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Liver Cancer Etiology: Old Issues and New Perspectives

  • REVIEW
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Abstract

Purpose of Review

This review aims to synthesize the old issues and current understandings of the etiology of liver cancer, focusing on the diverse causative factors influenced by geographical, socioeconomic, and lifestyle variations across different regions.

Recent Findings

We highlight significant geographic disparities in liver cancer risk factors. While hepatitis B and C viruses, aflatoxin exposure, and alcohol consumption remain globally established contributors; metabolic dysfunction-associated steatotic liver disease and metabolic syndromes are increasingly prominent in the West. Chronic HBV and aflatoxin continue to dominate as risk factors in Asia and Africa. Dietary factors, metabolic diseases like diabetes and obesity, genetic predispositions, environmental risk factors and lifestyle choices such as smoking and alcohol use play substantial roles in specific populations. Protective factors like coffee and tea consumption, along with aspirin use, vegetables and fruits have shown potential in reducing HCC risk, although findings vary by population and dietary habits.

Summary

Liver cancer etiology is influenced by various factors that differ by region. Established risk factors include hepatitis B and C, aflatoxin, and alcohol. Emerging risks, such as metabolic dysfunction-associated steatotic liver disease, are more prevalent in Western countries, while aflatoxin and HBV remains significant in Asia and Africa. Diet, metabolic conditions like diabetes and obesity, genetic predispositions, and lifestyle choices also play crucial roles. Coffee, tea, aspirin, vegetables, and fruits may reduce HCC risk, but effectiveness varies. Future research should integrate epidemiology, genetics, and nutrition, with global cooperation and data sharing essential for effective cancer control strategies.

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Data Availability

No datasets were generated or analysed during the current study.

Abbreviations

PLC:

Primary liver cancer

HCC:

Hepatocellular carcinoma

ASMR:

Age-standardized mortality rate

ASIR:

Age-standardized incidence rate

AAPC:

Average annual percentage change

SDI:

Social demographic index

UHCI:

Universal health coverage index

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

AF:

Aflatoxin

NAFLD:

Non-alcoholic fatty liver disease

MASLD:

Metabolic dysfunction-associated steatotic liver disease

NASH:

Non-alcoholic steatohepatitis

MASH:

Metabolic dysfunction associated steatohepatitis

DM:

Diabetes mellitus

GBD:

Global burden of disease

HBsAg:

Hepatitis B surface antigen

HDV:

Hepatitis D virus

HEV:

Hepatitis E virus

DALY:

Disability-adjusted life year

OR:

Odds ratio

CLD:

Chronic liver disease

SES:

Socioeconomic status

PAF:

Population attributable fraction

T2DM:

Type 2 diabetes mellitus

EDIP:

Empirical dietary inflammation pattern

EDIH :

Empirical dietary index for hyperinsulinemia

BC:

Black carbon

NDEA :

N-Nitrosodiethylamine

NDMA :

N-Nitrosodimethylamine

SHBG :

Sex hormone-binding globulin

HR :

Hazard ratio

UPDP :

Urban prudent dietary pattern

TCDP :

Traditional Cantonese dietary pattern

MPFP :

High meat and pickled food pattern

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Funding

This study was funded by the National Key Research and Development Program of China (Grant No. 2021YFC2500405).

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Authors and Affiliations

  1. Qidong Liver Cancer Insititute, Qidong People’s Hospital, Affiliated Qidong Hospital of Nantong University, Qidong, 226200, People’s Republic of China

    Jian-Guo Chen, Yong-Hui Zhang & Jian-Hua Lu

  2. Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA

    Thomas W. Kensler

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  1. Jian-Guo Chen
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  2. Yong-Hui Zhang
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  4. Thomas W. Kensler
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All authors contributed to the paper conception. Material preparation and data collection were performed by YHZ, JHL and JGC. The first draft of the manuscript was written by JGC. The final manuscript was critically revised by JGC and TWK. All authors read and approved the final manuscript.

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Correspondence to Jian-Guo Chen or Thomas W. Kensler.

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Chen, JG., Zhang, YH., Lu, JH. et al. Liver Cancer Etiology: Old Issues and New Perspectives. Curr Oncol Rep 26, 1452–1468 (2024). https://doi.org/10.1007/s11912-024-01605-7

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