title: Genetic factors affecting drug disposition in Asian cancer patients.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  This topic has broad relevance for the optimization and individualization of anticancer strategies in Asians.
authors.affiliation: a Department of Haematology-Oncology , National University Cancer Institute , Singapore 119228.
authors.forename: Nicholas Li-Xun
authors.initials: NL
authors.lastname: Syn
authors.affiliation: a Department of Haematology-Oncology , National University Cancer Institute , Singapore 119228.|b Cancer Science Institute of Singapore , National University of Singapore, Centre for Translational Medicine , Singapore 117599.
authors.forename: Wei-Peng
authors.initials: WP
authors.lastname: Yong
authors.affiliation: a Department of Haematology-Oncology , National University Cancer Institute , Singapore 119228.|b Cancer Science Institute of Singapore , National University of Singapore, Centre for Translational Medicine , Singapore 117599.
authors.forename: Soo-Chin
authors.initials: SC
authors.lastname: Lee
authors.affiliation: a Department of Haematology-Oncology , National University Cancer Institute , Singapore 119228.|b Cancer Science Institute of Singapore , National University of Singapore, Centre for Translational Medicine , Singapore 117599.|c Department of Pharmacology, Yong Loo Lin School of Medicine , National University of Singapore , Singapore 119077.
authors.forename: Boon-Cher
authors.initials: BC
authors.lastname: Goh
mesh_terms: D000483:Alleles; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D044466:Asian People / Q000235:genetics*; D004798:Enzymes / Q000235:genetics / Q000378:metabolism; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy*; D010641:Phenotype
chemical_list: D000970:Antineoplastic Agents; D004798:Enzymes; D026901:Membrane Transport Proteins
keywords: ADME; Asian cancer patients; adverse drug events; chemotherapy; drug disposition; pharmacoethnicity; pharmacogenetics; pharmacokinetics