Introduction:
The study focuses on how alcohol and genetics simultaneously increase the chances of developing oral cancer, specifically in Japanese men. Cancers in the oropharyngeal regions (esophagus and throat) are strongly linked to alcohol consumption; however, some individuals are more susceptible than others. As an increase in esophageal cancer has been observed in Japan, it is important to understand why. A gene prevalent in East Asians known as ALDH2*2 is a mutant allele that encodes an inactive form of the enzyme Aldehyde Dehydrogenase-2. In specifically Japanese alcoholic patients, this inactive form has been seen to cause an increase in cancer in the upper aerodigestive tract. ALDH2 affects the body’s process to break down alcohol, which, if paired with alcohol consumption, detrimentally affects the rate at which cancer can be formed. The study explores how inactive forms of ALDH2 can correlate with higher chances of developing oral cancer if paired with alcohol consumption.
Methods:
The study observed two sample groups: one group that consisted of Japanese drinkers with esophageal squamous cell carcinomas (ESCC), and one group of Japanese drinkers without ESCC. To keep the experimental constant and controlled, age, drinking, and smoking habits were adjusted so that the effect of ALDH2 could be examined without the influence of external factors. Comparing Japanese drinkers with or without ALDH2 to alcohol consumption allowed researchers to examine how the development of single or multiple cancers is related to genetic differences and alcohol metabolism.
Results:
Japanese males with an inactive ALDH2 gene displayed a higher risk of developing multiple cancers, reporting a 2-10x higher risk than Japanese males with the active form of the ALDH2 gene. Specifically, the prevalence of multiple esophageal and head/neck cancers was notably higher in those with ALDH2 deficiency, where heavy drinkers with this genotype had the highest incidence of synchronous (simultaneous) or metachronous (over time) cancers. Rather than only showing a general increase in cancer risk, the findings point more specifically to a pattern of cancer multiplicity, meaning these individuals were more likely to develop cancers at more than one site or at different times. The results suggest that inactive ALDH2 may be linked not just to cancer occurrence, but to a broader susceptibility of the upper aerodigestive tract in men who drink alcohol.
Conclusion:
ALDH2 gene deficiency correlates with higher rates of developing various cancer types if alcohol consumption is also accounted for. Specifically, East Asian men are more vulnerable to having an inactive ALDH2 gene, where the study shows that individuals with this deficiency who drink alcohol are more likely to develop multiple cancers in the esophagus and throat.
