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RESEARCH PRODUCT
A comprehensive study of polymorphisms in the ABCB1, ABCC2, ABCG2, NR1I2 genes and lymphoma risk.
Daniele CampaKatja ButterbachSusan L. SlagerChristine F. SkibolaSilvia De SanjoséYolanda BenaventeNikolaus BeckerLenka ForetovaMarc MaynadiePierluigi CoccoAnthony StainesRudolf KaaksPaolo BoffettaPaul BrennanLucia CondePaige M. BracciNeil E. CaporasoSara S. StromNicola J. CampJames R. CerhanGec ConsortiumFederico CanzianAlexandra Nieterssubject
Cytoplasmic And Nuclear ReceptorTechnologyCancer ResearchReceptors SteroidAbcg2Chronic lymphocytic leukemiaGeneBCL9Risk FactorsXenobioticATP Binding Cassette Transporter Subfamily G Member 2Poisonmultidrug resistance protein 2AlleleGeneticseducation.field_of_studyPregnane X receptorB-Cell Chronic Lymphocytic LeukemiabiologyMultidrug resistance-associated protein 2pregnane x receptorMultiple Drug ResistanceMultidrug Resistance-Associated Protein 2Neoplasm Proteinsmultidrug resistance 1Oncologybreast cancer resistance proteinMultidrug Resistance-Associated ProteinsCase-Control StudieBreast NeoplasmMultidrug Resistance-Associated ProteinsB-Cell LymphomaATP Binding Cassette Transporter Subfamily BATP-Binding Cassette TransporterMaintenancePopulationPopulationSingle-nucleotide polymorphismlymphomaPolymorphism Single NucleotideArticlemedicineHumansGenetic Predisposition to DiseaseATP Binding Cassette Transporter Subfamily B Member 1educationRegulator GeneHematologic NeoplasmProteinsmedicine.diseaseHaplotypeslymphoma; multidrug resistance 1; multidrug resistance protein 2; breast cancer resistance protein; pregnane x receptorSingle Nucleotide Polymorphismbiology.proteinNeoplasmATP-Binding Cassette Transportersdescription
Owing to their role in controlling the efflux of toxic compounds, transporters are central players in the process of detoxification and elimination of xenobiotics, which in turn is related to cancer risk. Among these transporters, ATP-binding cassette B1/multidrug resistance 1 (ABCB1/MDR1), ABCC2/multidrug resistance protein 2 (MRP2) and ABCG2/breast cancer resistance protein (BCRP) affect susceptibility to many hematopoietic malignancies. The maintenance of regulated expression of these transporters is governed through the activation of intracellular "xenosensors" like the nuclear receptor 1I2/pregnane X receptor (NR1I2/PXR). SNPs in genes encoding these regulators have also been implicated in the risk of several cancers. Using a tagging approach, we tested the hypothesis that common polymorphisms in the transporter genes ABCB1, ABCC2, ABCG2 and the regulator gene NR1I2 could be implicated in lymphoma risk. We selected 68 SNPs in the four genes, and we genotyped them in 1,481 lymphoma cases and 1,491 controls of the European case-control study (EpiLymph) using the Illumina GoldenGate® assay technology. Carriers of the SNP rs6857600 minor allele in ABCG2 was associated with a decrease in risk of B-cell lymphoma (B-NHL) overall (p < 0.001). Furthermore, a decreased risk of chronic lymphocytic leukemia (CLL) was associated with the ABCG2 rs2231142 variant (p = 0.0004), which could be replicated in an independent population. These results suggest a role for this gene in B-NHL susceptibility, especially for CLL. Copyright © 2011 UICC.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2011-11-28 |