Overview 

One of the biggest health concerns in the world today is Cancer. Amongst its varied forms, Stomach cancer or Gastric cancer is particularly lethal due to its high death rate and often late-stage detection.¹

Out of the variety of stomach cancer risk factors identified, Alcohol use has drawn a lot of interest.  Time and again, Research has shown the possible involvement of alcohol in the onset and spread of this malignancy.^2,3

This article explains the link between alcohol and stomach cancer by looking at biological mechanisms, epidemiological data, and preventative strategies.

Epidemiology of stomach cancer

According to the estimation of GLOBOCAN 2020, stomach cancer is the fifth most common cancer in the world.⁴ In 2020, around 1.1 million new cases were diagnosed, causing 800,000 deaths.⁴ It is ranked as the fourth leading cause of death in both genders.⁵

The rate of occurrence of stomach cancer was found to be higher in East Asia, Eastern Europe, and portions of Central and South America.⁵ Etiology of this cancer depends on a variety of factors, including genetic vulnerability, Helicobacter pylori infection, dietary practices, and environmental factors like exposure to alcohol and smoke.^6,7

Alcohol consumption is a major environmental risk factor, and its association with stomach cancer highlights the need for public health campaigns to reduce alcohol use, especially in high-risk areas. Additionally, understanding global patterns of alcohol use is essential to grasp its impact on gastric cancer development.

Worldwide alcohol use and its role in carcinogenesis  

Around the world, lots of people drink alcohol. The intake differs significantly between geographical regions and cultures. While drinking in moderation is fine, excessive drinking leads to serious health risks.

The 2019 World Health Organisation (WHO)  report estimated that 400 million people lived with alcohol and drug use disorders globally.⁸ Of this, 209 million people lived with alcohol addiction. It contributes to over 3 million deaths each year, accounting for 5.3% of all deaths globally.⁹

Excessive alcohol consumption is linked to cancer aetiology. It was listed as a carcinogen by the International Agency for Research on Cancer (IARC) in 1988.¹⁰

Since then, alcohol has been linked to cancers of the oral cavity¹¹ and pharynx, oesophagus¹², stomach^13, etc. In 2014, a study found that people who drink alcohol are at a higher risk of stomach cancer, with a relative risk of 1.21.¹³

Despite these risks, public awareness about the link between alcohol consumption and cancer is relatively low. Health organisations should address the risks associated with alcohol consumption to reduce the global burden of alcohol-related diseases and cancers.

Understanding the link between alcohol and stomach cancer

Extensive research has been done over the years to understand the relationship between alcohol consumption and stomach cancer.  A meta-analysis published in Oncotarget reported a risk ratio of 1.21, indicating that each 10 g/day increase in alcohol intake raised gastric cancer risk by 7%.¹³

This dose-dependent relationship has been further confirmed by another study, which found that individuals consuming three or more alcoholic drinks per day had a higher risk than non-drinkers.¹⁴ Studies also suggest that it is the ethanol content that primarily increases the cancer risk. and not the type of alcoholic beverage.¹⁵

Mechanisms behind alcohol’s role in carcinogenesis

Understanding the biological mechanisms by which alcohol influences stomach cancer development is crucial:

• DNA Damage: Alcohol is metabolised in the body to acetaldehyde, a toxic and carcinogenic compound. This binds to DNA in stomach cells, initiating gene mutations and leading to malignancy in the gastric mucosa.¹⁶

Ratna A, Mandrekar P. Alcohol and Cancer: Mechanisms and Therapies. Biomolecules. 2017 Aug 14;7(3):61.

• Genetic Variability: Alcohol is digested in our body by the enzyme aldehyde dehydrogenase (ADH) to acetaldehyde. In some individuals, due to genetic polymorphisms of the gene encoding ADH, there is an increased concentration of acetaldehyde in the stomach.¹⁷ This causes DNA damage and inflammation in the stomach lining, which is the precursor state of cancer
• Acetaldehyde Hybrid Adducts:  Other than directly damaging the DNA, Acetaldehyde can also react with molecules, such as malondialdehyde, to form adducts. When these attach to cellular proteins, they lead to oxidative stress, lipid peroxidation, and DNA damage. Stomach mucosa gets damaged, and the likelihood of malignant transformation increases, contributing to the development of gastric cancer¹⁸
• CYP2E1 Pathway Activation: Chronic drinking induces the CYP2E1 enzyme pathway, which leads to the production of more acetaldehyde and reactive oxygen species (ROS) in the stomach.¹⁹ These increase inflammation and DNA damage in stomach cells, making them more susceptible to malignancy
• Disruption of Retinoid Signalling:  Alcohol accelerates CYP2E1 enzyme activation. This enzyme pathway breaks down retinoic acid (which plays an important role in regulating cell differentiation) into retinoids. Retinoids interact with various signalling pathways, promoting abnormal growth and proliferation of stomach cells. This ultimately increases the risk of gastric cancer^20,21
• Weakening of Immune Surveillance: Too much alcohol consumption weakens the immune surveillance mechanisms in the stomach. As a result, the body's ability to detect and destroy tumour cells in the gastric lining is affected, allowing pre-cancerous or cancerous cells to proliferate unchecked, ultimately leading to the development of stomach cancer²²
• Synergy of H. pylori and alcohol: H.pylori infection causes chronic inflammation and damages the gastric mucosa. If Alcohol is added to this mix, they both act in synergy to worsen the situation. Ethanol in itself can irritate the gut lining, making it easier for the H. pylori to colonise the gastric mucosa. Furthermore, the acetaldehyde and ROS, which are the metabolites of alcohol, can cause DNA damage in the already H. pylori-inflamed gastric tissues, thereby creating a conducive environment for cancer²³

Alcohol disrupts the immune system in different ways to accelerate tumour development. Understanding these immune reactions in detail is crucial for developing therapeutic strategies.

Strategies to lower alcohol-linked gastric cancer risk

Given the established link between alcohol consumption and stomach cancer, several preventive strategies are advisable:

• Moderation in Alcohol Intake: Limiting alcohol consumption is the best preventive measure. Health guidelines often recommend that men limit their intake to two standard drinks per day and women to one standard drink per day. However, some health organisations advocate for even lower limits or complete abstinence to minimise cancer risk^24,25
• Public Health Policies: Introducing public health policies such as increasing taxes on alcoholic beverages, restricting advertising, and providing public education on the risks associated with alcohol can help reduce binge drinking and thereby cancer risks²⁶
• Regular Medical Check-Ups: For individuals with other risk factors for stomach cancer, such as a family history or H. pylori infection, regular medical screenings are essential for early detection and intervention^27,28

Summary

Due to its high death rate and delayed diagnosis, Stomach (gastric) cancer continues to be a major global health concern. Alcohol consumption is been recognised as one of the risk factors for gastric carcinogenesis. According to a Meta-analysis study, the risk of stomach cancer increases by 7% with each 10 g/day increase in alcohol consumption. It is the ethanol and not the beverage, to blame.

In the body, alcohol is metabolised into acetaldehyde. This binds to DNA, causes mutations, and promotes oxidative stress. Additionally, gene polymorphism of the alcohol-metabolising enzymes may raise the risk by increasing acetaldehyde levels.

Alcohol also activates the CYP2E1 pathway, leading to the production of reactive oxygen species, which disrupt retinoid signalling and weaken immune surveillance.

Furthermore, alcohol synergises with Helicobacter pylori infection, enhancing inflammation and DNA damage in the stomach lining.

Limiting alcohol intake, educating the public about the risk factors, and screening high-risk individuals are some of the ways by which we can reduce the alcohol associated risk factors of stomach cancer.