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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,10,14]]},"abstract":"<jats:p>\n                    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\n                    <jats:italic toggle=\"yes\">Opisthorchis viverrini<\/jats:italic>\n                    , which is a primary cause of biliary cancer (cholangiocarcinoma) and infects 12 million people in Southeast Asia. In tumors from patients exposed to\n                    <jats:italic toggle=\"yes\">O. viverrini<\/jats:italic>\n                    , 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\n                    <jats:italic toggle=\"yes\">TP53<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">PTEN<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">FGFR2<\/jats:italic>\n                    genes. We then fitted transmission models to parasitological data from Thailand spanning 27 y (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\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\n                    <jats:italic toggle=\"yes\">O. viverrini<\/jats:italic>\n                    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\n                    <jats:italic toggle=\"yes\">O. viverrini<\/jats:italic>\n                    , 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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2423536122","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:22:47Z","timestamp":1760113367000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":3,"title":["Natural history of liver fluke infection underpins epidemiological patterns of biliary cancer"],"prefix":"10.1073","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2934-1063","authenticated-orcid":false,"given":"Thomas","family":"Crellen","sequence":"first","affiliation":[{"name":"Saw Swee Hock School of Public Health","place":["Singapore, Singapore"]},{"name":"National University of Singapore","place":["Singapore, Singapore"]},{"name":"Big Data Institute","place":["Oxford, United Kingdom"]},{"name":"Li Ka Shing Centre for Health Information and Discovery","place":["Oxford, United Kingdom"]},{"name":"University of Oxford","place":["Oxford, United Kingdom"]},{"name":"Nuffield Department of Medicine","place":["Oxford, United Kingdom"]},{"name":"Centre for Tropical Medicine and Global Health","place":["Oxford, United Kingdom"]},{"name":"University of Oxford","place":["Oxford, United Kingdom"]},{"name":"School of Biodiversity One Health and Veterinary Medicine","place":["Glasgow, United Kingdom"]},{"name":"University of Glasgow","place":["Glasgow, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Vita","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences","place":["Glasgow, United Kingdom"]},{"name":"Wolfson Wohl Cancer Research Centre","place":["Glasgow, United Kingdom"]},{"name":"University of Glasgow","place":["Glasgow, United Kingdom"]},{"name":"Department of Oncology","place":["Turin, Italy"]},{"name":"University of Turin","place":["Turin, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Braconi","sequence":"additional","affiliation":[{"name":"School of Cancer Sciences","place":["Glasgow, United Kingdom"]},{"name":"Wolfson Wohl Cancer Research Centre","place":["Glasgow, United Kingdom"]},{"name":"University of Glasgow","place":["Glasgow, United Kingdom"]},{"name":"Beatson West of Scotland Cancer Centre","place":["Glasgow, United Kingdom"]},{"name":"Cancer Research UK Scotland Cancer Centre","place":["Glasgow, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9480-1778","authenticated-orcid":false,"given":"Paiboon","family":"Sithithaworn","sequence":"additional","affiliation":[{"name":"Department of Parasitology","place":["Khon Kaen, Thailand"]},{"name":"Faculty of Medicine","place":["Khon Kaen, Thailand"]},{"name":"Khon Kaen University","place":["Khon Kaen, Thailand"]},{"name":"Cholangiocarcinoma Research Institute","place":["Khon Kaen, Thailand"]},{"name":"Khon Kaen University","place":["Khon Kaen, Thailand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. 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