Journal Article

Macrocytosis, a new predictor for esophageal squamous cell carcinoma in Japanese alcoholic men

Akira Yokoyama, Tetsuji Yokoyama, Taro Muramatsu, Tai Omori, Sachio Matsushita, Susumu Higuchi, Katsuya Maruyama and Hiromasa Ishii

in Carcinogenesis

Volume 24, issue 11, pages 1773-1778
Published in print November 2003 | ISSN: 0143-3334
Published online November 2003 | e-ISSN: 1460-2180 | DOI:
Macrocytosis, a new predictor for esophageal squamous cell carcinoma in Japanese alcoholic men

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  • Clinical Cytogenetics and Molecular Genetics


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Early esophageal squamous cell carcinoma detected by esophageal iodine staining can be easily treated by endoscopic mucosectomy, and identifying its predictors is important in better selecting candidates to screen for this high-mortality cancer. The common etiologies of elevated mean corpuscular volume (MCV) and esophageal cancer, including folate deficiency, smoking, drinking and high acetaldehyde exposure, suggest testing MCV as such a predictor. 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. MCV was higher in cancer patients than in the control group. MCV was higher in both groups in those who were heavier smokers, had lower body mass index (BMI), experienced alcohol flushing, and had ALDH2*1/2*2. After adjusting for age, drinking and smoking habits, BMI and ALDH2/ADH2 genotypes, macrocytosis of MCV ≥106 fl was associated with increased risk for esophageal cancer (OR = 2.75). Men with both MCV ≥106 fl and alcohol flushing had an even higher cancer risk (OR = 5.51). The combinations of MCV ≥106 fl with ALDH2*1/2*2 or ADH2*1/2*1 alone, and both ALDH2*1/2*2 and ADH2*1/2*1 (ORs = 11.44, 21.22 and 319.7, respectively) showed consistently higher risk than the corresponding group with MCV <106 fl (ORs = 7.24, 4.71 and 27.01, respectively). In conclusion, MCV measurement, alone or in combination with the markers of alcohol sensitivity, provides a new means of predicting risk for esophageal squamous cell carcinoma in Japanese alcoholic men.

Keywords: ADH, alcohol dehydrogenase; ALDH, aldehyde dehydrogenase; BMI, body mass index; LSM, least square mean; MCV, mean corpuscular volume; OR, odds ratio; ROC, receiver operating characteristic

Journal Article.  4547 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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