The previous report by our team regarding the association of BRCA2 p.K3326* mutation with ESCC risk [26] and our new finding of the considerable ESCC risk modifying effect of the ALDH2-rs10744777 TT genotype among BRCA2 p.K3326* carriers signify the importance of determining genetically high-risk individuals for ESCC, so that we can address individualized preventive strategies and further help to reduce ESCC incidence in northeastern Iran. Here, BRCA2 is linked to esophageal squamous cell carcinoma.