Carcinogenesis Advance Access published online on February 17, 2005
Carcinogenesis, doi:10.1093/carcin/bgi035
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1 Division of Digestive Endoscopy and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan; Division of Head and Neck Surgery, National Cancer Center Research Institute East, Kashiwa, Japan
* To whom correspondence should be addressed. While multiple squamous cell carcinomas both in the esophagus and the head and neck region are often observed and puzzle us about the favorable treatments, the reason why some patients are more likely to develop multiple cancers remains obscure. To assess the risk of multiple cancers for the establishment of an effective prevention and screening programs, we statistically analyzed clinical factors in 204 patients with newly diagnosed squamous cell carcinoma. Widespread epithelial oncogenic alterations were assessed as multiple lugol-voiding lesions (multiple LVL) by lugol chromoendoscopy. Genetic polymorphisms of alcohol dehydrogenase type 3 (ADH3) and aldehyde dehydrogenase type 2 (ALDH2) were identified by PCR-restriction-fragment-length polymorphism analysis. Forty patients had synchronous multiple cancers and the remaining 163 had solitary cancer. Presence of multiple LVL was the only independent risk factor for multiple cancers (relative risk [RR] = 67; 95%CI, 15-310). Multiple LVL was observed in only smoking-drinkers. Among them, multivariate analysis demonstrated that the ALDH2 deficiency allele (RR = 5.7; 95% CI, 2.8-11.6) and the slow-metabolizing ADH3 allele (RR = 1.9; 95% CI, 1.1-7.9) were the independent risk factors for multiple LVL. Combination of these alleles leaded to increase the risk of multiple LVL. In conclusion, episode of multiple LVL is a remarkable high risk of multiple cancers both at the esophagus and the head and neck region. The interaction between drinking and the ALDH2 deficiency allele increase the risk. In addition, the slow-metabolizing ADH3 allele enhances the risk. Prohibiting alcohol and early detection are strongly recommended for such individuals.
Received November 13, 2004
Revised January 1, 2005
Accepted January 24, 2005
CARCINOGENESIS
Risk of multiple squamous cell carcinomas both in the esophagus and the head and neck region
Manabu Muto, E-mail: mmuto{at}east.ncc.go.jp
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