TABLE 4.
Multivariate HRs and 95% CIs for the associations of one-carbon metabolism nutrient intake with colorectal cancer by time since exposure to folic acid fortification1
| Fortification (total patient-years) |
|||||||||||||
| <3 y (5123)2 |
3 to <6 y (21,434) |
6 to <9 y (163,885) |
≥9 y (693,016) |
||||||||||
| Cases | HR | (95% CI) | Cases | HR | (95% CI) | Cases | HR | (95% CI) | Cases | HR | (95% CI) | P-interaction3 | |
| Dietary folate | <0.01 | ||||||||||||
| <189 DFE | 55 | 1.00 | (Ref) | 83 | 1.00 | (Ref) | 48 | 1.00 | (Ref) | 35 | 1.00 | (Ref) | |
| 189 to <252 DFE | 52 | 0.16 | (0.79, 1.70) | 67 | 0.96 | (0.69, 1.33) | 42 | 0.98 | (0.64, 1.48) | 33 | 0.91 | (0.56, 1.47) | |
| 252 to <343 DFE | 33 | 0.77 | (0.49, 1.20) | 71 | 1.17 | (0.85, 1.61) | 70 | 1.74 | (1.20, 2.52) | 42 | 1.18 | (0.75, 1.86) | |
| ≥343 DFE | 15 | 0.85 | (0.48, 1.52) | 58 | 1.54 | (1.09, 2.16) | 71 | 3.24 | (2.23, 4.72) | 33 | 1.36 | (0.84, 2.22) | |
| P-trend | 0.31 | <0.01 | <0.01 | 0.12 | |||||||||
| Supplemental folic acid | 0.57 | ||||||||||||
| 0 μg | 83 | 1.00 | (Ref) | 156 | 1.00 | (Ref) | 115 | 1.00 | (Ref) | 71 | 1.00 | (Ref) | |
| >0–400 μg | 67 | 1.04 | (0.75, 1.45) | 113 | 1.05 | (0.82, 1.34) | 101 | 1.15 | (0.88, 1.51) | 60 | 0.97 | (0.69, 1.37) | |
| >400 μg | 5 | 0.69 | (0.28, 1.73) | 10 | 0.85 | (0.45, 1.63) | 15 | 1.55 | (0.90, 2.66) | 12 | 1.72 | (0.93, 3.19) | |
| P-trend | 0.80 | 0.98 | 0.11 | 0.36 | |||||||||
| Folate, total | 0.09 | ||||||||||||
| <242 DFE | 57 | 1.00 | (Ref) | 82 | 1.00 | (Ref) | 47 | 1.00 | (Ref) | 32 | 1.00 | (Ref) | |
| 242 to <542 DFE | 27 | 0.68 | (0.43, 1.10) | 73 | 1.25 | (0.91, 1.72) | 62 | 1.69 | (1.16, 2.48) | 37 | 1.26 | (0.78, 2.02) | |
| 542 to <939 DFE | 49 | 1.09 | (0.73, 1.61) | 64 | 1.06 | (0.76, 1.48) | 53 | 1.44 | (0.97, 2.14) | 38 | 1.25 | (0.78, 2.01) | |
| ≥939 DFE | 22 | 0.70 | (0.42, 1.16) | 60 | 1.42 | (1.01, 1.99) | 69 | 2.48 | (1.69, 3.62) | 36 | 1.36 | (0.84, 2.21) | |
| P-trend | 0.87 | 0.23 | <0.01 | 0.30 | |||||||||
| Dietary vitamin B-12 | 0.18 | ||||||||||||
| <3.52 μg | 47 | 1.00 | (Ref) | 74 | 1.00 | (Ref) | 57 | 1.00 | (Ref) | 38 | 1.00 | (Ref) | |
| 3.52–5.14 μg | 37 | 0.86 | (0.56, 1.34) | 75 | 1.22 | (0.88, 1.69) | 53 | 1.02 | (0.70, 1.48) | 27 | 0.70 | (0.43, 1.14) | |
| 5.15–7.27 μg | 39 | 0.81 | (0.52, 1.24) | 64 | 1.01 | (0.72, 1.42) | 53 | 0.98 | (0.67, 1.43) | 38 | 0.95 | (0.61, 1.50) | |
| >7.27 μg | 32 | 0.73 | (0.47, 1.16) | 66 | 0.86 | (0.62, 1.21) | 68 | 1.23 | (0.86, 1.76) | 40 | 1.03 | (0.66, 1.62) | |
