Available online 1 June 2023

Author links open overlay panel, , , , , AbstractBackground

East Asian populations, where alcohol consumption is rising, has a high prevalence of the inactivated aldehyde dehydrogenase-2 (ALDH2) enzyme involved in alcohol metabolism. This study estimates the burden of alcohol-attributable cancer accounting for genotype-specific cancer risk and alcohol exposure.

Methods

We conducted a systematic review and meta-analysis of eight databases on cancer risk to derive alcohol dose-response curves by ALDH2 genotype. A simulation-based approach using the Global Burden of Disease modelling framework was applied to estimate the population attributable fraction (PAF), incidence, and disability-adjusted life- years (DALYs) lost to alcohol-attributable cancer.

Findings

We included 34 studies (66,655 participants) from China, Japan, and South Korea in the meta-analysis. Alcohol dose-response curves for liver, oesophageal, and oral cavity/pharynx cancer showed an increased risk for people with the inactivated ALDH2 genetic polymorphism, resulting in a higher burden of alcohol-attributable cancer compared to GBD estimates. Our methods estimated annual incidence of cancer of 230,177 cases, an underestimate of 69,596 cases compared to GBD estimates. Similarly, total DALYs lost annually was underestimated by 1.20 million.

Interpretation

The burden of liver, oesophageal, and oral cavity/pharynx cancer attributable to alcohol is underestimated in populations with the ALDH2 genetic polymorphism when compared to current estimates.

Funding

Health and Medical Research Fund, Health Bureau, Government of the Hong Kong SAR (20211791).

Section snippetsINTRODUCTION

Alcohol consumption is a leading preventable cause of ill-health, injuries and mortality, adversely impacting 13 of the 17 United Nations Sustainable Development Goals (SDGs) [1]. Consumption of alcohol has a causal role in cancers of the upper aerodigestive tract (oral cavity, pharynx, larynx, and esophagus), liver, breast, and colorectum [2], [3]. An estimated 741,300 (4.1%) new cancer cases were attributable to alcohol in 2020 [4].

People with the aldehyde dehydrogenase-2*2 (ALDH2*2) genetic

METHODS

The analysis was registered with international prospective register of systematic reviews (PROSPERO) CRD42021229402; and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA 2020) guidelines (see Supporting Information for PRISMA checklist). No patients were involved in this study.

Risk of cancer for ALDH2*2 carriers

Our search identified 8,258 studies, with 10 identified through other sources (Figure S1). After duplicates were removed, the titles and abstracts of 4,618 articles were screened, 428 full text articles were reviewed, and 49 studies were included in the qualitative review. The included studies (48 case-control, 1 cohort) comprised of 87,649 participants from four countries: China, Japan, Thailand, and South Korea. After quality assessment, we excluded 15 studies of low quality (NOS score less

DISCUSSION

Our study estimated the national, regional, and global burden of alcohol-attributable cancer adjusting for the ALDH2 genotype, that inhibits alcohol metabolism, prevalent in East Asian populations. We found the risk of liver, esophageal, lip and oral cavity, nasopharyngeal and pharyngeal cancer for ALDH2*2 carriers were higher than non-carriers at a comparable level of alcohol exposure. GBD estimates show East Asia already has the highest absolute burden and PAF of alcohol-attributable cancers

Ethics approval and consent to participate

Ethics approval and consent to participate in this research article were waived as this study used secondary data.

Consent for publication

Not applicable

CRediT authorship contribution statement

JCQ and CSN conceived and designed the study. XJO and MA conducted the systematic search and selected studies for inclusion. MA, XJO, YHL and HHYK extracted the data and graded the quality of the evidence. CSN analyzed the data with support from XJO and MA. CSN and JCQ interpreted the data and wrote the first draft. CSN, XJO and MA verified the data. JCQ acquired funding. All authors read and approved the final draft.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

Not applicable

Competing interests

The authors declare that they have no competing interests.

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