Open Access

Two common polymorphic variants of OATP4A1 as potential risk factors for colorectal cancer

  • Authors:
    • Veronika Buxhofer‑Ausch
    • Orsolya Német
    • Majdah Sheikh
    • Hajnalka Andrikovics
    • Angelika Reiner
    • Christoph Ausch
    • Diana Mechtcheriakova
    • Attila Tordai
    • Andreas Gleiss
    • Csilla Özvegy‑laczka
    • Walter Jäger
    • Theresia Thalhammer
  • View Affiliations

  • Published online on: September 17, 2020     https://doi.org/10.3892/ol.2020.12115
  • Article Number: 252
  • Copyright: © Buxhofer‑Ausch et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Genetic variations in the organic‑anion‑transporting polypeptide (OATP)‑encoding solute carrier of organic anions (SLCO) genes can promote cancer development and progression. The overexpression of solute carrier organic anion transporter family member 4A1 (OATP4A1), a transporter for steroid hormones, prostaglandins, and bile acids, has been previously associated with tumor recurrence and progression in colorectal cancer (CRC). Therefore, the present study aimed to investigate the association between 2 frequent single nucleotide polymorphisms (SNPs) in SLCO4A1 (rs34419428, R70Q; rs1047099G, V78I) and CRC predisposition. Following restriction fragment length polymorphism‑PCR analysis in 178 patients with CRC [Union for International Cancer Control (UICC) stage I/II] and 65 healthy controls, no significant difference was observed in allele frequency and the number of heterozygous/homozygous individuals between the groups. Notably, the R70Q minor allele was identified to be associated with the V78I minor allele in the genome. Comparing of the individual genotypes of CRC patients to clinical data, including sex, UICC‑stage and relapse revealed no increased risk for CRC. In addition, the OATP4A1 immunoreactivity assay in paraffin‑embedded CRC and adjacent non‑tumorous mucosa sections, examined using quantitative microscopy image analysis, did not reveal any association with these polymorphisms. No significant differences were observed in the expression levels, localization, and sodium fluorescein transport capacity among the OATP4A1 variants, which was studied using functional assays in Sf9‑insect and A431 tumor cells overexpressing the 2 single and a double mutant OATP4A1 SNP variants. These results suggested that the 2 most frequent polymorphisms located in the first intracellular loop of OATP4A1 do not associate with CRC predisposition and tumor recurrence. They are unlikely to affect the outcome of CRC in patients.
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November-2020
Volume 20 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Buxhofer‑Ausch V, Német O, Sheikh M, Andrikovics H, Reiner A, Ausch C, Mechtcheriakova D, Tordai A, Gleiss A, Özvegy‑laczka C, Özvegy‑laczka C, et al: Two common polymorphic variants of OATP4A1 as potential risk factors for colorectal cancer. Oncol Lett 20: 252, 2020.
APA
Buxhofer‑Ausch, V., Német, O., Sheikh, M., Andrikovics, H., Reiner, A., Ausch, C. ... Thalhammer, T. (2020). Two common polymorphic variants of OATP4A1 as potential risk factors for colorectal cancer. Oncology Letters, 20, 252. https://doi.org/10.3892/ol.2020.12115
MLA
Buxhofer‑Ausch, V., Német, O., Sheikh, M., Andrikovics, H., Reiner, A., Ausch, C., Mechtcheriakova, D., Tordai, A., Gleiss, A., Özvegy‑laczka, C., Jäger, W., Thalhammer, T."Two common polymorphic variants of OATP4A1 as potential risk factors for colorectal cancer". Oncology Letters 20.5 (2020): 252.
Chicago
Buxhofer‑Ausch, V., Német, O., Sheikh, M., Andrikovics, H., Reiner, A., Ausch, C., Mechtcheriakova, D., Tordai, A., Gleiss, A., Özvegy‑laczka, C., Jäger, W., Thalhammer, T."Two common polymorphic variants of OATP4A1 as potential risk factors for colorectal cancer". Oncology Letters 20, no. 5 (2020): 252. https://doi.org/10.3892/ol.2020.12115