| P-trend | 0.18 | 0.20 | 0.23 | 0.54 | |||||||||
| Supplemental vitamin B-12 | 0.14 | ||||||||||||
| 0 mg | 79 | 1.00 | (Ref) | 151 | 1.00 | (Ref) | 115 | 1.00 | (Ref) | 70 | 1.00 | (Ref) | |
| >0–6.0 mg | 65 | 1.21 | (0.86, 1.69) | 96 | 1.03 | (0.80, 1.34) | 82 | 1.07 | (0.80, 1.43) | 56 | 1.05 | (0.73, 1.49) | |
| >6.0 mg | 11 | 0.55 | (0.29, 1.04) | 32 | 1.00 | (0.68, 1.48) | 34 | 1.26 | (0.86, 1.86) | 17 | 0.91 | (0.54, 1.56) | |
| P-trend | 0.06 | 0.99 | 0.28 | 0.75 | |||||||||
| Vitamin B-12 intake, total | 0.11 | ||||||||||||
| <5.13 μg | 44 | 1.00 | (Ref) | 79 | 1.00 | (Ref) | 49 | 1.00 | (Ref) | 31 | 1.00 | (Ref) | |
| 5.13–8.98 μg | 42 | 0.97 | (0.63, 1.49) | 70 | 0.95 | (0.68, 1.31) | 65 | 1.35 | (0.93, 1.96) | 40 | 1.25 | (0.78, 1.99) | |
| 8.99–12.87 μg | 44 | 1.02 | (0.67, 1.56) | 74 | 1.18 | (0.86, 1.63) | 55 | 1.27 | (0.86, 1.87) | 37 | 1.17 | (0.73, 1.90) | |
| >12.87 μg | 25 | 0.65 | (0.39, 1.07) | 56 | 0.82 | (0.58, 1.16) | 62 | 1.43 | (0.98, 2.09) | 35 | 1.14 | (0.70, 1.86) | |
| P-trend | 0.10 | 0.36 | 0.11 | 0.76 | |||||||||
| Dietary vitamin B-6 | 0.07 | ||||||||||||
| <1.16 mg | 49 | 1.00 | (Ref) | 92 | 1.00 | (Ref) | 50 | 1.00 | (Ref) | 34 | 1.00 | (Ref) | |
| 1.16–1.53 mg | 44 | 1.05 | (0.70, 1.59) | 61 | 0.74 | (0.53, 1.02) | 63 | 1.32 | (0.91, 1.92) | 35 | 1.00 | (0.62, 1.61) | |
| 1.54–1.99 mg | 37 | 0.86 | (0.56, 1.34) | 70 | 0.89 | (0.65, 1.22) | 52 | 1.07 | (0.72, 1.58) | 38 | 1.05 | (0.66, 1.68) | |
| >1.99 mg | 25 | 0.65 | (0.40, 1.06) | 56 | 0.69 | (0.49, 0.97) | 66 | 1.36 | (0.94, 1.97) | 36 | 1.01 | (0.63, 1.62) | |
| P-trend | 0.06 | 0.07 | 0.21 | 0.95 | |||||||||
| Supplemental vitamin B-6 | 0.09 | ||||||||||||
| 0 mg | 81 | 1.00 | (Ref) | 152 | 1.00 | (Ref) | 115 | 1.00 | (Ref) | 70 | 1.00 | (Ref) | |
| >0–2.0 mg | 65 | 1.20 | (0.86, 1.68) | 92 | 0.99 | (0.76, 1.28) | 83 | 1.07 | (0.81, 1.43) | 53 | 1.00 | (0.69, 1.43) | |
| >2.0 mg | 9 | 0.47 | (0.24, 0.95) | 35 | 1.07 | (0.73, 1.55) | 33 | 1.24 | (0.84, 1.83) | 20 | 1.05 | (0.64, 1.73) | |
| P-trend | 0.03 | 0.73 | 0.33 | 0.84 | |||||||||
| Vitamin B-6 intake, total | 0.27 | ||||||||||||
| <1.52 mg | 48 | 1.00 | (Ref) | 78 | 1.00 | (Ref) | 58 | 1.00 | (Ref) | 34 | 1.00 | (Ref) | |
| 1.52–2.74 mg | 36 | 0.93 | (0.60, 1.45) | 76 | 1.07 | (0.78, 1.47) | 61 | 1.04 | (0.72, 1.49) | 32 | 0.91 | (0.56, 1.48) | |
| 2.75–3.88 mg | 51 | 1.24 | (0.83, 1.87) | 68 | 1.10 | (0.79, 1.53) | 54 | 1.03 | (0.71, 1.50) | 42 | 1.21 | (0.76, 1.91) | |
