TABLE 5.
HRs of invasive breast cancer associated with dietary and supplemental vitamin C intake in the NHS (1980–2014; n = 88,041) and NHSII (1991–2013; n = 93,372)1
| Total vitamin C intake | Dietary vitamin C intake | Supplemental vitamin C intake | ||||
|---|---|---|---|---|---|---|
| No. of cases | HR (95% CI)2 | No. of cases | HR (95% CI)3 | No. of cases | HR (95% CI)4 | |
| Lag 0–4 years | ||||||
| Quintile 1 | 1956 | 1 (ref) | 2005 | 1 (ref) | 926 | 1 (ref) |
| Quintile 2 | 2062 | 1.01 (0.95–1.07) | 1984 | 0.95 (0.89–1.01) | 129 | 0.97 (0.89–1.05) |
| Quintile 3 | 1976 | 0.94 (0.89–1.01) | 2068 | 0.97 (0.91–1.04) | 1024 | 0.95 (0.86–1.03) |
| Quintile 4 | 2010 | 0.97 (0.91–1.03) | 2090 | 0.97 (0.91–1.03) | 1211 | 1.00 (0.92–1.09) |
| Quintile 5 | 2118 | 0.99 (0.93–1.05) | 1975 | 0.94 (0.89–1.01) | 1192 | 0.99 (0.91–1.08) |
| — | — | P trend = 0.89 | — | P trend = 0.24 | — | P trend = 0.39 |
| Lag 4–8 years | ||||||
| Quintile 1 | 1706 | 1 (ref) | 1715 | 1 (ref) | 656 | 1 (ref) |
| Quintile 2 | 1706 | 0.94 (0.88–1.01) | 1743 | 0.96 (0.90–1.03) | 1100 | 1.06 (0.96–1.17) |
| Quintile 3 | 1796 | 0.97 (0.91–1.04) | 1745 | 0.95 (0.89–1.01) | 795 | 0.99 (0.89–1.10) |
| Quintile 4 | 1726 | 0.95 (0.89–1.02) | 1808 | 0.97 (0.90–1.04) | 905 | 1.03 (0.93–1.14) |
| Quintile 5 | 1842 | 0.97 (0.91–1.04) | 1765 | 0.98 (0.91–1.05) | 888 | 1.02 (0.92–1.13) |
| — | — | P trend = 0.98 | — | P trend = 0.71 | — | P trend = 0.73 |
| Lag 8–12 years | ||||||
| Quintile 1 | 1515 | 1 (ref) | 1546 | 1 (ref) | 605 | 1 (ref) |
| Quintile 2 | 1598 | 0.99 (0.93–1.07) | 1547 | 0.94 (0.88–1.01) | 875 | 0.99 (0.89–1.10) |
| Quintile 3 | 1592 | 0.98 (0.91–1.05) | 1648 | 0.99 (0.92–1.06) | 773 | 1.06 (0.95–1.17) |
| Quintile 4 | 1617 | 1.01 (0.94–1.08) | 1595 | 0.95 (0.88–1.02) | 761 | 0.96 (0.87–1.07) |
| Quintile 5 | 1625 | 0.98 (0.91–1.06) | 1611 | 0.99 (0.92–1.07) | 796 | 1.06 (0.95–1.17) |
| — | — | P trend = 0.60 | — | P trend = 0.91 | — | P trend = 0.55 |
| Lag 12–16 years | ||||||
| Quintile 1 | 1272 | 1 (ref) | 1262 | 1 (ref) | 477 | 1 (ref) |
| Quintile 2 | 1241 | 0.93 (0.79–1.09) | 1286 | 0.97 (0.83–1.14) | 689 | 0.93 (0.74–1.16) |
| Quintile 3 | 1306 | 0.95 (0.81–1.12) | 1296 | 1.01 (0.86–1.19) | 530 | 0.81 (0.63–1.02) |
| Quintile 4 | 1250 | 0.94 (0.80–1.11) | 1304 | 0.97 (0.82–1.14) | 614 | 1.00 (0.80–1.25) |
| Quintile 5 | 1288 | 0.94 (0.79–1.10) | 1209 | 0.83 (0.70–0.99) | 567 | 0.86 (0.69–1.09) |
| — | — | P trend = 0.96 | — | P trend = 0.05 | — | P trend = 0.85 |
| Lag 16–20 years | ||||||
| Quintile 1 | 964 | 1 (ref) | 973 | 1 (ref) | 333 | 1 (ref) |
| Quintile 2 | 989 | 0.97 (0.89–1.06) | 967 | 0.93 (0.85–1.02) | 469 | 0.94 (0.81–1.08) |
| Quintile 3 | 1015 | 1.00 (0.91–1.09) | 1000 | 0.97 (0.89–1.07) | 418 | 1.00 (0.86–1.15) |
| Quintile 4 | 956 | 0.97 (0.88–1.06) | 1008 | 0.96 (0.88–1.05) | 354 | 0.83 (0.71–0.96) |
| Quintile 5 | 946 | 0.94 (0.85–1.03) | 922 | 0.92 (0.84–1.01) | 397 | 0.93 (0.80–1.07) |
| — | — | P trend = 0.11 | — | P trend = 0.19 | — | P trend = 0.49 |
| Lag 20–24 years5 | ||||||
| Quintile 1 | 549 | 1 (ref) | 573 | 1 (ref) | 158 | 1 (ref) |
| Quintile 2 | 582 | 1.02 (0.91–1.15) | 548 | 0.90 (0.80–1.01) | 271 | 1.11 (0.91–1.35) |
| Quintile 3 | 590 | 1.04 (0.92–1.17) | 571 | 0.95 (0.85–1.07) | 181 | 0.93 (0.75–1.16) |
| Quintile 4 | 543 | 0.99 (0.87–1.11) | 595 | 0.98 (0.88–1.11) | 206 | 1.03 (0.84–1.27) |
| Quintile 5 | 542 | 1.00 (0.88–1.12) | 519 | 0.90 (0.79–1.01) | 236 | 1.23 (1.01–1.51) |
