Table 2.
Associations between nitrite and nitrate exposures by sources and overall cancer risk, NutriNet-Santé cohort, France, 2009–2021 (N = 101 056)
| Exposure | Sex-specific categories of intakesa |
P trend | |||
|---|---|---|---|---|---|
| 1 | 2 | 3 | |||
| Total nitrites | N cases/N total | 831/33 686 | 1262/33 685 | 1218/33 685 | |
| HR (95% CI) | Ref. | 1.04 (0.95–1.14) | 1.01 (0.91–1.11) | 0.9 | |
| Nitrites from natural sources | N cases/N total | 828/33 686 | 1243/33 685 | 1240/33 685 | |
| HR (95% CI) | Ref. | 1.00 (0.91–1.09) | 0.97 (0.88–1.08) | 0.5 | |
| Nitrites from food additives | N cases/N total | 639/26 337 | 1467/37 360 | 1205/37 359 | |
| HR (95% CI) | Ref. | 1.08 (0.98–1.19) | 1.08 (0.98–1.20) | 0.3 | |
| Sodium nitrite (e250) | N cases/N total | 639/26 397 | 1463/37 331 | 1209/37 328 | |
| HR (95% CI) | Ref. | 1.08 (0.98–1.19) | 1.10 (0.99–1.21) | 0.2 | |
| Total nitrates | N cases/N total | 740/33 686 | 1195/33 686 | 1376/33 684 | |
| HR (95% CI) | Ref. | 1.02 (0.93–1.12) | 1.02 (0.92–1.13) | 0.8 | |
| Nitrates from natural sources | N cases/N total | 741/33 686 | 1196/33 686 | 1374/33 684 | |
| HR (95% CI) | Ref. | 1.02 (0.93–1.12) | 1.02 (0.92–1.13) | 0.8 | |
| Nitrates from food additives | N cases/N total | 1974/69 083 | 760/15 987 | 577/15 986 | |
| HR (95% CI) | Ref. | 1.08 (0.99–1.18) | 1.09 (0.99–1.20) | 0.09 | |
| Potassium nitrate (e252) | N cases/N total | 1975/69 086 | 760/15 985 | 576/15 985 | |
| HR (95% CI) | Ref. | 1.08 (0.99–1.18) | 1.09 (0.99–1.21) | 0.07 | |
HR, cause-specific hazard ratio.
Median follow-up time: 6.7 years. Person-years: 639 756.
Multivariable Cox proportional hazard models were adjusted for: age (timescale), sex, 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 total nitrite and nitrate intakes and from natural sources, sex-specific tertiles of consumption were defined. Cut-offs were: 4.03 and 5.55 mg/d in women and 5.18 and 7.44 mg/d in men for total nitrites, 150.09 and 233.89 mg/d in women and 162.11 and 251.59 mg/d in men for total nitrates, 3.83 and 5.29 mg/d in women and 4.92 and 7.07 mg/d in men for nitrites from natural sources, 149.91 and 233.75 mg/d in women 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: 0.19 mg/d in women and 0.25 mg/d in men for nitrites from food additives, 0.36 mg/d in women and 0.46 mg/d in men for nitrates from food additives, 0.19 mg/d in women and 0.25 mg/d in men for sodium nitrite (e250) and 0.36 mg/d in women and 0.46 mg/d in men for potassium nitrate (e252).
During overall follow-up, 142 competing deaths occurred. 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: 0.65 (0.41–1.02), P = 0.09; 0.58 (0.37–0.93), P = 0.03; 1.17 (0.74–1.85), P = 0.5; 1.15 (0.73–1.82), P = 0.6; 0.99 (0.60–1.63), P = 0.6; 1.05 (0.63–1.73), P = 0.8; 0.93 (0.57–1.52), P = 0.004; 0.94 (0.58- 1.53), P = 0.8.