Drinking and blushing is a genetic disease that greatly increases the risk of cancer. Will gene therapy be a savior?

Whether it is joys and sorrows, or separation and reunion, wine is never absent.
People will drink to celebrate when they are happy, and when they are sad, they will use wine to dissipate their sorrows
.

For Asians, whether they can drink or the harmfulness of drinking can be easily judged by whether they blush after drinking, because the phenomenon of blushing after drinking often only occurs among Asians.
This phenomenon is also called " Asian Red"
.

The proportion of East Asian populations carrying ALDH2 homozygous mutations is as high as 25%, while other regions are very rare

The reason why some people blush when drinking is because they carry a genetic mutation-ALDH2 gene mutation, 35-45% of Asians carry this genetic mutation
.

More importantly, acetaldehyde is a carcinogen.
People who drink alcohol and blush frequently will greatly increase the risk of digestive system cancers such as esophageal cancer and gastric cancer
.

Epidemiological investigations have shown that people who drink and blush (carrying ALDH2 homozygous mutations) and often drink alcohol have an increased risk of esophageal cancer by 7-12 times
.

From these findings, drinking and blushing can be regarded as a common genetic disease that increases the risk of cancer due to ALDH2 gene mutations
.

In recent years, gene therapy has made brilliant achievements in the field of cancer and genetic diseases.
So, can gene therapy be used to prevent and save the risk of cancer caused by drinking and blushing?

As shown in the figure above, the liver is the main metabolic site of ethanol (alcohol).
In the liver, alcohol dehydrogenase converts ethanol into acetaldehyde, and acetaldehyde dehydrogenase 2 (ALDH2) converts acetaldehyde into non-toxic Acetate
.

As early as October 2017, the U.
S.
Food and Drug Administration (FDA) approved Spark Therapeutics' AAV gene therapy, which uses adeno-associated virus (AAV) as a delivery vehicle to deliver RPE65 gene to patients with congenital amaurosis The retina of blind patients with type 2 disease allows them to regain light
.

For people carrying ALDH2 homozygous mutations, they cannot produce functional acetaldehyde dehydrogenase 2 in their body.
If the correct ALDH2 gene is delivered to the body through the AAV viral vector, it can produce acetaldehyde dehydrogenase activity, thereby preventing alcohol.
Later acetaldehyde accumulates to prevent potential carcinogenic effects
.

In December 2019, researchers from Weill Cornell College of Medicine published a research paper titled: Gene Therapy Correction of Aldehyde Dehydrogenase 2 Deficiency in the journal Molecular Therapy: Methods & Clinical Development
.

The research team used AAV rh.
10h to deliver the human ALDH2 gene to mice lacking ALDH2 gene for experiments.
The results showed that compared with the control group, the mouse liver after the gene therapy treatment continued to produce acetaldehyde dehydrogenase 2 , Acetaldehyde levels decreased significantly after alcohol intake, and abnormal behaviors related to alcohol intake were also significantly improved
.

Interestingly, there are some studies hoping to inhibit the activity of ALDH2, because many people have high ALDH2 activity, and drinking alcohol will not cause symptoms such as blushing and headaches, which makes them prone to alcoholism
.

For those who have ALDH2 homozygous gene mutations and often drink alcohol, if they have developed esophageal precancerous lesions, then they are very likely to develop esophageal cancer.
For these people, increase their ALDH2 activity through AAV gene therapy It is a feasible gene therapy strategy to prevent it from developing into esophageal cancer
.

Generally speaking, ALDH2 gene mutations are widespread in Asians, which causes them to blush easily after drinking, and also greatly increases their risk of digestive system cancer
.