) | |
| P for trend3 | 0.83 | 0.16 | 0.92 | 0.53 | 0.08 | 0.66 | |
| P for heterogeneity4 | 0.98 | 0.08 | 0.33 | 0.34 | 0.47 | 0.52 | |
| Synthetic folic acid2 | |||||||
| <50 μg/d | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | 1.00 | |
| 50 to <100 μg/d | 0.87 (0.70, 1.09) | 1.03 (0.88, 1.19) | 1.04 (0.89, 1.21) | 0.81 (0.60, 1.10) | 0.77 (0.57, 1.05) | 0.89 (0.77, 1.02) | |
| 100 to <200 μg/d | 0.81 (0.70, 0.95) | 0.94 (0.81, 1.10) | 0.89 (0.75, 1.05) | 0.83 (0.68, 1.02) | 0.92 (0.73, 1.17) | 0.97 (0.86, 1.10) | |
| 200 to <400 μg/d | 0.91 (0.79, 1.04) | 0.93 (0.80, 1.08) | 0.90 (0.77, 1.05) | 0.92 (0.77, 1.10) | 0.81 (0.52, 1.27) | 0.89 (0.78, 1.00) | |
| ≥400 μg/d | 0.85 (0.75, 0.98) | 0.91 (0.77, 1.07) | 0.96 (0.76, 1.21) | 0.91 (0.77, 1.08) | 0.78 (0.64, 0.97) | 0.93 (0.81, 1.06) | |
| P for trend3 | 0.03 | 0.11 | 0.66 | 0.40 | 0.06 | 0.26 | |
| P for heterogeneity4 | 0.36 | 0.22 | 0.11 | 0.39 | 0.36 | 0.75 | |
All values are pooled multivariate relative risks; 95% CIs in parentheses. Total folate was from foods and supplements. Follow-up years were 1980–2004 in the NHS and 1986–2004 in the HPFS for the 0–4-y lag, 1984–2004 in the NHS and 1990–2004 in the HPFS for the 4–8-y lag, 1988–2004 in the NHS and 1994–2004 in the HPFS for the 8–12-y lag, and 1992–2004 in the NHS and 1998–2004 in the HPFS for the 12–16-y lag. Natural folate was derived from foods alone. Synthetic folic acid was derived from supplements and folic acid–fortified foods.
A Cox proportional hazards model was used and adjusted for age, calendar year, pack-years of smoking before age 30 y (never smoker, 1–4 pack-years, 5–10 pack-years, or ≥11 pack-years of smoking), physical activity (quintiles of metabolic equivalent tasks/wk), aspirin dose (never, past, or current use of 1–2, 3–5, 6–14, or ≥15 tablets/wk), height (continuous), BMI (in kg/m2; <23, 23 to <25, 25 to <30, 30 to <35, or ≥35), family history of colorectal cancer in parents and siblings (yes or no), menopausal status and hormone therapy use (only in women; premenopausal women and never use, past use, or current use in postmenopausal women), history of endoscopy (yes or no), red meat intake (quintiles), alcohol intake (never and 0.1–9.9, 10–14.9, 15–29.9, or ≥30 g alcohol/d), calcium intake from foods (continuous), and total energy intake (continuous).
Two-sided; calculated by using Wald's test statistic.
Two-sided; calculated by using the Q test statistic.
Additionally adjusted for multivitamin use (never; past; current: 1–5, 6–9, 10–15, 16–19, or ≥20 y).