A comprehensive study of polymorphisms in the ABCB1, ABCC2, ABCG2, NR1I2 genes and lymphoma risk

Daniele Campa, Katja Butterbach, Susan L. Slager, Christine F. Skibola, Silvia De Sanjosé, Yolanda Benavente, Nikolaus Becker, Lenka Foretova, Marc Maynadie, Pierluigi Cocco, Anthony Staines, Rudolf Kaaks, Paolo Boffetta, Paul Brennan, Lucia Conde, Paige M. Bracci, Neil E. Caporaso, Sara S. Strom, Nicola J. Camp, James R. CerhanGec Consortium, Federico Canzian, Alexandra Nieters

Research output: Contribution to journalArticle

27 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)803-812
Number of pages10
JournalInternational Journal of Cancer
Volume131
Issue number4
DOIs
StatePublished - Aug 15 2012

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Keywords

  • breast cancer resistance protein
  • lymphoma
  • multidrug resistance 1
  • multidrug resistance protein 2
  • pregnane x receptor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Campa, D., Butterbach, K., Slager, S. L., Skibola, C. F., De Sanjosé, S., Benavente, Y., Becker, N., Foretova, L., Maynadie, M., Cocco, P., Staines, A., Kaaks, R., Boffetta, P., Brennan, P., Conde, L., Bracci, P. M., Caporaso, N. E., Strom, S. S., Camp, N. J., ... Nieters, A. (2012). A comprehensive study of polymorphisms in the ABCB1, ABCC2, ABCG2, NR1I2 genes and lymphoma risk. International Journal of Cancer, 131(4), 803-812. https://doi.org/10.1002/ijc.26436