Ingested nitrate and nitrite, drinking water disinfection by-products, and incidence of thyroid cancer among licensed pesticide applicators and spouses in the Agricultural Health Study

BACKGROUND: Ingested nitrate and nitrite and some disinfection by-products (DBPs) are suspected carcinogens. However, epidemiologic evidence linking these exposures to thyroid cancer (TC) is limited. OBJECTIVES: We examined water nitrate and dietary nitrate and nitrite exposures in relation to incident TC in the Agricultural Health Study. We stratified analyses by sex and smoking status. We also explored associations with two drinking water DBPs, total trihalomethanes (TTHM) and five haloacetic acids (HAA5). METHODS: We determined the primary drinking water source for participants at enrollment (1993-1997). We computed nitrate and DBP exposures for public water supply users (N = 14,779) from historical measurement data. For private well users (N = 44,896), we estimated nitrate exposure using random forest models and assumed they had negligible DBP exposures. Dietary nitrate and nitrite exposures were assessed among 29,371 participants who completed a diet history questionnaire at the first follow-up (1999-2003). We calculated adjusted hazard ratios (HRs) and 95 %CI for associations of tertiles (T) of exposure with incident TCs between study enrollment or first follow-up and 2021. RESULTS: We found modest but statistically non-significant associations between water nitrate exposure and TC in women (T2 vs. T1 HR: 1.37, 95 %CI: 0.86, 2.21; T3 vs. T1 HR: 1.44, 95 %CI: 0.91, 2.26) and ever smokers (T3 vs. T1 HR: 1.72, 95 %CI: 0.91, 3.27) without evidence of a trend (p-trend>0.05). No association was found for dietary nitrate, dietary nitrite, or drinking water DBPs. CONCLUSION: We did not find clear evidence associating drinking water nitrate, drinking water DBPs, or dietary nitrate and nitrite with TC.