There are a lot of studies to regarding the assocation between ALDH2 deficiency and oral cancer risk. I think part of the issue is that
AFR people are less likely to become alcoholics, or to drink alcohol at all.
Japanese in particular have a high proportion of ALDH2 polymorphism, leading to subclinical but still biologically significant levels of acetaldehyde increase after drinking among the non-AFR group.
Drinking even small amounts of alcohol when you have AFR is really really bad for cancer risk.
Note that ALDH2 deficiency homozygotes would have the highest levels of post-drinking acetaldehyde but have the lowest levels of oral cancer because almost none of them drink. As in, out of ~100 homozygotes, only 2 were recorded as light drinkers, and none as heavy drinkers. This may be survival bias as the definition of heavy drinking may literally kill them.
The source for #4 looks like a pretty good meta-study, but some of the tables are off by one for some reason. Might just be on my end.
ADH polymorphism is also pretty common in Asian populations, generally in the direction of increased activity. This results in faster conversion of ethanol to acetaldehyde, but often isn’t included in these studies. This isn’t really relevant for this discussion though.
As always, biostatistics is hard! If X causes less drinking, drinking contributes to cancer, and X increases drinking’s effects on cancer, X may have positive, neutral, or negative overall correlation with cancer. Most studies I’ve looked at had a pretty string correlation between ALDH2 deficiency and cancer though, especially after you control for alcohol consumption.
It also looks like most researchers in the field think the relationship is causal, with plausible mechanisms.
The Alcohol Flushing Response: An Unrecognized Risk Factor for Esophageal Cancer from Alcohol Consumption—PMC (nih.gov)
There are a lot of studies to regarding the assocation between ALDH2 deficiency and oral cancer risk. I think part of the issue is that
AFR people are less likely to become alcoholics, or to drink alcohol at all.
Japanese in particular have a high proportion of ALDH2 polymorphism, leading to subclinical but still biologically significant levels of acetaldehyde increase after drinking among the non-AFR group.
Drinking even small amounts of alcohol when you have AFR is really really bad for cancer risk.
Note that ALDH2 deficiency homozygotes would have the highest levels of post-drinking acetaldehyde but have the lowest levels of oral cancer because almost none of them drink. As in, out of ~100 homozygotes, only 2 were recorded as light drinkers, and none as heavy drinkers. This may be survival bias as the definition of heavy drinking may literally kill them.
The source for #4 looks like a pretty good meta-study, but some of the tables are off by one for some reason. Might just be on my end.
ADH polymorphism is also pretty common in Asian populations, generally in the direction of increased activity. This results in faster conversion of ethanol to acetaldehyde, but often isn’t included in these studies. This isn’t really relevant for this discussion though.
As always, biostatistics is hard! If X causes less drinking, drinking contributes to cancer, and X increases drinking’s effects on cancer, X may have positive, neutral, or negative overall correlation with cancer. Most studies I’ve looked at had a pretty string correlation between ALDH2 deficiency and cancer though, especially after you control for alcohol consumption.
It also looks like most researchers in the field think the relationship is causal, with plausible mechanisms.