The landscape of etiological patterns of hepatocellular carcinoma and intrahepatic cholangiocarcinoma in Thailand

Author:

Pupacdi Benjarath1,Loffredo Christopher A.2,Budhu Anuradha34,Rabibhadana Siritida5,Bhudhisawasdi Vajarabhongsa56,Pairojkul Chawalit6,Sukeepaisarnjaroen Wattana6ORCID,Pugkhem Ake6,Luvira Vor6,Lertprasertsuke Nirush7,Chotirosniramit Anon7,Auewarakul Chirayu U.8,Ungtrakul Teerapat8,Sricharunrat Thaniya9,Sangrajrang Suleeporn10,Phornphutkul Kannika11,Albert Paul S.12,Kim Sungduk12,Harris Curtis C.3,Mahidol Chulabhorn5,Wang Xin Wei34ORCID,Ruchirawat Mathuros513,

Affiliation:

1. Translational Research Unit Chulabhorn Research Institute Bangkok Thailand

2. Department of Oncology Georgetown University Medical Center Washington DC USA

3. Laboratory of Human Carcinogenesis, Center for Cancer Research National Cancer Institute Bethesda Maryland USA

4. Liver Cancer Program Center for Cancer Research, National Cancer Institute Bethesda Maryland USA

5. Laboratory of Chemical Carcinogenesis Chulabhorn Research Institute Bangkok Thailand

6. Faculty of Medicine Khon Kaen University Khon Kaen Thailand

7. Faculty of Medicine Chiang Mai University Chiang Mai Thailand

8. Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy Bangkok Thailand

9. Pathology and Forensic Medicine Department Chulabhorn Hospital, Chulabhorn Royal Academy Bangkok Thailand

10. National Cancer Institute Bangkok Thailand

11. Rajavej Hospital Chiang Mai Thailand

12. Biostatistics Branch, Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda Maryland USA

13. Center of Excellence on Environmental Health and Toxicology (EHT), OPS, MHESI Bangkok Thailand

Abstract

AbstractThailand is among countries with the highest global incidence and mortality rates of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). While viral hepatitis and liver fluke infections have been associated with HCC and iCCA, respectively, other environmental risk factors, overall risk factor commonality and combinatorial roles, and effects on survival have not been systematically examined. We conducted a TIGER‐LC consortium‐based population study covering all high‐incidence areas of both malignancies across Thailand: 837 HCC, 1474 iCCA, and 1112 controls (2011–2019) were comprehensively queried on lifelong environmental exposures, lifestyle, and medical history. Multivariate logistic regression and Cox proportional hazards analyses were used to evaluate risk factors and associated survival patterns. Our models identified shared risk factors between HCC and iCCA, such as viral hepatitis infection, liver fluke infection, and diabetes, including novel and shared associations of agricultural pesticide exposure (OR range of 1.50; 95% CI: 1.06–2.11 to 2.91; 95% CI: 1.82–4.63) along with vulnerable sources of drinking water. Most patients had multiple risk factors, magnifying their risk considerably. Patients with lower risk levels had better survival in both HCC (HR 0.78; 95% CI: 0.64–0.96) and iCCA (HR 0.84; 95% CI: 0.70–0.99). Risk factor co‐exposures and their common associations with HCC and iCCA in Thailand emphasize the importance for future prevention and control measures, especially in its large agricultural sector. The observed mortality patterns suggest ways to stratify patients for anticipated survivorship and develop plans to support medical care of longer‐term survivors, including behavioral changes to reduce exposures.

Funder

U.S. Department of Health and Human Services

Thailand Science Research and Innovation

Chulabhorn Research Institute

Publisher

Wiley

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