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No association between MDR1 (ABCB1) 2677G>T and 3435C>T polymorphism and sporadic colorectal cancer among Bulgarian patients

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Abstract

Purpose

Variation in genetic factors together with xenobiotic exposure may result in increased risk of colorectal cancer. The P-glycoprotein (P-gp) is highly expressed in the apical membrane of enterocytes, where it pumps xenobiotics from the enterocytes back into the intestinal lumen. Thus, polymorphisms that reduce the activity of the MDR1 (ABCB1) efflux pump are potential risk factors for colorectal carcinogenesis. The aim of the present study is to genotype the MDR1 2677G>T (rs2032582) and 3435C>T (rs1045642) polymorphism in patients with colorectal cancer and controls and to identify a possible association between individual genetic variation and susceptibility to colorectal cancer.

Methods

In the present study, 146 Bulgarian patients with sporadic colorectal cancer and 160 healthy Bulgarian volunteers were evaluated for the two polymorphisms in MDR1. Polymorphisms were identified using rapid-cycle real-time amplification with allele-specific probes and subsequent melting curve analyses on a LightCycler™ (Roche Diagnostics, Mannheim, Germany).

Results

No differences were found between the frequencies of the two mutant alleles in the tumor tissue from the cases and lymphocytes from the controls [frequencies of 2677T: 43.5% in patients and 44.1% in controls; frequencies of 3435T: 48.3% in patients and 50.9% in controls (both P > 0.05)]. The MDR1 polymorphic sequence of the tumor tissue always matched that of normal intestinal tissue from the same patient. Consequently, genotyping of DNA from archived tumor tissues is a valid alternative to the use of leukocyte DNA.

Conclusions

The present study suggests that MDR1 2677G>T and 3435C>T polymorphism is not a risk factor for sporadic colon cancer among Bulgarians and that somatic mutation at these sites is not involved in the genesis of colon tumors. Further examination using larger number of samples must be necessary to reach to more reliable conclusions.

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Acknowledgments

We thank Ekaterina Ilieva for her technical assistance. This study was supported by EUROGENDIS, Maria Curie Fellowship Contract No. QLGA-CT-2000-60005, IPSS-Research Centre for Drug Development, Germany, and Ministry of Education and Science, Bulgaria (Project INP 01.OR.2005), and by the Ministry of Education and Science of Bulgaria, Upgrading of Research Infrastructure Grant No. 05/01.08.2005.

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Authors and Affiliations

  1. Department of Medical Genetics, Medical University Sofia, 2, Zdrave Str., 1431, Sofia, Bulgaria

    Darinka Todorova Petrova & Draga Toncheva

  2. Department of Pathology, Specialized Oncological Hospital, Veliko Tarnovo, Bulgaria

    Petya Nedeva

  3. Department of Surgery, Specialized Oncological Hospital, Veliko Tarnovo, Bulgaria

    Svilen Maslyankov

  4. Department of Surgery, Aleksandrovska University Hospital, Sofia, Bulgaria

    Svetoslav Toshev & Nikolay Yaramov

  5. Department of Clinical Chemistry, Georg-August-University, Göttingen, Germany

    Srebrena Atanasova, Michael Oellerich & Nicolas von Ahsen

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  1. Darinka Todorova Petrova
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Correspondence to Draga Toncheva.

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Petrova, D.T., Nedeva, P., Maslyankov, S. et al. No association between MDR1 (ABCB1) 2677G>T and 3435C>T polymorphism and sporadic colorectal cancer among Bulgarian patients. J Cancer Res Clin Oncol 134, 317–322 (2008). https://doi.org/10.1007/s00432-007-0279-9

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