Mean corpuscular volume and ADH1C genotype in white patients with alcohol-associated diseases.
BACKGROUND
Alcohol abuse is associated with several gastrointestinal diseases, such as esophageal carcinoma, chronic alcoholic pancreatitis, and liver cirrhosis. Increased mean corpuscular volume (MCV) has been recognized as a biomarker for alcohol abuse and heavy drinkers. Recent studies from Japan revealed that macrocytosis is related to ALDH-2/2 genotype, leading to increased acetaldehyde accumulation. It has also demonstrated that increased MCV values could also be an independent biomarker for esophageal cancer in Asians. Therefore, the aim of the current study was to investigate possible associations of MCV value with polymorphisms of ADH1C in white patients with alcohol-associated esophageal carcinoma, chronic alcoholic pancreatitis, and alcoholic cirrhosis as well as in heavy drinkers without organ damage.


METHODS
In this study, a total of 510 alcoholic patients were enrolled with esophageal cancer (n = 98), chronic pancreatitis (n = 98), alcoholic liver cirrhosis (n = 151), and alcohol abuse without gastrointestinal disease (n = 163). ADH1C genotyping was performed by PCR-based restriction fragment length polymorphism (PCR-RFLP) analysis from whole blood. The relation between MCV and ADH1C gene polymorphisms (ADH1C*1 and 1C*2) controlled for the amount of drinking, smoking, and age were investigated using both univariate and multivariate analysis.


RESULTS
In univariate analysis, higher alcohol consumption was associated with increased MCV. Other variables were not associated with macrocytosis. In multiple linear regression analysis, after adjustment for age and smoking, higher alcohol consumption and female sex were independently associated with higher MCV values. No other variables, including which alcohol-associated disease the patient had, had an independent effect. Adding ADH genotype rendered no independent significant effect on MCV value.


CONCLUSIONS
In a white population, MCV values were not associated with genotype polymorphisms of ADH1C. In contrast to findings in Asians, macrocytosis does not seem to be an independent biomarker for esophageal cancer. The role of ADH1C polymorphism in increasing MCV and the potential use of MCV as a marker for esophageal carcinoma are still pending.
Sun
Leimin
L
Department of Medicine I, University Hospital of Schleswig Holstein, Campus Lübeck, Germany.
König
Inke R
IR
Jacobs
Arne
A
Seitz
Helmut K
HK
Junghanns
Klaus
K
Wagner
Thomas
T
Ludwig
Diether
D
Jacrobs
Arne
A
Homann
Nils
N
D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D020751:Alcohol-Induced Disorders / Q000097:blood* / Q000235:genetics*; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D004909:Erythrocyte Indices / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000209:etiology / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008104:Liver Cirrhosis, Alcoholic / Q000235:genetics; D008297:Male; D008875:Middle Aged; D019512:Pancreatitis, Alcoholic / Q000235:genetics; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012727:Sex Characteristics; D012907:Smoking; D044465:White People
D004247:DNA; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase