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Association of MDR1 genotypes with susceptibility to colorectal cancer in older non-smokers

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Objective

The multidrug resistance gene 1 (MDR1) seems to play a role in the carcinogenesis of colorectal tumors. The importance of MDR1 SNPs 2677G > T/A in exon 21 and 3435C > T in exon 26 for cancer susceptibility, however, has not yet been clearly defined.

Methods

Two hundred and eighty-five colorectal cancer patients and 275 controls from five hospitals in the European part of Russia were genotyped for the polymorphisms −129T > C (rs3213619) in exon 1b, 2677G > T/A (rs2032582), and 3435C > T (rs1045642) in this population-based case-control study. Genotype-phenotype analysis was performed with simultaneous consideration of lifestyle risk factors.

Results

Our analysis confirmed the preponderate impact of smoking on colorectal cancer development. The risk of heavy smokers (≥60 pack years) to develop colorectal cancer by far exceeded that of lifelong non-smokers (OR = 3.9, 95% CI: 1.4 to 10.6). Smoking is a more potent risk factor than is the genetic influence of MDR1 in our study. However, a smoking and age-stratified analysis, revealed a statistically significant association between MDR1 genotypes and colorectal cancer in life-long non-smokers with an age ≥63 years (the median age in our sample). The association was stronger for rectal cancer than for colon cancer. Patients who carried the genotypes (−129TT; 2677GG; 3435CC) or (−129TT; 2677TT; 3435TT) developed more frequently colorectal cancer than others (OR = 3.9; 95% CI: 2.0 to 7.7).

Conclusions

Our results show that the interaction of genetic and lifestyle risk factors should be taken into account to elucidate the genetic influence of MDR1 variability on cancer susceptibility.

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Acknowledgement

This study was supported by grants from the German Federal Ministry of Education and Research (BMBF) 03U1209B and 03I4507. Experiments comply with the current laws of Germany, inclusive of ethics approval.

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Authors and Affiliations

  1. Institute of Clinical Pharmacology, Charité–Universitätsmedizin Berlin, Campus Mitte, Humboldt University of Berlin, Berlin, Germany

    Elena Osswald, Andreas Johne, Gabriele Laschinski, Farhad Arjomand-Nahad, Uwe Malzahn, Julia Kirchheiner, Thomas Gerloff, Christian Meisel, Przemyslaw M. Mrozikiewicz, Ivar Roots & Karla Köpke

  2. Voronezh Burdenko State Medical Academy, Voronezh, Russia

    Elena Osswald & Jury Chernov

  3. Research Institute of Medical Plants, Poznan, Poland

    Przemyslaw M. Mrozikiewicz

  4. Cenimed, Center for Individualized Medicine GmbH, Berlin, Germany

    Gabriele Laschinski, Thomas Gerloff & Ivar Roots

  5. Institut für Klinische Pharmakologie, Charité-Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, 10117, Berlin, Germany

    Karla Köpke

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  1. Elena Osswald
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Correspondence to Karla Köpke.

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Osswald, E., Johne, A., Laschinski, G. et al. Association of MDR1 genotypes with susceptibility to colorectal cancer in older non-smokers. Eur J Clin Pharmacol 63, 9–16 (2007). https://doi.org/10.1007/s00228-006-0225-9

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  • DOI: https://doi.org/10.1007/s00228-006-0225-9

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