A polymorphism C3435T of the MDR-1 gene associated with smoking or high body mass index increases the risk of sporadic breast cancer in women

  • Authors:
    • Pavol Zubor
    • Zora Lasabova
    • Jozef Hatok
    • Andrea Stanclova
    • Jan Danko
  • View Affiliations

  • Published online on: July 1, 2007     https://doi.org/10.3892/or.18.1.211
  • Pages: 211-217
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Abstract

The human multidrug resistance gene 1 (MDR-1) encodes a plasma membrane P-glycoprotein (P-gp) that functions as the transmembrane efflux pump for various structurally unrelated anticancer agents and toxins. Polymorphisms in the MDR-1 gene may have an impact on the expression and function of P-gp, thereby influencing the susceptibility to various diseases, including cancer. We investigated the incidence of C3435T polymorphisms at exon 26 in the MDR-1 gene in 92 women with breast cancer and potential association of altered genotypes with smoking and high body mass index in cancer development among patients. The MDR-1C3435T allelotype and genotype analysis revealed a high incidence (75.0%) of polymorph alteration in the MDR-1 gene. The frequencies of homozygous T/T, heterozygous C/T and homozygous C/C genotypes were 25.0, 50.0 and 25.0%, respectively. The risk of breast carcinoma in patients with MDR-1 polymorphism was significantly associated with the higher body mass index, where women with BMI >30 kg/m2 and C allele in genotype had a higher risk of disease compared to patients with lower amounts of body fat tissue (p=0.0439). The risk was highest for the homozygous carriers of C allele with BMI >30 kg/m2 compared to patients with BMI 25.1-30 or ≤25 kg/m2 (OR 3.65, 95% CI 0.94-14.20; or OR 2.50, 95% CI 0.55-11.41), respectively. Consistent with the results of genotyping and BMI analyses, smoking patients harboring the C/T or C/C genotype had an increased risk of cancer (OR 1.28, 95% CI 0.23-7.17; OR 1.58, 95% CI 0.28-10.44, respectively) when exposed to carcinogens in tobacco smoke, although it was not statistically significant. Our findings suggest that the MDR-1C3435T polymorphism occurs in high incidence among women with breast carcinoma where C allele carriers have increased risk of developing cancer when exposed to toxic substances. Our observations are the first that indicate this polymorphism as a modulator of health to be associated with an increased risk of breast cancer.

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July 2007
Volume 18 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Zubor P, Lasabova Z, Hatok J, Stanclova A and Danko J: A polymorphism C3435T of the MDR-1 gene associated with smoking or high body mass index increases the risk of sporadic breast cancer in women. Oncol Rep 18: 211-217, 2007
APA
Zubor, P., Lasabova, Z., Hatok, J., Stanclova, A., & Danko, J. (2007). A polymorphism C3435T of the MDR-1 gene associated with smoking or high body mass index increases the risk of sporadic breast cancer in women. Oncology Reports, 18, 211-217. https://doi.org/10.3892/or.18.1.211
MLA
Zubor, P., Lasabova, Z., Hatok, J., Stanclova, A., Danko, J."A polymorphism C3435T of the MDR-1 gene associated with smoking or high body mass index increases the risk of sporadic breast cancer in women". Oncology Reports 18.1 (2007): 211-217.
Chicago
Zubor, P., Lasabova, Z., Hatok, J., Stanclova, A., Danko, J."A polymorphism C3435T of the MDR-1 gene associated with smoking or high body mass index increases the risk of sporadic breast cancer in women". Oncology Reports 18, no. 1 (2007): 211-217. https://doi.org/10.3892/or.18.1.211