| >3.88 mg | 20 | 0.56 | (0.33, 0.95) | 57 | 0.97 | (0.69, 1.38) | 58 | 1.15 | (0.79, 1.66) | 35 | 1.04 | (0.64, 1.68) | |
| P-trend | 0.07 | 0.83 | 0.47 | 0.68 | |||||||||
| Dietary riboflavin | 0.11 | ||||||||||||
| <1.37 mg | 51 | 1.00 | (Ref) | 74 | 1.00 | (Ref) | 48 | 1.00 | (Ref) | 27 | 1.00 | (Ref) | |
| 1.37–1.84 mg | 35 | 0.77 | (0.50, 1.20) | 67 | 1.05 | (0.75, 1.46) | 60 | 1.30 | (0.89, 1.90) | 43 | 1.46 | (0.90, 2.37) | |
| 1.85–2.43 mg | 40 | 0.76 | (0.50, 1.16) | 71 | 1.18 | (0.85, 1.65) | 63 | 1.33 | (0.91, 1.94) | 29 | 0.95 | (0.56, 1.61) | |
| >2.43 mg | 29 | 0.59 | (0.37, 0.94) | 67 | 1.03 | (0.74, 1.45) | 60 | 1.20 | (0.81, 1.76) | 44 | 1.43 | (0.88, 2.32) | |
| P-trend | 0.03 | 0.78 | 0.49 | 0.35 | |||||||||
| Supplemental riboflavin | 0.20 | ||||||||||||
| 0 mg | 82 | 1.00 | (Ref) | 156 | 1.00 | (Ref) | 117 | 1.00 | (Ref) | 71 | 1.00 | (Ref) | |
| >0–1.7 mg | 64 | 1.14 | (0.81, 1.59) | 96 | 1.00 | (0.77, 1.29) | 85 | 1.07 | (0.80, 1.42) | 56 | 1.03 | (0.72, 1.47) | |
| >1.7 mg | 9 | 0.49 | (0.25, 0.99) | 27 | 0.96 | (0.63, 1.45) | 29 | 1.18 | (0.78, 1.77) | 16 | 0.94 | (0.54, 1.62) | |
| P-trend | 0.046 | 0.84 | 0.43 | 0.80 | |||||||||
| Riboflavin intake, total | 0.07 | ||||||||||||
| <1.80 mg | 49 | 1.00 | (Ref) | 78 | 1.00 | (Ref) | 52 | 1.00 | (Ref) | 30 | 1.00 | (Ref) | |
| 1.80–2.87 mg | 37 | 0.83 | (0.54, 1.27) | 77 | 1.14 | (0.83, 1.57) | 58 | 1.09 | (0.75, 1.58) | 40 | 1.23 | (0.77, 1.98) | |
| 2.88–3.97 mg | 48 | 1.09 | (0.72, 1.64) | 65 | 1.06 | (0.76, 1.48) | 62 | 1.28 | (0.88, 1.85) | 41 | 1.28 | (0.79, 2.05) | |
| >3.97 mg | 21 | 0.48 | (0.28, 0.81) | 59 | 1.00 | (0.71, 1.42) | 59 | 1.21 | (0.83, 1.77) | 32 | 0.99 | (0.60, 1.64) | |
| P-trend | 0.01 | 0.87 | 0.29 | 0.78 | |||||||||
1
Colorectal cancer risks for dietary, supplemental, and total intake of each nutrient were estimated in separate models. A Cox model adjusted for age, BMI (in kg/m2; <25, 25 to <30, 30 to <35, or ≥35), race-ethnicity (white, black, or other), past medical history of colonoscopy (yes or no), smoking status (never, past, or current), physical activity (0 to 3, 3 to <11.75, or ≥11.75 metabolic equivalent task hours/wk), and postmenopausal hormone use (never, past, or current). DFE, dietary folate equivalent; Ref, reference.
2
For the majority of women who were exposed to <3 y of folic acid fortification, dietary folate intake likely consisted of natural folate only.
3
P value for test of interaction between the linear trend variable of interest and fortification year categories.