TABLE 3.
HRs of invasive breast cancer associated with cumulative average dietary and supplemental vitamin C intake in the NHS (1980–2014; n = 88,041) and NHSII (1991–2013; n = 93,372)1
| Dietary vitamin C intake | Supplemental vitamin C intake | |||||||
|---|---|---|---|---|---|---|---|---|
| Median, mg/d | No. of cases/person-years | HR (95% CI)2 | HR (95% CI)3 | Median, mg/d | No. of cases/person-years | HR (95% CI)2 | HR (95% CI)3 | |
| NHS | ||||||||
| Quintile 1 | 76 | 1505/478,025 | 1 (ref) | 1 (ref) | 23 | 1118/325,936 | 1 (ref) | 1 (ref) |
| Quintile 2 | 110 | 1600/501,631 | 1.00 (0.93–1.07) | 0.96 (0.90–1.04) | 60 | 1060/323,735 | 0.97 (0.89–1.05) | 0.97 (0.89–1.06) |
| Quintile 3 | 137 | 1617/502,616 | 0.99 (0.92–1.06) | 0.94 (0.88–1.01) | 139 | 1139/325,885 | 1.01 (0.93–1.09) | 0.98 (0.90–1.07) |
| Quintile 4 | 167 | 1689/501,743 | 1.02 (0.95–1.10) | 0.98 (0.91–1.05) | 298 | 1194/324,466 | 1.06 (0.97–1.15) | 1.03 (0.95–1.12) |
| Quintile 5 | 218 | 1536/468,192 | 1.00 (0.93–1.07) | 0.97 (0.90–1.04) | 652 | 1033/300,888 | 0.99 (0.91–1.07) | 0.97 (0.89–1.05) |
| — | — | — | P trend = 0.83 | P trend = 0.62 | — | — | P trend = 0.73 | P trend = 0.74 |
| NHSII | ||||||||
| Quintile 1 | 63 | 641/384,334 | 1 (ref) | 1 (ref) | 21 | 439/268,518 | 1 (ref) | 1 (ref) |
| Quintile 2 | 92 | 708/396,290 | 1.07 (0.96–1.19) | 1.04 (0.94–1.16) | 46 | 441/256,218 | 1.09 (0.96–1.25) | 1.11 (0.97–1.27) |
| Quintile 3 | 117 | 641/394,030 | 0.96 (0.86–1.07) | 0.93 (0.83–1.04) | 98 | 461/260,297 | 1.11 (0.97–1.26) | 1.11 (0.97–1.26) |
| Quintile 4 | 147 | 668/393,090 | 1.00 (0.89–1.11) | 0.96 (0.86–1.07) | 231 | 472/261,119 | 1.06 (0.93–1.21) | 1.05 (0.92–1.19) |
| Quintile 5 | 200 | 653/376,131 | 1.03 (0.92–1.15) | 1.00 (0.89–1.12) | 558 | 501/247,581 | 1.14 (1.01–1.30) | 1.13 (0.99–1.29) |
| — | — | — | P trend = 0.88 | P trend = 0.76 | — | — | P trend = 0.12 | P trend = 0.22 |
| Pooled | ||||||||
| Quintile 1 | 76 | 2146/862,359 | 1 (ref) | 1 (ref) | 21 | 1557/594,455 | 1 (ref) | 1 (ref) |
| Quintile 2 | 110 | 2308/897,921 | 1.02 (0.96–1.08) | 0.99 (0.93–1.05) | 51 | 1501/579,953 | 1.00 (0.93–1.08) | 1.01 (0.94–1.09) |
| Quintile 3 | 137 | 2258/896,645 | 0.98 (0.92–1.04) | 0.94 (0.88–1.00) | 118 | 1600/586,182 | 1.04 (0.97–1.11) | 1.02 (0.95–1.09) |
| Quintile 4 | 167 | 2357/894,833 | 1.02 (0.96–1.08) | 0.97 (0.92–1.03) | 265 | 1666/585,584 | 1.06 (0.99–1.13) | 1.04 (0.97–1.11) |
| Quintile 5 | 218 | 2189/844,322 | 1.01 (0.95–1.07) | 0.98 (0.92–1.04) | 601 | 1534/548,469 | 1.03 (0.96–1.11) | 1.02 (0.94–1.09) |
| — | — | — | P trend = 0.80 | P trend = 0.57 | — | — | P trend = 0.29 | P trend = 0.77 |
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.
Unadjusted. Stratified by age and period.
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), 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), and mutually adjusted for dietary vitamin C intake (quintiles and missing category; time-dependent) or use of supplements containing vitamin C (never, current, past, missing; time-dependent). Stratified by age and period and additionally stratified by cohort in pooled analyses.