Mean corpuscular volume, alcohol flushing, and the predicted risk of squamous cell carcinoma of the esophagus in cancer-free Japanese men

Background: Because some of the causes of increased mean corpuscular volume (MCV) and esophageal squamous cell carcinoma (ESCC), including alcoholism, acetaldehyde exposure, smoking, and poor nutrition are common to both, macrocytosis has been used as a predictor of early ESCC in Japanese alcoholics. We examined whether this was also true in the Japanese general population. Methods: This study compared the MCV of 522 cancer-free Japanese men with his risk of ESCC as defined using drinking, smoking, dietary habits and aldehyde dehydrogenase-2 (ALDH2) genotype in a previous case-control study of ESCC involving them as control subjects. Results: MCV was significantly correlated with ESCC risk predicted by drinking combined with ALDH2 genotype, smoking, or fruit intake. Men at higher risk of ESCC were more frequent in the groups with higher MCV (p < 0.0001 for trend). The replies to a questionnaire about facial flushing in response to alcohol showed that the trend was more prominent in men with current/former flushing, a surrogate marker for inactive ALDH2, than in men with no flushing (p < 0.0001). In comparison with the mean risk of men with MCV ≤ 93 fl (lowest quartile), that of current/former flushing men with MCV ≥ 99 fl (highest quartile) was 6.35-fold higher, whereas that of never-flushing men with MCV ≥ 99 fl was 6.35-fold higher. The sensitivity and specificity of the combination of moderate-to-heavy drinking and either MCV ≥ 99 fl or current/former flushing, either 30+ pack-years or MCV ≥ 99 fl or either 30+ pack-years or current/former flushing for detection of high-risk persons ranking in the top 10%, was 85% and 84%, 94% and 76%, or 98% and 77%, respectively. Conclusions: MCV and alcohol flushing might be used to better select candidates to screen this high-mortality-rate cancer not only in alcoholics but also in nonalcoholic Japanese men.