Background: Metachronous multiple squamous cell carcinoma (SCC) of the esophagus and the head and neck is commonly observed in patients who have previously undergone endoscopic resection (ER) for SCC of the esophagus (ESCC). We evaluated the risk for developing metachronous SCC following ER for ESCC based on the genetic polymorphisms for alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) as well as the alcohol consumption and smoking habits.
Methods: We studied 158 patients who underwent ER for ESCC (median follow-up 80 months). Genotyping of ADH1B/ALDH2 was performed using saliva sampling. The alcohol consumption and smoking histories of the patients before and after the ER were documented.
Results: Multivariate analyses revealed that inactive heterozygous ALDH2 [hazard ratio (HR) 2.25] and alcohol consumption after ER (HR 1.94) were independently associated with the risk of developing secondary SCC. Moreover, inactive heterozygous ALDH2 (HR 4.39) and alcohol consumption after the ER (HR 2.82) were independently associated with the risk of a third SCC. We analyzed 110 patients who had a history of moderate or heavy alcohol consumption before the ER. The 3-year cumulative incidence rates of secondary SCC in the temperance (n = 65) and non-temperance groups (n = 45) were 14.0 and 42.1% (p = 0.0002). Further, the 5-year cumulative incidence rates of a third SCC in the temperance and non-temperance groups were 0 and 15.6% (p = 0.0011), respectively. In addition, the 7-year cumulative incidence rates of a fourth SCC in the temperance and non-temperance groups were 0 and 15.3% (p = 0.0015), respectively.
Conclusions: Continued alcohol consumption is an important risk factor for the onset of metachronous SCC and is a risk factor for the third and subsequent SCCs. Strict advice in favor of temperance is crucial.
Keywords: Alcohol dehydrogenase1B; Aldehyde dehydrogenase2; Endoscopic resection; Esophageal cancer; Squamous cell carcinoma.