International Journal of Community Medicine and Public Health

Reddy SD. Int J Community Med Public Health. 2024 Dec;11(12):4956-4960

http://www.ijcmph.com

pISSN 2394-6032 | eISSN 2394-6040

Meta-Analysis

DOI: https://dx.doi.org/10.18203/2394-6040.ijcmph20243668

Meta-analysis of alcohol consumption and cancer risk: a comprehensive review of epidemiological evidence and mechanistic insights

Sagam Dinesh Reddy*

Department of Family Medicine/Industrial Health, LMR Hospital, G. Konduru, Andhra Pradesh, India

Received: 14 September 2024

Revised: 19 October 2024

Accepted: 08 November 2024

*Correspondence:

Dr. Sagam Dinesh Reddy,

E-mail: dineshsagam143@gmail.com

Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Alcohol consumption has been identified as a risk factor for various types of cancer. This meta-analysis aims to quantify the association between alcohol intake and cancer risk and to explore the underlying biological mechanisms. A comprehensive literature search was conducted for studies published between January 2000 to December 2023. Eligible studies included cohort and case-control studies that reported relative risks (RRs) or odds ratios (ORs) for cancer associated with alcohol consumption. Data were extracted and pooled using a random-effects model. Heterogeneity was assessed using the I² statistic. Subgroup analyses were performed based on cancer type and level of alcohol consumption. A total of 75 studies were included in the meta-analysis. Alcohol consumption was significantly associated with an increased risk of several cancers, including those of the oral cavity, pharynx, esophagus, liver, breast, and colorectum. The pooled RRs for high vs. low/no alcohol consumption were as follows: oral cavity and pharynx (RR=3.15, 95% CI: 2.44-4.05), esophagus (RR=2.89, 95% CI: 2.19-3.81), liver (RR=1.83, 95% CI: 1.39-2.40), breast (RR=1.25, 95% CI: 1.14-1.37), and colorectum (RR=1.21, 95% CI: 1.09-1.34). Heterogeneity was moderate to high across studies. This meta-analysis confirms the significant association between alcohol consumption and increased risk of multiple cancers. Public health strategies should emphasize reducing alcohol intake to lower cancer risk.

Keywords: Alcohol drinking, Neoplams, Carcinogenesis, Acetaldehyde, Oxidative stress

INTRODUCTION

Alcohol consumption is a common lifestyle factor with significant public health implications. While moderate alcohol intake has been associated with certain cardiovascular benefits, its relationship with cancer risk has raised concerns. The international agency for research on cancer (IARC) classifies alcoholic beverages as group 1 carcinogens, underscoring the need to understand this association comprehensively. This meta-analysis aims to quantify the risk of various cancers associated with alcohol consumption and to explore the underlying biological mechanisms.

METHODS

A comprehensive search of PubMed, EMBASE, and Cochrane Library databases was conducted for studies published between January 2000 and December 2023. The search terms included "alcohol," "cancer," "risk," "cohort study," and "case-control study."

Inclusion criteria

Cohort or case-control studies, studies reporting RRs or ORs for cancer associated with alcohol consumption and studies published in English were included.

Exclusion criteria

Reviews, editorials, or case reports, studies with insufficient data for meta-analysis and duplicate publications were excluded.

Data extraction

Two reviewers independently extracted data, including study characteristics (author, year, country, study design), participant characteristics (age, gender), type of cancer, alcohol consumption levels, and RRs or ORs with 95% confidence intervals (CIs).

Statistical analysis

Pooled RRs and the 95% CIs were calculated using the random-effects model. Heterogeneity among studies was assessed using the I² statistic.

Subgroup analyses were performed based on cancer type and alcohol consumption levels. Publication bias was evaluated using funnel plots and Egger's test.

RESULTS

Study characteristics

A total of 75 studies met the inclusion criteria, comprising 45 cohort studies and 30 case-control studies.

The studies included a total of 2,500,000 participants and 120,000 cancer cases.

Table 1: Characteristics of included studies.
Table reproduced from source PDF page 2, part 1 of 2
Table reproduced from source PDF page 3, part 2 of 2

Pooled risk estimates

The pooled RRs for high vs. low/no alcohol consumption were as follows:

Table 2: Pooled RRs for cancer types.
Table reproduced from source PDF page 3

Subgroup analysis

Subgroup analyses showed that the risk was higher for certain cancers with increasing levels of alcohol consumption.

Figure 1: Dose-response relationship between alcohol consumption and cancer risk.
Figure 1: Dose-response relationship between alcohol consumption and cancer risk.
Figure 2: Funnel plot for publication bias assessment.
Figure 2: Funnel plot for publication bias assessment.

Heterogeneity and publication bias

Moderate to high heterogeneity was observed across studies (I² ranging from 45% to 70%). Funnel plot asymmetry and Egger's test suggested potential publication bias.

DISCUSSION

This meta-analysis provides robust evidence that alcohol consumption is associated with an increased risk of multiple cancers. The biological mechanisms underlying this association include:

Metabolism of alcohol to acetaldehyde

Alcohol is metabolized in the liver by alcohol dehydrogenase (ADH) enzymes to acetaldehyde, a highly reactive and toxic compound. Acetaldehyde can form DNA adducts, causing mutations and inhibiting DNA repair mechanisms, leading to carcinogenesis.

Oxidative stress

Alcohol metabolism generates reactive oxygen species (ROS) and other free radicals. These ROS can damage cellular components, including lipids, proteins, and DNA, leading to mutations and promoting cancer development.

Chronic inflammation

Chronic alcohol consumption can lead to persistent inflammation in various tissues. Inflammatory responses can produce cytokines and other mediators that promote cellular proliferation, inhibit apoptosis, and increase the risk of cancer.

Hormonal changes

Alcohol consumption can alter hormone levels, particularly estrogens. Elevated estrogen levels can promote the development of hormone-sensitive cancers, such as breast cancer, by increasing cellular proliferation and inhibiting programmed cell death.

Nutritional deficiencies

Alcohol interferes with the absorption and metabolism of various nutrients, including vitamins and minerals. Deficiencies in nutrients like folate can impair DNA synthesis and repair, leading to an increased risk of cancer.

Immune suppression

Chronic alcohol use can suppress the immune system. A weakened immune system is less effective at identifying and destroying cancer cells, allowing for tumor development and progression.

Epigenetic changes

Alcohol consumption can lead to epigenetic modifications, such as DNA methylation and histone modification. These changes can alter gene expression patterns, silencing tumor suppressor genes and activating oncogenes.

CONCLUSION

Our meta-analysis confirms that alcohol consumption is a significant risk factor for various cancers. The mechanisms by which alcohol promotes carcinogenesis include the metabolism of alcohol to acetaldehyde, oxidative stress, chronic inflammation, hormonal changes, nutritional deficiencies, immune suppression, and epigenetic changes. Public health interventions should focus on reducing alcohol consumption to lower the burden of alcohol-related cancers. Further research is needed to explore these biological mechanisms in more detail and to develop targeted prevention strategies.

Funding: No funding sources

Conflict of interest: None declared

Ethical approval: Not required

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