Natural history of liver fluke infection underpins epidemiological patterns of biliary cancer
A partir de l'analyse de l'évolution des infections par la douve du foie dans la population thaïlandaise et en s'appuyant sur les transformations hépatiques observées après ces infections ainsi que l'évolution de l'incidence du cholangiocarcinome, cette étude démontre comment l'exposition à des pathogènes peut influencer les modèles épidémiologiques des cancers
Infestation with parasitic worms can cause cancer in humans, though this decades-long process is challenging to study. Here, we show how liver fluke ecology determines the epidemiology of cholangiocarcinoma (bile duct cancer) in Thailand. We first characterize the natural history of infection. People are exposed by consuming raw freshwater fish before ten years of age, and worms survive for 13 y inside humans. The earliest driver mutations emerge at 30 y old, which is three decades before cancer diagnosis and provides a window for preventative treatment. We calculate that 5% of infected people acquire cholangiocarcinoma, which is fourteen times higher than populations without liver fluke. Lower parasite transmission after 1990 suggests that cholangiocarcinoma incidence will decline in the future. Pathogens are major drivers of cancer globally and the processes of infection and carcinogenesis unfold over decades making them difficult to observe in human or natural populations. We investigate these hidden dynamics for the foodborne trematode Opisthorchis viverrini, which is a primary cause of biliary cancer (cholangiocarcinoma) and infects 12 million people in Southeast Asia. In tumors from patients exposed to O. viverrini, we find that the earliest chromosomal amplifications carrying driver genes occurred at 30 y old on average, two to four decades before cancer diagnosis, and disproportionately contain TP53, PTEN and FGFR2 genes. We then fitted transmission models to parasitological data from Thailand spanning 27 y (n = 11,517) finding that, for people born between 1960 and 1989, first exposure occurred at two years old and by 30 y individuals had been cumulatively infected with a median of 72 worms. Trematodes are long-lived and our analysis quantifies the average lifespan of O. viverrini as 13 y (90% credible interval [CrI] 7 to 26 y) within human hosts. The lifetime probability of diagnosis with cholangiocarcinoma is 4.9% (90% CrI 4.7 to 5.0%) given prior exposure to O. viverrini, which is fourteen-fold higher than in populations nonendemic for the parasite. We find strong evidence for a dramatic decline in parasite transmission from 1990 onward in Thailand, suggesting that the incidence of cholangiocarcinoma will decline over the coming decades. Our study demonstrates how pathogen exposure drives patterns of cancer within a population and provides evidence for public health and therapeutic interventions.
Proceedings of the National Academy of Sciences , résumé, 2025