Table 3.
Hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer (BC) by daily dietary intake of methyl-group donors (MGDs) by levels of alcohol intake in 318,686 women in the EPIC cohort.
| Low Alcohol Intake (<2 Drinks/Week) (N = 157,363) |
Moderate Alcohol Intake (2–12 Drinks/Week) (N = 124,578) |
High Alcohol Intake (>12 Drinks/Week) (N = 36,745) |
||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| BC Cases | Person Years | Multivariable Model a
HR (95% CI) |
BC Cases | Person Years | Multivariable Model a
HR (95% CI) |
BC Cases | Person Years | Multivariable Model a
HR (95% CI) |
Pinteraction b, c | |
| MGD score | ||||||||||
| Continuous (1 unit) | 5882 | 2,241,059 | 0.99 (0.97–1.01) | 5448 | 1,748,126 | 1.00 (0.98–1.02) | 1990 | 503,575 | 1.00 (0.97–1.03) | 0.049 b |
| Q1: ≤ −2.58 | 1324 | 504,409 | 1 (Ref.) | 963 | 307,475 | 1 (Ref.) | 281 | 73,439 | 1 (Ref.) | |
| Q2: > −2.58–−1.00 | 1175 | 459,463 | 0.92 (0.85–1.01) | 1039 | 349,334 | 0.95 (0.86–1.04) | 375 | 89,680 | 1.12 (0.95–1.32) | |
| Q3: > −1.00–0.39 | 1154 | 450,289 | 0.91 (0.82–1.00) | 1134 | 362,348 | 1.00 (0.91–1.11) | 412 | 93,145 | 1.20 (1.01–1.44) | |
| Q4: > 0.39–2.31 | 1127 | 433,205 | 0.90 (0.81–1.01) | 1151 | 369,993 | 1.00 (0.89–1.12) | 390 | 106,439 | 1.02 (0.83–1.24) | |
| Q5: > 2.31 | 1102 | 393,694 | 0.90 (0.78–1.04) | 1161 | 358,976 | 1.02 (0.87–1.19) | 532 | 140,871 | 1.10 (0.86–1.41) | 0.025 c |
| Ptrend | 0.210 | 0.586 | 0.867 | |||||||
| Dietary folate (µg/day) | ||||||||||
| Continuous (per 1 SD = 128 µg/day) | 5882 | 2,241,059 | 0.96 (0.91–1.02) | 5448 | 1,748,126 | 1.03 (0.97–1.09) | 1990 | 503,575 | 1.10 (1.00–1.20) | 0.063 b |
| Q1: ≤ 242 | 1438 | 533,297 | 1 (Ref.) | 975 | 298,193 | 1 (Ref.) | 311 | 71,589 | 1 (Ref.) | |
| Q2: > 242–298 | 1211 | 458,111 | 0.93 (0.86–1.02) | 1076 | 350,013 | 0.98 (0.89–1.08) | 397 | 93,099 | 1.02 (0.87–1.19) | |
| Q3: > 298–357 | 1067 | 431,110 | 0.85 (0.77–0.94) | 1113 | 366,994 | 1.02 (0.92–1.13) | 389 | 101,785 | 0.95 (0.80–1.13) | |
| Q4: > 357–440 | 1101 | 417,655 | 0.89 (0.79–0.99) | 1152 | 368,818 | 1.09 (0.97–1.23) | 430 | 109,863 | 1.00 (0.82–1.22) | |
| Q5: > 440 | 1065 | 400,886 | 0.85 (0.74–0.98) | 1132 | 364,109 | 1.12 (0.96–1.31) | 463 | 127,239 | 1.00 (0.78–1.29) | 0.231 c |
| Ptrend | 0.052 | 0.059 | 0.998 | |||||||
| Dietary choline (mg/day) | ||||||||||
| Continuous (per 1 SD = 90 mg/day) | 5882 | 2,241,059 | 0.99 (0.95–1.02) | 5448 | 174,8126 | 1.01 (0.97–1.05) | 1990 | 503,575 | 1.01 (0.95–1.07) | 0.064 b |
| Q1: ≤ 202 | 1365 | 535,685 | 1 (Ref.) | 858 | 284,036 | 1 (Ref.) | 225 | 61,666 | 1 (Ref.) | |
| Q2: < 202–244 | 1226 | 471,093 | 0.97 (0.90–1.06) | 1055 | 337,077 | 1.03 (0.94–1.13) | 345 | 85,676 | 1.12 (0.94–1.33) | |
| Q3: < 244–285 | 1136 | 444,750 | 0.94 (0.86–1.03) | 1038 | 359,764 | 0.94 (0.85–1.03) | 380 | 99,898 | 1.06 (0.89–1.27) | |
| Q4: < 285–339 | 1106 | 418,570 | 0.94 (0.85–1.04) | 1171 | 378,671 | 0.98 (0.88–1.09) | 439 | 112,623 | 1.09 (0.91–1.31) | |
| Q5: > 339 | 1049 | 370,961 | 0.92 (0.82–1.04) | 1326 | 388,578 | 1.04 (0.92–1.17) | 601 | 143,712 | 1.13 (0.93–1.38) | 0.292 c |
| Ptrend | 0.177 | 0.577 | 0.344 | |||||||
