Synergistic interaction of ABCB1 and ABCG2  polymorphisms predicts the prevalence of toxic  encephalopathy during anticancer  chemotherapy.
Polymorphisms of the ABCB1 (MDR1) and ABCG2 (BCRP) genes were reported to alter the expression and function of these drug transporters. Both proteins are present at the main pharmacokinetic barriers including the blood-brain barrier. Data from 291 children with acute lymphoblastic leukaemia were analysed in this retrospective study. ABCB1 3435T>C, 2677G>T/A, 1236C>T and ABCG2 421C>A, 34G>A genotypes were determined. Encephalopathy episodes were more frequent among those with ABCB1 3435TT genotype than in the 3435CC/CT group (odds ratio (OR) 3.5; P=0.03). Patients with the ABCG2 421A allele tended to have more complications than wild type homozygotes (OR=2.0; P=0.25). The rate of the adverse effect was similar in those harbouring no or only one of the predisposing genotypes, that is, either ABCB1 3435TT or ABCG2 421AA/AC. However, significantly more children suffered encephalopathy in the group with both predisposing genotypes (OR=12.3; P=0.005). In conclusion, these variations exert synergistic effect in predisposing patients to toxic neurological complications of chemotherapy.
Erdilyi
D J
DJ
Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary. erddan@gmail.com
Kámory
E
E
Csókay
B
B
Andrikovics
H
H
Tordai
A
A
Kiss
C
C
Filni-Semsei
A
A
Janszky
I
I
Zalka
A
A
Fekete
G
G
Falus
A
A
Kovács
G T
GT
Szalai
C
C
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000483:Alleles; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002675:Child, Preschool; D015331:Cohort Studies; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D020258:Neurotoxicity Syndromes / Q000453:epidemiology / Q000209:etiology*; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics; D015995:Prevalence
C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins