Association of aldehyde dehydrogenase 2 gene polymorphism with multiple oesophageal dysplasia in head and neck cancer patients.
BACKGROUND
Multiple occurrences of oesophageal dysplasia are frequently observed in head and neck cancer patients, and closely associated with alcohol consumption. Acetaldehyde, the first metabolite of ethanol, is thought to play an important role in the carcinogenesis of the upper aerodigestive tract.


OBJECTIVE
To investigate if genetic polymorphism in alcohol metabolising enzymes (ADH3, alcohol dehydrogenase 3; ALDH2, aldehyde dehydrogenase 2) is associated with oesophageal multiple dysplasia in head and neck cancer patients.


METHODS
Thirty one consecutive patients with head and neck cancer were included in the study. Multiple oesophageal dysplasia was detected endoscopically as multiple Lugol voiding lesions (multiple LVL) using the Lugol dye staining method. The ADH3 and ALDH2 genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism.


RESULTS
Among the 31 patients with head and neck cancer, 17 had multiple LVL. Multiple LVL were closely associated with a second primary oesophageal carcinoma in head and neck cancer patients (odds ratio 60.7, 95% CI 5.6-659). Furthermore, the mutant ALDH2 allele was significantly more prevalent in patients with multiple LVL (65% v 29%; p<0.05) whereas no difference was observed in ADH3 polymorphism.


CONCLUSIONS
The mutant ALDH2 allele appears to be a risk indicator for multiple LVL in head and neck cancer patients. Accumulation of acetaldehyde due to low ALDH2 activity may play a critical role in cancerous changes throughout the mucosa in the upper aerodigestive tract.
Muto
M
M
Department of Gastrointestinal Oncology and Gastroenterology, National Cancer Center Hospital East, Kashiwa, Japan. mmuto@aest.ncc.go.jp
Hitomi
Y
Y
Ohtsu
A
A
Ebihara
S
S
Yoshida
S
S
Esumi
H
H
D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000483:Alleles; D004938:Esophageal Neoplasms / Q000201:enzymology*; D005260:Female; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000201:enzymology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D016609:Neoplasms, Second Primary / Q000201:enzymology; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011230:Precancerous Conditions / Q000201:enzymology*; D013194:Staining and Labeling
D009363:Neoplasm Proteins; C030863:corneal protein 54, bovine; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial