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Association of common gene variants in vitamin D modulating genes and colon cancer recurrence

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Abstract

Purpose

Low concentrations of 25-hydroxyvitamin D3 (25(OH)D) have been associated with increased risk and poor prognosis of various cancer types, including colon cancer. Common genetic variants in genes that influence circulating 25(OH)D levels may affect vitamin D concentrations and risk of vitamin D insufficiency. In the present study, we investigated the association of three functional gene variants in GC (rs2282679 T>G), DHCR7 (rs12785878 G>T) and CYP2R1 (rs10741657 A>G) with time to recurrence (TTR) in patients with stages II and III colon cancer.

Methods

Two hundred and sixty-four patients were included in this retrospective study. Genomic DNA was genotyped for GC rs2282679 T>G, DHCR7 rs12785878 G>T and CYP2R1 rs10741657 A>G by 5′-exonuclease (TaqMan™) technology.

Results

In the univariate analysis, GC rs2282679 GG was significantly associated with decreased TTR (HR = 3.30, 95 % CI 1.09–9.97, p = 0.034) in patients with surgery alone and remained significantly associated in multivariate analysis including lymph node involvement and clinical stage (HR = 3.64, 95 % CI 1.16–11.46, p = 0.027). In patients with adjuvant chemotherapy, GC rs2282679 T>G was not significantly associated with TTR (HR = 1.02, 95 % CI 0.44–2.37, p = 0.964). Furthermore, we observed a trend toward decreased TTR in patients harboring the CYP2R1 rs10741657 A>G gene variant including all patients (HR = 1.50, 95 % CI 0.98–2.28, p = 0.060). No association was found between DHCR7 rs12785878 G>T and TTR in our study cohort.

Conclusion

In conclusion, our results may indicate a prognostic effect of GC rs2282679 in stages II and III colon cancer patients with surgery alone. Larger studies have to be performed to validate our findings.

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Acknowledgments

This work was supported by the City Graz Science Foundation.

Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Division of Clinical Oncology, Department of Medicine, Medical University of Graz, Graz, Austria

    Joanna Szkandera, Gudrun Absenger, Martin Pichler, Michael Stotz, Hellmut Samonigg & Armin Gerger

  2. Research Unit, Genetic Epidemiology and Pharmacogenetics, Division of Clinical Oncology, Department of Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria

    Joanna Szkandera, Gudrun Absenger, Wilfried Renner & Armin Gerger

  3. Department of Therapeutic Radiology and Oncology, Medical University of Graz, Graz, Austria

    Tanja Langsenlehner

  4. Clinical Institute of Medical and Laboratory Diagnostics, Medical University of Graz, Graz, Austria

    Wilfried Renner

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  1. Joanna Szkandera
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Correspondence to Armin Gerger.

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Szkandera, J., Absenger, G., Pichler, M. et al. Association of common gene variants in vitamin D modulating genes and colon cancer recurrence. J Cancer Res Clin Oncol 139, 1457–1464 (2013). https://doi.org/10.1007/s00432-013-1461-x

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