Abstract
The exposure to pesticides and toxic compounds in xenobiotic transport and metabolism genes has been shown to affect risk of developing multiple myeloma (MM). Therefore, we hypothesized that genetic variations in xenobiotic transport and metabolism regulator genes PXR (NR1I2) and CAR (NR1I3) could determine a difference in MM susceptibility. Ten tagging single-nucleotide polymorphisms (SNPs) for PXR and seven for the CAR genes were selected and genotyped in 627 MM cases and 883 controls collected in the context of the International Multiple Myeloma rESEarch (IMMEnSE) consortium. None of the 17 SNPs investigated showed significant association with MM risk either alone or when combined in haplotypes. Significant SNP–SNP interactions were not found, neither with 58 previously genotyped polymorphisms in ABC transporters. We can therefore exclude that common genetic variants in the xenobiotic transport and metabolism regulator genes PXR and CAR affect MM risk.
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Acknowledgements
We thank for the support by the recruiting hospitals and physicians of the study regions, as well as their collaborating nurses and technicians.
Author contributions
AM, DC and FC designed the study, performed the genotyping and the statistical analysis and wrote the original draft of the manuscript. AS performed the genotyping. JS, RMR, VM, GB, FL, HM, RG-S, RR, CD, FG, AMR, SL, MJ, MP and KJ recruited cases and controls and provided DNA samples and the clinical information. All the authors approved the final version submitted.
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Martino, A., Sainz, J., Manuel Reis, R. et al. Polymorphisms in regulators of xenobiotic transport and metabolism genes PXR and CAR do not affect multiple myeloma risk: a case–control study in the context of the IMMEnSE consortium. J Hum Genet 58, 155–159 (2013). https://doi.org/10.1038/jhg.2012.149
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DOI: https://doi.org/10.1038/jhg.2012.149
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