Thyroid Cancer Induction: Nitrates as Independent Risk Factors or Risk Modulators after Radiation Exposure, with a Focus on the Chernobyl Accident

Abstract

In recent decades, differentiated thyroid cancer (DTC) incidence has been increasing worldwide. The important contributions to this phenomenon of "overdiagnosis" driven by wider use of improved ultrasound systems are amply documented, notwithstanding the "real" carcinogenic effects of ionizing radiation, e.g., from the Chernobyl accident or health care interventions. Less well understood is the role of nitrates - as environmental pollutants, in diet, and in medication - in thyroid carcinogenesis. Increasing exposure to nitrates is associated with rising incidence of esophageal, stomach, bladder, and colon cancers. Recent data suggest that in agricultural areas with higher mean nitrate levels in groundwater, DTC risk is also elevated. Our work in Belarus after Chernobyl has shown that children in districts with high nitrate concentrations in drinking water had significantly higher thyroid cancer incidence after irradiation than did their counterparts in areas with lower nitrate concentrations. Notwithstanding thyroid shielding, increasing use of computed tomography and dental X-rays heightens radiation exposure of the salivary glands in the general population, especially in children and adolescents. When nitrate intake is increased, salivary gland irradiation may potentially result in carcinogenic elevations in plasma nitric oxide concentrations. In conclusion, excess nitrate intake seems to be an independent risk factor for DTC. Additionally, we hypothesize from our data that high nitrate levels modulate the carcinogenic effect of radiation on the thyroid. Cohort studies, case-control studies, or both, are needed to quantify the effects of nitrates on DTC risk in the presence or absence of radiation exposure, e.g., that associated with diagnostic or therapeutic health care interventions.

Keywords: Belarus; Chernobyl; Ionizing radiation; Nitrate pollution; Risk stratification; Salivary glands; Thyroid cancer.

Fig. 1

Maps of Belarus depicting by district (oblast) the level of groundwater pollution with nitrate (mg/L) measured in open wells in 1988–1990 (a) and the prevalence (per 1,000) of pediatric thyroid cancer in 1986–2005 in the cohort ages 0–18 years at exposure to radioactive fallout from the Chernobyl accident (b). In b, areas exposed to such fallout are bounded with black lines, and radioactive contamination due to radioiodine in 1986 (in kBq/m²) is shown in small numerals. Notably, areas of greatest pediatric thyroid cancer prevalence tend to coincide with areas characterized by both a high radiation exposure and high nitrate pollution of groundwater.