Genetic factors affecting drug disposition in Asian cancer patients

In the era of genomic medicine, it is increasingly recognized that ethnogeographic differences in drug pharmacology exist between Asian and other populations. This is particularly pertinent to oncology, where drugs forming the backbone of chemotherapy often have narrow therapeutic windows and are frequently dosed close to maximally tolerable levels.

At the population level, ancestry is important because historical-biogeographical confluences have shaped population genetics and pharmacoethnicity in the Asian race through allelic differentiation and interethnic differences in inheritance patterns of linkage disequilibrium. At the individual level, cis- and trans-acting germline polymorphisms and somatic mutations in genes encoding drug-metabolizing enzymes and transporters act in a multifactorial manner to determine drug disposition phenotype and clinical response in Asian cancer patients. A growing body of evidence also finds that complex genetic interactions and regulation, including a multiplicity of gene control mechanisms, are increasingly implicated in genotype-phenotype correlates than has hitherto been appreciated--potentially serving as the mechanistic links between hits in non-coding regions of genome-wide association studies and drug toxicity. Together, these genetic factors contribute to the clinical heterogeneity of drug disposition in Asian cancer patients.

This topic has broad relevance for the optimization and individualization of anticancer strategies in Asians.