Table 4.
Associations between nitrite and nitrate exposures by sources and prostate cancer risk, NutriNet-Santé cohort, France, 2009–2021 (N = 21 772 men)
| Exposure | Sex-specific categories of intakesa |
P trend | |||
|---|---|---|---|---|---|
| 1 | 2 | 3 | |||
| Total nitrites | N cases/N total | 95/7258 | 169/7257 | 136/7257 | |
| HR (95% CI) | Ref. | 1.27 (0.97–1.65) | 1.28 (0.95–1.73) | 0.2 | |
| Nitrites from natural sources | N cases/N total | 94/7258 | 167/7257 | 139/7257 | |
| HR (95% CI) | Ref. | 1.19 (0.91–1.55) | 1.25 (0.92–1.68) | 0.2 | |
| Nitrites from food additives | N cases/N total | 56/5443 | 182/8165 | 162/8164 | |
| HR (95% CI) | Ref. | 1.30 (0.95–1.77) | 1.58 (1.14–2.18) | 0.008 | |
| Sodium nitrite (e250) | N cases/N total | 56/5456 | 181/8159 | 163/8157 | |
| HR (95% CI) | Ref. | 1.31 (0.96–1.79) | 1.62 (1.17–2.25) | 0.004 | |
| Total nitrates | N cases/N total | 74/7258 | 146/7258 | 180/7256 | |
| HR (95% CI) | Ref. | 1.16 (0.87–1.55) | 1.18 (0.87–1.60) | 0.4 | |
| Nitrates from natural sources | N cases/N total | 74/7258 | 146/7258 | 180/7256 | |
| HR (95% CI) | Ref. | 1.16 (0.87–1.55) | 1.16 (0.86–1.58) | 0.4 | |
| Nitrates from food additives | N cases/N total | 198/13 622 | 133/4075 | 69/4075 | |
| HR (95% CI) | Ref. | 1.38 (1.10–1.74) | 0.99 (0.74–1.33) | 0.9 | |
| Potassium nitrate (e252) | N cases/N total | 198/13 623 | 133/4074 | 69/4075 | |
| HR (95% CI) | Ref. | 1.39 (1.10–1.75) | 1.03 (0.77–1.38) | 0.9 | |
HR, cause-specific hazard ratio.
Median follow-up time: 6.8 years. Person-years: 139 334.
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 nitrites and nitrates from overall exposure and from natural sources, sex-specific tertiles of consumption were defined.
Cut-offs were: 5.18 and 7.44 mg/d in men for overall nitrites, 162.11 and 251.59 mg/d in men for overall nitrates, 4.92 and 7.07 mg/d in men for nitrites from natural sources and 161.94 and 251.32 mg/d in men 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: 0.25 mg/d in men for nitrites from food additives, 0.46 mg/d in men for nitrates from food additives, 0.25 mg/d in men for sodium nitrite (e250) and 0.46 mg/d in men for potassium nitrate (e252).
During men's follow-up, 84 competing deaths occurred and 649 competing cases of cancers other than prostate. 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 and potassium nitrate (e252) were respectively: 0.58 (0.32–1.06), P = 0.1; 0.45 (0.24–0.85), P = 0.02; 1.37 (0.73–2.54), P = 0.4; 1.31 (0.70–2.43), P = 0.4; 1.04 (0.53–2.04), P = 0.7; 1.15 (0.59–2.28), P = 0.9; 1.01 (0.55–1.86), P = 1; 1.00 (0.54–1.84), P = 1. Cause-specific hazard ratios for all cancers except prostate 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: 0.86 (0.69–1.08), P = 0.2; 0.88 (0.70–1.10), P = 0.3; 0.96 (0.76–1.22), P = 0.7; 0.96 (0.76–1.22), P = 0.7; 1.15 (0.91–1.45), P = 0.3; 1.13 (0.90–1.43), P = 0.4; 1.05 (0.85–1.30), P = 0.6; 1.05 (0.85–1.30), P = 0.6.