title: A comprehensive study of polymorphisms in the ABCB1, ABCC2, ABCG2, NR1I2 genes and lymphoma risk.
abstract: 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.
authors.affiliation: Genomic Epidemiology Group, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Daniele
authors.initials: D
authors.lastname: Campa
authors.forename: Katja
authors.initials: K
authors.lastname: Butterbach
authors.forename: Susan L
authors.initials: SL
authors.lastname: Slager
authors.forename: Christine F
authors.initials: CF
authors.lastname: Skibola
authors.forename: Silvia
authors.initials: S
authors.lastname: de Sanjosé
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Benavente
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Becker
authors.forename: Lenka
authors.initials: L
authors.lastname: Foretova
authors.forename: Marc
authors.initials: M
authors.lastname: Maynadie
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Cocco
authors.forename: Anthony
authors.initials: A
authors.lastname: Staines
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.forename: Lucia
authors.initials: L
authors.lastname: Conde
authors.forename: Paige M
authors.initials: PM
authors.lastname: Bracci
authors.forename: Neil E
authors.initials: NE
authors.lastname: Caporaso
authors.forename: Sara S
authors.initials: SS
authors.lastname: Strom
authors.forename: Nicola J
authors.initials: NJ
authors.lastname: Camp
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
authors.forename: Alexandra
authors.initials: A
authors.lastname: Nieters
mesh_terms: 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*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008223:Lymphoma / Q000145:classification / Q000235:genetics*; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000235:genetics*; D012307:Risk Factors
chemical_list: 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; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human; C116614:ABCG2 protein, human; C000625852:NR1I2 protein, human