Drinkers that cannot efficiently breakdown alcohol due to a genetic mutation have a higher risk of stomach cancer. That is the conclusion of a recently published meta-analysis1. The influence of the genetic mutation on the risk of stomach cancer is higher for moderate and heavy drinkers compared to non to rare drinkers.
What is already known? The World Cancer Research Fund indicates that three or more alcoholic consumptions a day (45 grams alcohol) probably increases the risk of stomach cancer2. Previous studies that take mutations of the ALDH2 gene into account have inconsistent results1.
What does this study add? The meta-analysis looks at the influence of specific genetic mutations on the relation between alcohol consumption and stomach cancer. The study includes 7 case-control studies with around 3,300 stomach cancer patients and 4,900 controls (participants without stomach cancer).
Important enzyme for alcohol breakdown
The current study looks at the effect of specific mutations in the ALDH2 gene that encodes an enzyme called aldehyde dehydrogenase (ALDH). This enzyme plays an important role in the breakdown process of alcohol. It makes sure that the toxic intermediate breakdown product of alcohol, called acetaldehyde, is converted into acetate: a compound which can be safely metabolized in the body.
Some people, especially in East Asia, have a mutation in this gene. This means that the enzyme is inactive and does not work properly. People with such a mutation cannot drink a lot of alcohol, because they get hangover-like symptoms such as flushing and nausea in reaction to the build-up of acetaldehyde.
Higher risk with inactive gene
Results show that moderate to high alcohol consumption (more than 5 drinks a week) is related to a higher risk of stomach cancer. Looking at the specific genetic mutations, the risk is higher for people with an inactive ALDH2 enzyme. As the authors expected, alcohol consumption increases the risk for stomach cancer more in those with inactive ALDH2 than those with active ALDH2 enzymes.
Considering that the risk of stomach cancer in moderate to heavy drinkers with inactive ALDH2 was twice fold, the authors recommend strict abstinence for people with this mutation to reduce the risk of stomach cancer.
Despite a worldwide decline, stomach cancer remains a common cause of cancer death3. In 2018 the percentage of cancer deaths due to stomach cancer was 5,3%4. The incidence remains high in East Asia. An important risk factor of stomach cancer is an infection of Helicobacter pylori. But also lifestyle factors play a role. Apart from alcohol, smoking, high salt intake, and vitamin C deficiency seem to increase the risk5,6.
- Taken into account the polymorphisms of the ALDH2 gene
- Alcohol consumption before the survey could not be accurately identified
- Drinking pattern not included
- Not adjusted for ex-drinkers
- Did not account for Helicobacter pylori infection
- Joo Kang, S., Shin, C. M., Sung, J., & Kim, N. (2020). Association Between ALDH2 Polymorphism and Gastric Cancer Risk in Terms of Alcohol Consumption: A Meta‐Analysis. Alcoholism: Clinical and Experimental Research.
- World Cancer Research Fund International/American Institute for Cancer Research. Continuous Update Project Report: Diet, Nutrition, Physical Activity and Stomach Cancer. 2016.
- Balakrishnan, M., George, R., Sharma, A., & Graham, D. Y. (2017). Changing Trends in Stomach Cancer Throughout the World. Current gastroenterology reports, 19(8), 36. https://doi.org/10.1007/s11894-017-0575-8
- The Cancer Atlas. The burden – Europe. Accessed at 28 January 2021.
- Ladeiras-Lopes, Ricardo, et al. Smoking and gastric cancer: systematic review and meta-analysis of cohort studies. Cancer Causes & Control. 2008;19(7):689-701.
6. Tsugane S and Sasazuki S. Diet and the risk of gastric cancer: review of epidemiological evidence. Gastric Cancer. 2007;10(2):75-83.