TABLE 1.
Quartile of intake2 |
|||||
1 | 2 | 3 | 4 | P for trend3 | |
Current folate intake | |||||
Dietary, natural and synthetic from foods | |||||
Median intake (μg/d) | 210 (37 to <260) | 303 (260 to <346) | 392 (346 to <450) | 541 (450–1483) | |
Cases | 165 | 161 | 180 | 157 | |
Multi-RR (95% CI) | 1.00 | 0.94 (0.75, 1.18) | 1.04 (0.82, 1.33) | 0.91 (0.68, 1.22) | 0.76 |
Supplemental | |||||
Median intake category (μg/d) | None | 86 (86 to <200) | 314 (200 to <400) | 400 (400–1400) | |
Cases | 251 | 13 | 90 | 384 | |
Multi-RR (95% CI) | 0.98 (0.55, 1.75) | 0.87 (0.67, 1.13) | 1.00 (0.84, 1.19) | 0.95 | |
Total4 | |||||
Median intake category (DFE/d) | 325 (45 to <472) | 604 (472 to <776) | 960 (776 to <1082) | 1302 (1082–3663) | |
Cases | 153 | 91 | 193 | 222 | |
Multi-RR (95% CI) | 1.00 | 0.92 (0.70, 1.20) | 1.02 (0.82, 1.27) | 0.90 (0.72, 1.12) | 0.52 |
10-y Average folate intake | |||||
Supplemental | |||||
Median intake (μg/d) | None | 80 (9 to <200) | 251 (200 to <400) | 400 (400–1400) | |
Cases | 202 | 167 | 135 | 234 | |
Multi-RR (95% CI) | 1.00 | 1.00 (0.81, 1.22) | 0.87 (0.70, 1.08) | 0.87 (0.72, 1.06) | 0.10 |
Total45 | |||||
Median intake (DFE/d) | 345 (45 to <472) | 609 (472 to <776) | 942 (776 to <1082) | 1272 (1082–3620) | |
Cases | 169 | 164 | 177 | 149 | |
Multi-RR (95% CI) | 1.00 | 0.96 (0.77, 1.20) | 0.95 (0.77, 1.18) | 0.78 (0.61, 0.99) | 0.05 |
Methionine intake | |||||
Dietary | |||||
Median intake (g/d) | 0.82 (0.12 to <1.03) | 1.22 (1.03 to <1.40) | 1.59 (1.40 to <1.82) | 2.17 (1.82–6.41) | |
Cases | 171 | 179 | 160 | 153 | |
Multi-RR (95% CI) | 1.00 | 0.98 (0.78, 1.22) | 0.84 (0.65, 1.08) | 0.78 (0.56, 1.09) | 0.09 |
Riboflavin | |||||
Dietary | |||||
Median intake (mg/d) | 1.10 (0.21 to <1.36) | 1.60 (1.36 to <1.83) | 2.09 (1.83 to <2.42) | 2.93 (2.42–9.52) | |
Cases | 161 | 164 | 188 | 150 | |
Multi-RR (95% CI) | 1.00 | 0.97 (0.78, 1.22) | 1.07 (0.84, 1.36) | 0.86 (0.64, 1.15) | 0.54 |
10-y Average supplemental | |||||
Median intake (mg/d) | None | 0.34 (0.07 to <0.67) | 1.07 (0.67–1.36) | 1.70 (1.70–1.70) | |
Cases | 226 | 160 | 142 | 215 | |
Multi-RR (95% CI) | 1.00 | 1.02 (0.83, 1.25) | 0.83 (0.67, 1.03) | 0.87 (0.72, 1.06) | 0.07 |
Total5 | |||||
Median intake (mg/d) | 1.46 (0.29 to <1.90) | 2.32 (1.90 to <2.70) | 3.07 (2.70 to <3.47) | 4.04 (3.47–10.0) | |
Cases | 165 | 165 | 173 | 160 | |
Multi-RR (95% CI) | 1.00 | 0.96 (0.77, 1.20) | 0.95 (0.76, 1.18) | 0.83 (0.65, 1.07) | 0.17 |
Vitamin B-6 intake | |||||
Dietary | |||||
Median intake (mg/d) | 0.96 (0.20 to <1.18) | 1.39 (1.18 to <1.58) | 1.79 (1.58 to <2.05) | 2.45 (2.05–7.26) | |
Cases | 159 | 172 | 181 | 151 | |
Multi-RR (95% CI) | 1.00 | 1.04 (0.83, 1.30) | 1.08 (0.84, 1.38) | 0.90 (0.66, 1.21) | 0.61 |
10-y Average supplemental | |||||
Median intake (mg/d) | None | 0.50 (0.09 to <1.26) | 2.00 (1.26 to <2.89) | 10.7 (2.89–261) | |
Cases | 204 | 159 | 194 | 184 | |
Multi-RR (95% CI) | 1.00 | 0.88 (0.72, 1.09) | 0.90 (0.73, 1.09) | 0.90 (0.73, 1.10) | 0.31 |
Total5 | |||||
Median intake (mg/d) | 1.34 (0.29 to <1.83) | 2.37 (1.83 to <3.05) | 3.75 (3.05 to <4.84) | 12.6 (4.84–263) | |
Cases | 162 | 168 | 164 | 169 | |
Multi-RR (95% CI) | 1.00 | 1.00 (0.80, 1.25) | 0.90 (0.71, 1.13) | 0.99 (0.79, 1.24) | 0.69 |
Vitamin B-12 intake | |||||
Dietary | |||||
