LAUSR

Most existing genotype-phenotype association studies in cancer recases, the protective factor implicitly referred to the derived (i.e. the search were designed to detect cancer-causing (pathogenic) genetic variants, i.e., those showing strong linkage with cancer susceptibility, but rarely to focus on the protective variants. In the current issue of EBioMedicine, Zhu et al. [1] explored the impact of single nucleotide polymorphisms (SNPs) within base excision repair (BER) genes on the Wilms tumor susceptibility, based on 145 cases and 531 healthy controls from Chinese Han children. They concluded that three SNPs, hOGG1 rs1052133, FEN1 rs174538 and rs4246215, showed protective effects against Wilms tumor, a common pediatric kidney cancer. Since this is the first time to investigate the association between BER polymorphisms andWilms tumor risk, the conclusions brought new knowledge and insights into the field. This pioneer work also addressed (at least partially) the current paucity of research pertaining to the protective effects of gene SNPs against human cancer. Complete information about overall risk-modifying variants, including both cancer-risk and cancer-preventive ones, facilitates better genetic definition of population subgroups and potentially expedites personalized treatment according to their genetic profiles [2, 3]. The current work represents a good example to report cancer-protective variants in a particular population with clinical translational potential. This potential is further consolidated by a previous relevant study, in which one of the currently studied SNP, hOGG1 rs1052133, was reported to be a strong protective factor for head and neck squamous cell carcinomas among north Indian populations [4]. More encouragingly, owing to the continuing progress in the next-generation sequencing technologies and high-throughput genotyping platforms, it is becomingmore feasible and efficient to pursue such goals than ever before. Similar work aiming to identify general human disease-protective variants has been emerging, including those targeting breast cancer [5], type 2 diabetes, multiple sclerosis and rheumatoid arthritis [6]. Therefore, efforts towards identification and characterization of diseaseprotective SNPs would be increasingly promising in the near future. When talking about a protective variant, one point should be clarified. The statement that a SNP showed protective effects against tumor is inaccurate, and subjects to a conceptual and semanticsmistake. Every disease-associated SNP involves two alleles, with one considered “risk-associated” and the other by default referred to as “disease-protective”. In the context of the current paper, and as presumed in general