| Dietary betaine (mg/day) | ||||||||||
| Continuous (per 1 SD = 88 mg /day) | 5882 | 2,241,059 | 1.01 (0.97–1.04) | 5448 | 1,748,126 | 0.96 (0.92–1.00) | 1990 | 503,575 | 1.02 (0.95–1.08) | 0.037 b |
| Q1: ≤ 39 | 1089 | 378,757 | 1 (Ref.) | 1254 | 359,896 | 1 (Ref.) | 440 | 102,142 | 1 (Ref.) | |
| Q2: < 39–88 | 1160 | 464,885 | 0.93 (0.85–1.03) | 1240 | 373,502 | 0.96 (0.87–1.05) | 416 | 98,141 | 1.06 (0.91–1.24) | |
| Q3: < 88–132 | 1264 | 474,910 | 1.01 (0.91–1.13) | 1031 | 342,637 | 0.92 (0.83–1.03) | 364 | 88,983 | 1.19 (0.99–1.44) | |
| Q4: < 132–193 | 1194 | 447,685 | 1.03 (0.92–1.15) | 1040 | 353,835 | 0.94 (0.83–1.05) | 408 | 107,715 | 1.13 (0.93–1.38) | |
| Q5: > 193 | 1175 | 474,821 | 0.98 (0.87–1.10) | 883 | 318,255 | 0.89 (0.79–1.02) | 362 | 106,593 | 1.12 (0.90–1.39) | 0.221 c |
| Ptrend | 0.741 | 0.126 | 0.497 | |||||||
| Dietary methionine (g/day) | ||||||||||
| Continuous (per 1 g/day) | 5882 | 2,241,059 | 0.95 (0.88–1.02) | 5448 | 1,748,126 | 1.02 (0.94–1.10) | 1990 | 503,575 | 0.88 (0.77–1.00) | 0.018 b |
| Q1: ≤ 1.06 | 1175 | 510,519 | 1 (Ref.) | 826 | 321,954 | 1 (Ref.) | 281 | 78,502 | 1 (Ref.) | |
| Q2: < 1.06–1.30 | 1230 | 469,493 | 1.05 (0.96–1.14) | 1033 | 339,137 | 1.01 (0.92–1.11) | 328 | 87,739 | 0.94 (0.80–1.11) | |
| Q3: < 1.30–1.54 | 1220 | 451,112 | 1.03 (0.95–1.13) | 1093 | 353,461 | 0.99 (0.89–1.09) | 418 | 94,445 | 1.09 (0.92–1.28) | |
| Q4: < 1.54–1.85 | 1140 | 423,892 | 0.99 (0.90–1.09) | 1226 | 367,949 | 1.02 (0.9–1.14) | 449 | 106,363 | 1.02 (0.86–1.22) | |
| Q5: > 1.85 | 1117 | 386,043 | 0.98 (0.87–1.10) | 1270 | 365,624 | 1.03 (0.91–1.16) | 514 | 136,526 | 0.87 (0.71–1.07) | 0.023 c |
| Ptrend | 0.460 | 0.581 | 0.200 | |||||||
a Multivariable model: Cox regression model stratified by study center and by one year categories of age at recruitment and adjusted for total energy intake (kcal/day), dietary fiber intake (g/day), height (cm), BMI (kg/m2), highest level of education (primary/no schooling, technical/professional/secondary, longer education, unknown), physical activity (inactive, moderately inactive, moderately active, active, unknown), smoking status (never, former, current smoker, unknown), ever use of vitamin/mineral supplements (yes, no, unknown), menopausal status at recruitment (premenopausal, postmenopausal (including surgical postmenopausal), perimenopausal), age at menarche (≤12, 13, 14, ≥15), ever use of hormones for menopause (no, yes, unknown), ever use of contraceptive pill (no, yes, unknown), and age at first full term pregnancy (nulliparous, ≤21 year, 22–29 year, ≥30 year). b Pinteraction between MGDs and alcohol intake when considering the MGDs as continuous variables and alcohol intake as a categorical variable (low, moderate and high alcohol consumers). c Pinteraction between MGDs and alcohol intake when considering the MGDs as categorical variables (quintiles) and alcohol intake as a categorical variable (low, moderate and high alcohol consumers). Abbreviations: HR: hazard ratio; CI: confidence interval; BC: breast cancer; Q: quintile; MGD: methyl-group donor; Ref: reference; N: number of participants; SD: standard deviation.