It has been shown that SRY-box Transcription Factor 2 (Sox2), one of the most frequent gene amplified in esophagus squamous cell carcinoma, leads to the development of tumors in the forestomach but not in the esophagus, when overexpressed in mouse foregut epithelium.9 This difference relies at least partially on the level of inflammation and signal transducer and activator of transcription 3 (Stat3) expression, which is higher in the forestomach and promotes carcinogenesis.9 On one hand, this observation highlights the influence of the microenvironment on cancer initiation. The gene discussed is STAT3; the disease is esophageal squamous cell carcinoma.