Table 3.
Associations between nitrite and nitrate exposures by sources and breast cancer risk, NutriNet-Santé cohort, France, 2009–2021 (N = 79 284 women)
| Exposure | Sex-specific categories of intakesa |
P trend | |||
|---|---|---|---|---|---|
| 1 | 2 | 3 | |||
| Total nitrites | N cases/N total | 222/26 428 | 382/26 428 | 362/26 428 | |
| HR (95% CI) | Ref. | 1.19 (1.00–1.41) | 1.09 (0.90–1.32) | 0.7 | |
| Nitrites from natural sources | N cases/N total | 226/26 428 | 369/26 428 | 371/26 428 | |
| HR (95% CI) | Ref. | 1.09 (0.92–1.30) | 1.04 (0.86–1.26) | 0.9 | |
| Nitrites from food additives | N cases/N total | 175/20 894 | 441/29 195 | 350/29 195 | |
| HR (95% CI) | Ref. | 1.22 (1.01–1.47) | 1.15 (0.94–1.39) | 0.8 | |
| Sodium nitrite (e250) | N cases/N total | 175/20 941 | 440/29 172 | 351/29 171 | |
| HR (95% CI) | Ref. | 1.22 (1.02–1.47) | 1.16 (0.95–1.41) | 0.6 | |
| Total nitrates | N cases/N total | 219/26 428 | 355/26 428 | 392/26 428 | |
| HR (95% CI) | Ref. | 0.99 (0.83–1.18) | 0.99 (0.81–1.20) | 1 | |
| Nitrates from natural sources | N cases/N total | 220/26 428 | 354/26 428 | 392/26 428 | |
| HR (95% CI) | Ref. | 0.98 (0.82–1.17) | 1.00 (0.82–1.21) | 1 | |
| Nitrates from food additives | N cases/N total | 575/55 461 | 224/11 912 | 167/11 911 | |
| HR (95% CI) | Ref | 1.20 (1.02–1.41) | 1.24 (1.03–1.48) | 0.02 | |
| Potassium nitrate (e252) | N cases/N total | 575/55 463 | 224/11 911 | 167/11 910 | |
| HR (95% CI) | Ref. | 1.20 (1.02–1.41) | 1.25 (1.04–1.50) | 0.01 | |
HR, cause-specific hazard ratio.
Median follow-up time: 6.7 years. Person-years: 500 421.
Multivariable Cox proportional hazard models were adjusted for: age (timescale), energy intake without alcohol (kcal/d, continuous), alcohol, sugar, saturated fatty acids and fibre intakes (g/d, continuous), sodium and heme iron intakes (mg/d, continuous), body mass index (kg/m2, continuous), height (cm, continuous), physical activity (high, moderate, low, calculated according to International Physical Activity Questionnaire recommendations), smoking status (never, former, current smokers), number of 24-h dietary records (continuous), family history of cancer (yes/no) and educational level (primary, secondary, undergraduate, post-graduate). All models were mutually adjusted for nitrate/nitrite intakes other than the specific one studied.
For breast cancer analyses, additional adjustments were made for the age at menarche (categorical: <12 years old, ≥12 years old), age at first child (categorical: no child, before 30 years, ≥30 years), number of biological children (continuous), menopausal status at baseline (menopausal/non-menopausal), hormonal treatment for menopause at baseline and during follow-up (yes/no) and oral contraception use at baseline and during follow-up (yes/no).
For nitrites and nitrates from overall exposure and from natural sources, sex-specific tertiles of consumption were defined.
Cut-offs were: 4.03 and 5.55 mg/d in women for overall nitrites, 150.09 and 233.89 mg/d in women for overall nitrates, 3.83 and 5.29 mg/d in women for nitrites from natural sources and 149.91 and 233.75 mg/d in women for nitrates from natural sources.
For nitrites and nitrates from food additives, three categories of consumption were defined: non-consumers, low consumers and high consumers (separated by sex-specific median among consumers). Cut-offs were: 0.19 mg/d in women for nitrites from food additives, 0.36 mg/d in women for nitrates from food additives, 0.19 mg/d in women for sodium nitrite (e250) and 0.36 mg/d in women for potassium nitrate (e252).
During women's follow-up, 58 competing deaths occurred and 1296 competing cases of cancers other than breast were diagnosed. Cause-specific HRs for death in the high consumers of total nitrites, nitrites from natural sources, nitrites from food additives, sodium nitrite (e250), total nitrates, nitrates from natural sources, nitrates from food additives, potassium nitrate (e252) were respectively: 0.87 (0.43–1.74), P = 0.8; 0.96 (0.46–1.99), P = 0.9; 0.93 (0.47–1.85), P = 0.9; 0.95 (0.48–1.89), P = 0.9; 0.94 (0.44–2.00), P = 0.8; 0.93 (0.44–1.99), P = 0.8; 0.83 (0.36–1.90), P = 0.6; 0.88 (0.38–2.01), P = 0.7.
Cause-specific hazard ratios for all cancers except breast in the high consumers of total nitrites, nitrites from natural sources, nitrites from food additives, sodium nitrite (e250), total nitrates, nitrates from natural sources, nitrates from food additives and potassium nitrate (e252) were respectively: 1.06 (0.90–1.24), P = 0.5; 1.00 (0.85–1.18), P = 1; 0.98 (0.84–1.15), P = 0.8; 1.00 (0.85–1.18), P = 1; 0.96 (0.81–1.14), P = 0.6; 0.96 (0.81–1.13), P = 0.6; 1.03 (0.88–1.21), P = 0.7; 1.05 (0.89–1.23), P = 0.6.