After adjusting for age and substance use, adjusted ORs in the betel chewing group increased from 22.45 (95% CI, 13.39–37.64) for HNSCC, to 31.55 (95% CI, 13.00–76.60) for NOTCH1 without SMs, and to 32.11 (95% CI, 10.41–99.05) for NOTCH1 with SMs. The gene discussed is NOTCH1; the disease is head and neck squamous cell carcinoma.