Suo C, Qing T, Liu Z, et al. - Researchers undertook this population-based case-control study to evaluate the risk of esophageal squamous cell carcinoma (ESCC) in correlation with family history of esophageal cancer as well as SNPs. They quantified the cumulative genetic risk by constructing a Genetic Family-history-related Risk (GFR) and non-Family-history-related Risk score. These scores were developed for 1,041 patients and 1,764 controls by genotyping 87 genetic variants. With a higher GFR score, a rise in ESCC risk was evident. The highest GFR score group among the subgroup with a positive family history displayed a nearly seven-fold higher risk of ESCC. In the stratum without a family history, the corresponding estimate was only two-fold. At age 75, the cumulative risk of esophageal cancer in 4 subgroups as defined by first-degree relatives of cases or controls with high or low genetic risk score was estimated to be 13.3%, 10.2%, 8.2% and 5.1%, respectively, in a reconstructed cohort analysis. A higher cumulative risk was seen in the cohort of relative of ESCC cases with low genetic risk score vs the cohort of relative of controls with high genetic risk score, showing the major role of environmental factors. Overall, preventive strategies to screen certain genetic polymorphisms, particularly in people with a family history, are required.