Exposure to nitrosatable drugs during pregnancy and childhood cancer: A cohort study in Taiwan

Nitrosatable drugs can contribute to the endogenous formation of N-nitroso compounds (NOCs) in humans. NOCs are carcinogenic in animal systems. However, the relationship between nitrosatable drug exposure in pregnancy and childhood cancer risk remains inconclusive. Using the Taiwan Maternal and Child Health Database (N = 2,090,806), we conducted a population-based cohort study of mother-child pairs with children born 2004-2015, to investigate the link between exposure to nitrosatable drugs in pregnancy and childhood cancer risk among offspring. Prescriptions of nitrosatable drugs were obtained from the National Health Insurance Program, and cancer cases were ascertained through linkage to the Cancer Registry. Cox proportional hazards regression models were applied to estimate both crude and adjusted hazard ratios (aHR) with 95% confidence intervals (CI). Among 3203 cancer cases, nitrosatable drug exposure was associated with higher risks of neuroblastoma (aHR = 1.27, 95% CI: 0.95-1.73) and hepatoblastoma (aHR = 1.49, 95% CI: 0.97-2.28). Neuroblastoma (aHR = 1.32, 95% CI: 0.96-1.82) and osteosarcoma (aHR = 2.05, 95% CI: 1.07-3.89) were most strongly associated with amides, while the risk of hepatoblastoma was highest among offspring of tertiary amine users (aHR = 1.57, 95% CI: 1.00-2.46), compared to other functional groups. Some results may need to be interpreted with caution due to the wide confidence intervals. Our findings highlight the need for future research into the biological mechanisms between NOCs and childhood cancer.