Pathogens are major drivers of cancer globally. Quantifying the relationship between infection and carcinogenesis is therefore crucial for developing preventative programs. The foodborne trematode Opisthorchis viverrini is a primary cause of biliary cancer (cholangiocarcinoma) and infects 12 million people in Southeast Asia. In tumours from patients exposed to O. viverrini we found that the earliest chromosomal amplification of driver genes occurred at 30 years old on average, two to four decades before cancer diagnosis, and disproportionately contained FGFR2, TP53 and PTEN genes. We fitted transmission models to parasitological data from Thailand spanning 27 years (n = 11,517) finding that, for people born between 1960–1989, first exposure occurred at two years old and by 30 years 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 years (90% credible interval [CrI] 6–23 years) within human hosts. Finally, we calculate the lifetime probability of diagnosis with cholangiocarcinoma as 1.2% (90% CrI 1.0–1.4%) given prior exposure to the parasite.

C.B. received honoraria as speaker (AstraZeneca, Incyte) and consultant (Incyte, Servier, Boehringer Ingelheim, AstraZeneca, Jazz Therapeutics, Tahio), received research funds (Avacta, Medannex, Servier) and her spouse is an employee of AstraZeneca. The other authors declare no competing interests.

T.C. acknowledges that this research was funded in whole, or in part, by the Wellcome Trust [Grant number 215919/B/19/Z]. C.B. acknowledges that this study was performed under the collaborative umbrella of the European Network for the Study of Cholangiocarcinoma (EURO CHOLANGIO NET) supported by COST action (CA) 18122 and the Precision BTC network supported by CA22125. P.S. acknowledges funding from the National Research Council of Thailand as part of the Fluke Free Thailand program.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committee/IRB of the University of Glasgow, College of Medical, Veterinary and Life Sciences waived ethical approval for this work on the basis that this study uses data approved via established governance mechanisms, uses secondary or existing data, and raises no new ethical concerns.

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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Code and publicly available data to reproduce the analysis are available at https://github.com/tc13/ov-cca-models. Access to sequence data on biliary cancer genomes is controlled by the International Cancer Genome Consortium Data Access Compliance Office (ICGC DACO).

https://github.com/tc13/ov-cca-models