| — | — | P trend = 0.69 | — | P trend = 0.30 | — | P trend = 0.20 |
| Lag 24–28 years5 | ||||||
| Quintile 1 | 387 | 1 (ref) | 359 | 1 (ref) | 126 | 1 (ref) |
| Quintile 2 | 385 | 0.97 (0.84–1.11) | 369 | 0.97 (0.83–1.12) | 179 | 1.01 (0.81–1.28) |
| Quintile 3 | 409 | 1.04 (0.90–1.20) | 377 | 1.03 (0.89–1.19) | 136 | 0.96 (0.75–1.22) |
| Quintile 4 | 353 | 0.93 (0.80–1.08) | 398 | 1.07 (0.92–1.23) | 128 | 0.87 (0.68–1.11) |
| Quintile 5 | 329 | 0.90 (0.77–1.04) | 360 | 1.03 (0.88–1.19) | 145 | 1.06 (0.83–1.34) |
| — | — | P trend = 0.11 | — | P trend = 0.49 | — | P trend = 0.93 |
Vitamin C intake was adjusted for total energy intake using the residual method. Numbers do not add up to total numbers of cases and person-years because of missing values. Abbreviations: AHEI, alternate healthy eating index; NHS, Nurses’ Health Study; NHSII, Nurses’ Health Study II.
Adjusted for menopausal status and age at menopause (premenopausal; postmenopausal and <45 years at menopause; postmenopausal and 45–49 years at menopause; postmenopausal and 50–52 years at menopause; postmenopausal and ≥53 years at menopause; missing; time-dependent), age at menarche (<12, 12 to <13, 13 to <14, 14 to <15, ≥15 years), parity and age at first birth (nulliparous; 1 child and <25 years at first birth; 1 child and ≥25 years at first birth; ≥2 children and <25 years at first birth; ≥2 children and ≥25 years at first birth; missing; time-dependent), use of oral contraceptive (ever, never; time-dependent), personal history of biopsy-confirmed benign breast disease (yes, no; time-dependent), family history of breast cancer (yes, no; time-dependent), total energy intake without alcohol (quintiles; time-dependent), cumulative average alcohol intake (nonusers and quartiles of intakes; time-dependent), BMI at age 18 (<19, 19 to <21, 21 to <23, 23 to <27, ≥27 kg/m2, missing), weight change since age 18 by menopausal status (lost ≥2 kg and premenopausal; lost <2 kg or gained ≤2 kg and premenopausal; gained >2 to 5 kg and premenopausal; gained >5 to 10 kg and premenopausal; gained >10 to 20 kg and premenopausal; gained >20 to 25 kg and premenopausal; gained ≥25 kg and premenopausal; lost ≥2 kg and postmenopausal; lost <2 kg or gained ≤2 kg and postmenopausal; gained >2 to 5 kg and postmenopausal; gained >5 to 10 kg and postmenopausal; gained >10 to 20 kg and postmenopausal; gained >20 to 25 kg and postmenopausal; gained ≥25 kg and postmenopausal; missing; time-dependent), physical activity (quintiles and missing category; time-dependent), recent mammography (yes, no, missing; time-dependent), postmenopausal hormone use (never, past, current, missing; time-dependent), duration of use of postmenopausal hormone therapy with estrogen alone (continuous in months; time-dependent), duration of use of estrogen and progestin postmenopausal hormone therapy (continuous in months), height (<1.60, 1.60 to <1.65, 1.65 to <1.70, 1.70 to <1.75, ≥1.75 meters), total duration of lactation (<12, ≥12 months), AHEI score without alcohol (quintiles and missing category; time-dependent). Stratified by age and period and additionally stratified by cohort in pooled analyses.
Additionally adjusted for the use of supplements containing vitamin C (never, current, past, missing; time-dependent).
Additionally adjusted for dietary vitamin C intake (quintiles and missing category; time-dependent).
Analyses conducted in NHS data only (1980–2012, n = 88,041).