Suo C, Qing T, Liu Z, et al. - By performing this population-based case–control analysis, researchers examined the link between family history of esophageal cancer, SNPs, and esophageal squamous cell carcinoma (ESCC) risk. They also quantified the cumulative number of risk genotypes carried by each individual, by constructing a genetic family history–related risk (GFR) score and non–family history-related risk score. Data from patients with nonfamilial ESCC (n = 700), familial ESCC (n = 341), controls without a family history of esophageal cancer (n = 1,445), and controls with a family history (n = 319) were analyzed. Findings revealed an increased ESCC risk in relation to a higher GFR score. The highest GFR score group among the familial subgroup had an approximately 7-fold higher risk of ESCC. In those without a reported family history of esophageal cancer, the corresponding estimate was only 2-fold higher risk of ESCC. In four subgroups, as defined by first-degree relatives of cases or controls with high or low genetic risk score, the estimated combined risk to develop esophageal cancer by age 75 years was 13.3%, 10.2%, 8.2%, and 5.1%, respectively. Especially, a higher cumulative risk was observed in the cohort of relatives of ESCC cases with low genetic risk score vs the cohort of relatives of controls with high genetic risk score. A major role of environmental factors was suggested in esophageal cancer. In order to scrutinize the mechanisms of shared environmental and genetic susceptibility influencing the risk of developing ESCC, further investigations are justified.