In addition, this HNSCC subgroup also had a significantly higher risk of developing multiple primary tumors in the upper digestive tract (OR 5.186 for ALDH2*2 and 2.093 for ADH1B*1); 84% of the HNSCC patients with multiple primary tumors in esophagus or upper GI tract had a least one ALDH2*2 allele [43]. The gene discussed is ALDH2; the disease is head and neck squamous cell carcinoma.