TABLE 4.
HRs of invasive breast cancer associated with the use of dietary supplements containing vitamin C in the NHS (1980–2014; n = 88,041) and NHSII (1991–2013; n = 93,372)1
| Pooled | No. of cases/person-years | HR (95% CI)2 | HR (95% CI)3 | HR (95% CI)4 |
|---|---|---|---|---|
| Ever supplemental vitamin C intake ≥750 mg/day | ||||
| Never use | 3103/1,412,452 | 1 (ref) | 1 (ref) | 1 (ref) |
| Ever use ≥750 mg/d | 2888/976,073 | 1.06 (1.00–1.11) | 0.96 (0.90–1.01) | 0.96 (0.90–1.01) |
| Ever use <750 mg/d | 5267/2,007,555 | 1.04 (0.99–1.09) | 0.97 (0.93–1.02) | 0.97 (0.92–1.02) |
| Duration of use of single vitamin C supplements | ||||
| Never use of any supplement with vitamin C | 3103/1,412,452 | 1 (ref) | 1 (ref) | 1 (ref) |
| Current use, <5 years | 628/270,176 | 1.05 (0.96–1.14) | 0.96 (0.88–1.04) | 0.95 (0.87–1.04) |
| Current use, 5–9 years | 602/224,035 | 1.05 (0.96–1.14) | 0.94 (0.86–1.03) | 0.94 (0.86–1.03) |
| Current use, ≥10 years | 1329/395,256 | 1.11 (1.04–1.19) | 0.97 (0.91–1.04) | 0.97 (0.91–1.04) |
| Past use, <5 years | 1098/364,227 | 1.12 (1.04–1.20) | 1.00 (0.93–1.07) | 0.99 (0.92–1.07) |
| Past use, 5–9 years | 525/170,352 | 1.08 (0.98–1.18) | 0.95 (0.87–1.05) | 0.95 (0.86–1.05) |
| Past use, ≥10 years | 517/161,107 | 1.06 (0.96–1.17) | 0.93 (0.84–1.02) | 0.93 (0.84–1.02) |
| Ever use of multivitamins containing vitamin C | 2912/1,217,158 | 0.99 (0.94–1.04) | 0.97 (0.92–1.02) | 0.97 (0.92–1.02) |
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), 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), and total duration of lactation (<12, ≥12 months). Stratified by age and period and additionally stratified by cohort in pooled analyses.
Additionally adjusted for AHEI score without alcohol (quintiles and missing category; time-dependent) and dietary vitamin C intake.