Genetic risk score
To build a GRS for sorafenib, we estimated the genetic profiles of patients depending on frequencies of genotypes and alleles of examined gene polymorphisms. For each SNP, a score of 0 was defined for homozygous non-responder alleles, 1 for heterozygous responder and non-responder alleles, and 2 for two homozygous responder alleles.22-24 The response-increasing alleles were attributed based on their greater frequency in response subjects according to the literature data for angiogenesis-related genes9-11,25 and by data obtained in the present study for ADME-related genes. For each subject, a combined GRS was calculated as the sum of these response-increasing alleles; the score was 0-10 for 5 variants.