Cancer
Exposure to nitrosatable drugs in pregnancy and pediatric cancer risk: a population-based cohort study in Taiwan Chuanjie Deng* Chuanjie Deng Ya-Hui Hu Pei-Chen Lee Anupong Sirirungreung Eugenia Yupei Chock Zeyan Liew Beate Ritz Julia E. Heck
Background: Nitrosatable drugs, including secondary and tertiary amines and amides, have been implicated in the endogenous formation of N-nitroso compounds (NOCs) in the human stomach, with experimental evidence linking NOCs to carcinogenicity in animals. However, the association between maternal nitrosatable drug use and pediatric cancer risk remains inconclusive.
Methods: We conducted a population-based retrospective cohort study based on the Taiwan Maternal and Child Health Database (N=2,199,302) from 2004-2015 to investigate the potential association between maternal nitrosatable drug use in pregnancy and pediatric cancer risk among offspring. Nitrosatable drug prescriptions were identified from the National Health Insurance Program using Anatomical Therapeutic Chemical (ATC) codes, and cancer cases were ascertained through linkage to the Cancer Registry (1979-2017). Cox proportional hazards regression was employed with adjustment for parental age and socioeconomic status.
Results: In 2,659 cancer cases we identified, maternal nitrosatable drug use in pregnancy was associated with an elevated risk of overall cancer (HR=1.25, 95% CI: 1.04-1.50) and astrocytoma (HR=3.21, CI: 1.02-10.07) in offspring. Secondary amines exhibited a positive association with hepatoblastoma (HR=1.65, CI: 1.12-2.44), while children of mothers who took tertiary amines had a higher risk of overall cancer (HR=1.11, CI: 1.03-1.21), hepatoblastoma (HR=1.99, CI: 1.32-2.98) and germ cell tumors (HR=1.33, CI: 1.02-1.74), particularly among males (HR=1.50, CI: 1.04-2.16). Amides were strongly associated with medulloblastoma (HR=2.16, CI: 1.08-4.32).
Conclusions: Maternal nitrosatable drug use in pregnancy increases risk of astrocytoma, hepatoblastoma, and germ cell tumors in offspring in our study. The findings underscore the importance of further exploration into the potential carcinogenic effects of maternal nitrosatable drug use in pregnancy on offspring.