Median intake (μg/d) | 2.71 (0.02 to <3.60) | 4.42 (3.60 to <5.23) | 6.14 (5.23 to <7.35) | 9.33 (7.35–62.9) | |
Cases | 169 | 178 | 151 | 165 | |
Multi-RR (95% CI) | 1.00 | 0.99 (0.80, 1.23) | 0.84 (0.66, 1.06) | 0.91 (0.70, 1.18) | 0.28 |
10-y Average supplemental | |||||
Median intake (μg/d) | None | 2.40 (0.13–4.80) | 6.25 (4.84 to <12.5) | 25.0 (12.5–300) | |
Cases | 197 | 144 | 199 | 193 | |
Multi-RR (95% CI) | 1.00 | 0.84 (0.68, 1.04) | 0.97 (0.80, 1.18) | 0.96 (0.78, 1.17) | 0.97 |
Total5 | |||||
Median intake (μg/d) | 4.26 (0.23 to 6.31) | 8.46 (6.31 to <10.8) | 14.1 (10.8 to <19.6) | 32 (19.6–310) | |
Cases | 163 | 162 | 159 | 179 | |
Multi-RR (95% CI) | 1.00 | 0.95 (0.76, 1.19) | 0.89 (0.71, 1.12) | 0.99 (0.79, 1.23) | 0.83 |
Multivitamin use | |||||
By category (d/wk of use) | None | 0.30 to <2.80 (tertile 1) | 2.80 to <7.00 (tertile 2) | 7.00 (tertile 3) | |
Cases | 226 | 160 | 142 | 215 | |
Multi-RR (95% CI) | 1.00 | 1.02 (0.83, 1.25) | 0.83 (0.67, 1.03) | 0.87 (0.72, 1.06) | 0.07 |
Total alcohol intake | |||||
By category (g/d) | <1.5 (category 1) | 1.5–4.9 (category 2) | 5.0–9.9 (category 3) | ≥10 (category 4) | |
Cases | 379 | 100 | 80 | 171 | |
Multi-RR (95% CI) | 1.00 | 1.01 (0.80, 1.29) | 1.22 (0.95, 1.57) | 1.60 (1.31, 1.94) | <0.0001 |
Age- and multivariable-adjusted RRs (multi-RRs) were similar; thus only multi-RRs are reported. Multi-RRs and associated 95% CIs were estimated by using a Cox regression model adjusted for age (y), race (white or other), family history of breast cancer (none, 1 affected mother or sister, or ≥2 affected mother or sisters), mammography within 2 y preceding baseline (no or yes), history of breast biopsy (no or yes), age at menarche (≤11, 12, 13, or ≥14 y), age at first birth (nulliparous, or ≤19, 20–24, 25–34, or ≥35 y), age at menopause (≤44, 45–49, or ≥50 y), years of combined estrogen and progestin postmenopausal hormone use (never or <1, 1–4, 5–9, or ≥10), BMI (in kg/m2; <25, 25 to <30, or ≥30), height (<62, 62 to <65, 65 to <68, or ≥68 in.; 1 in. = 2.54 cm), total physical activity (none, 1–3 tertiles of metabolic equivalent hours/wk), and alcohol intake in the past year (<1.5, 1.5–4.9, 5.0–9.9, or ≥10 g/d). We additionally adjusted for total energy intake (kcal/d) in analyses of dietary and total nutrient intakes. Case numbers do not sum to the total number of cases because of missing data. For median intakes, ranges are in parentheses.
Exposure data reported by quartiles, except for multivitamin use (reported as none or by tertile categories) and alcohol consumption (reported based on a priori–defined categories as indicated). Current supplemental and current total folate categories were based on cutoffs of 10-y folate intakes to facilitate comparison.
Calculated by modeling categories of the exposure as a single ordinal variable in a Cox regression; a Wald test was used to obtain a P value.
Total folate reported in dietary folate equivalents (DFE) = synthetic folate (μg) × 1.7 + food folate (μg). Dietary and synthetic folate do not add up to total folate because a conversion factor was used to take into account the higher bioavailability of synthetic folate.
Total intake was calculated as the sum of dietary intakes over the year before baseline plus the 10-y average from supplements.