Carcinogenesis Advance Access originally published online on February 17, 2005
Carcinogenesis 2005 26(5):1008-1012; doi:10.1093/carcin/bgi035
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Carcinogenesis vol.26 no.5 © Oxford University Press 2005; all rights reserved.
Risk of multiple squamous cell carcinomas both in the esophagus and the head and neck region
Division of Digestive Endoscopy and Gastrointestinal Oncology and 1 the Division of Head and Neck Surgery, National Cancer Center Hospital East, 6-5-1 kashiwanoha Kashiwa, 277-8577 Japan and 2 National Cancer Center Research Institute East, Kashiwa, Japan
* To whom correspondence should be addressed Email: mmuto{at}east.ncc.go.jp
While multiple squamous cell carcinomas are often observed in the esophagus and the head and neck region and confound us about the favorable treatments, the reason why some patients are more likely to develop multiple cancers remains obscure. We statistically analyzed clinical factors in 203 patients with newly diagnosed squamous cell carcinoma, to assess the risk of multiple cancers for the establishment of an effective prevention and screening programs. Widespread epithelial oncogenic alterations were assessed as multiple lugol-voiding lesions (multiple LVL) using 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, a 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 lead to increase the risk of multiple LVL. In conclusion, an episode of multiple LVL is a remarkable high risk for multiple cancers both at the esophagus and the head and neck region. The interaction between drinking and the ALDH2 deficiency allele increases the risk. In addition, the slow metabolizing ADH3 allele enhances the risk. Prohibiting the use of alcohol and early detection of cancer are strongly recommended for such individuals.
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