ALDH2 deficiency or hypochlorhydria was more prevalent in ESCC compared with controls and both showed increased independent associations with ESCC in multivariate analysis.
A dataset composed of 4,220 cases and 8,946 controls from twelve studies of Asian populations was analyzed for ADH1B Arg47His association with ESCC and its interactions with alcohol drinking and ALDH2Glu504Lys.
Alcohol consumption combined with inactive aldehyde dehydrogenase-2 (ALDH2) and the presence of multiple esophageal Lugol-voiding lesions (LVLs; dysplasia) are strong predictors for multiple development of esophageal squamous cell carcinoma (ESCC) in East Asians.
An elevation of the risk for ESCC was pronounced most among carriers of ALDH2 Lys/Lys and XRCC1 399Gln/Gln or Gln/Arg who consumed a low level of dietary selenium (adjusted OR, 4.16; 95% CI, 1.14-15.12).
Asian case-control studies have shown a strong relationship between the development of squamous cell carcinoma (SCC) of the esophagus and alcohol consumption combined with inactive aldehyde dehydrogenase-2 (ALDH2*1/*2), less-active alcohol dehydrogenase-1B (ADH1B*1/*1), high mean corpuscular volume (MCV), and self-reported facial flushing in response to alcohol.
Furthermore, persons with the combined genotypes ADH2(1)/ADH2(1) and ALDH2(1)/ALDH2(2) were at extraordinarily high risk for esophageal squamous cell carcinoma, with an odds ratio of 17.9 (p < 0.001).
Heavy alcohol consumption in individuals with ALDH2 gene polymorphism significantly elevates the risk of ESCC, however, effective prevention has not been established yet.
In conclusion, male sex and the ALDH2-2 allele are associated with an increased risk for multiple LVLs of the esophageal mucosa in patients with esophageal squamous cell carcinoma.
In our previous study, we found that polymorphisms of alcohol and aldehyde dehydrogenase (ADH1B and ALDH2) are important risks for esophageal squamous cell carcinoma in a Taiwanese population.
In the chromosome 12q24 locus, ALDH2rs671 (G>A) is related to the susceptibility to ESCC in Kazak populations, and it is also associated with poor prognosis of EC in Kazak and Han populations.
In the Mixed Ancestry population, ALDH2 +82 G > A (rs886205) was significantly associated with a reduced risk of OSCC (odds ratio = 0.70, 95% confidence interval = 0.55-0.89; P = 0.0038).
Increased risk of ESCC was suggested in ALDH2 for frequency of presence C allele of SNP [Rs886205: 1.626 (1.158-2.284)], XPD for C allele [Rs50872: 1.482 (1.058-2.074)], and MGMT for A allele [Rs11016897: 1.666 (1.245-2.228)].
Japanese alcoholic men with (n = 65) and without (n = 206) esophageal squamous cell carcinomas, excluding those with liver cirrhosis, were assessed for MCV within 7 days of their last drink, alone or in combination with findings from either the alcohol flushing questionnaire or genotyping to identify inactive aldehyde dehydrogenase-2 (ALDH2*1/2*2) and the less-active form of alcohol dehydrogenase-2 (ADH2*1/2*1), which pose risks for esophageal squamous cell carcinoma.
Patients with inactive ALDH2, in whom facial flushing is usually observed after the drinking of alcohol, are at high risk for ESCC as well as multiple UADT cancers.
Previously, we identified that rs1229984 in ADH1B, rs671 in ALDH2, and smoking status were independently associated with the risk of developing metachronous squamous cell carcinoma (SCC) after endoscopic resection (ER) for esophageal SCC (ESCC).
Risk alleles of rs1229984 (ADH1B) and rs671 (ALDH2) were highly associated with OSCC (odds ratio (OR)=4.08, p=4.4×10(-40) and OR=4.13, p=8.4×10(-76), respectively).
The ALDH2 Lys and XRCC1 Gln variant alleles were associated with an increased risk of ESCC with adjusted ORs of 1.91 (95% CI, 0.96-3.80) and 1.67 (95% CI, 1.08-2.59), respectively.
The ADH1B, ADH1C and ALDH2 gene polymorphisms influence the risk of OSCC through modulation of acetaldehyde metabolism and propensity to alcohol intake.
The genetic variations of ADH1B His47Arg and ALDH2Glu487Lys are susceptible loci for ESCC in Chinese Han population and interact substantially with alcohol consumption.
The inactive ALDH2 encoded by ALDH2*1/*2 and the less-active ADH1B encoded by ADH1B*1/*1 increase the risk of esophageal squamous cell carcinoma in East Asian drinkers.