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.

Breast Cancer After Treatment of Differentiated Thyroid Cancer With Radioiodine in Young Females: What We Know and How to Investigate Open Questions. Review of the Literature and Results of a Multi-Registry Survey

“…In any case, levothyroxine therapy, aiming at thyroid-stimulating hormone suppression in patients with advanced DTC, is suspected to increase breast cancer risk independent of DTC ( 55 ). In addition, endocrine disruptors like nitrate may play a role in the pathogenesis of DTC and breast cancer ( 56 , 57 ).…”

Cytological Characteristics of Postoperative Metastases of Papillary Thyroid Cancer During the Development of Secondary Radioiodine Refractoriness

“…As a result of the Chernobyl accident, there was a sharp increase in incidence of the thyroid cancer [1,2]. For 20 years of observation, most cases of differentiated thyroid cancer (DTC) have shown the excellent prognosis for more than 95 % of patients thanks to thyroidectomy and radioiodine (RI) -therapy, based on the unique ability of the thyroid cells to accumulate RI [3,4].…”

Morphological features of radioiodine-resistance metastases of thyroid papillary carcinoma

“…The highest increase in the level of thyroid cancer was observed among subjects whose age at the time of the accident was 18 years and younger. So, four years after the Chernobyl disaster, the incidence of thyroid cancer in children increased by 4.8 times, and in subsequent years exceeded the accident rate by 10 times [3,9,23]. However, in contrast to carcinoma of other localizations, differentiated thyroid cancer in most cases has a favorable prognosis: the survival 5-year rate of patients with thyroid cancer is about 98%, and 20-30 years of survival exceeds 90% [10,14,15].…”