ABSTRACT
Lapatinib is a clinically important component of the treatment for HER2-positive metastatic breast cancer and has an acceptable safety profile. Lapatinib-associated Hy's Law cases have been characterized using human leukocyte antigen (HLA) DQA1*02:01/DRB1*07:01 and Gilbert's syndrome UGT1A1*28/*28 genotypes. The HLA-positive cases had higher alanine aminotransferase (ALT) elevation, whereas the HLA-negative cases had a higher incidence of Gilbert's syndrome. The findings of our study, which extend this HLA association to lapatinib-associated serious liver injury, emphasize the importance of Gilbert's syndrome in the interpretation of Hy's Law and may lead to methods for enhancing patient safety.
Subject(s)
Chemical and Drug Induced Liver Injury/genetics , Gilbert Disease/genetics , Glucuronosyltransferase/genetics , HLA-DQ alpha-Chains/genetics , HLA-DRB1 Chains/genetics , Quinazolines/adverse effects , Alanine Transaminase/biosynthesis , Alanine Transaminase/genetics , Chemical and Drug Induced Liver Injury/epidemiology , Chemical and Drug Induced Liver Injury/immunology , Genotype , Gilbert Disease/drug therapy , Gilbert Disease/immunology , Glucuronosyltransferase/biosynthesis , HLA-DQ alpha-Chains/biosynthesis , HLA-DRB1 Chains/biosynthesis , Humans , Incidence , LapatinibABSTRACT
HL-A antigens were determined in 18 unrelated patients with Gilbert's syndrome and 3 families where this condition occurred in 2 generations. The data obtained do not point out an association between HL-A antigens and Gilbert's syndrome.
