Association of common gene variants in vitamin D modulating genes and colon cancer recurrence
- PMID: 23793229
- PMCID: PMC11824294
- DOI: 10.1007/s00432-013-1461-x
Association of common gene variants in vitamin D modulating genes and colon cancer recurrence
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.
Conflict of interest statement
We declare that we have no conflict of interest.
Figures
References
-
- Ahn J, Yu K, Stolzenberg-Solomon R, Simon KC, McCullough ML, Gallicchio L, Jacobs EJ, Ascherio A, Helzlsouer K, Jacobs KB, Li Q, Weinstein SJ, Purdue M, Virtamo J, Horst R, Wheeler W, Chanock S, Hunter DJ, Hayes RB, Kraft P, Albanes D (2010) Genome-wide association study of circulating vitamin D levels. Hum Mol Genet 19(13):2739–2745. doi:10.1093/hmg/ddq155 - PMC - PubMed
-
- Ahonen MH, Tenkanen L, Teppo L, Hakama M, Tuohimaa P (2000) Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland). Cancer Causes Control 11(9):847–852 - PubMed
-
- Bareis P, Bises G, Bischof MG, Cross HS, Peterlik M (2001) 25-hydroxy-vitamin D metabolism in human colon cancer cells during tumor progression. Biochem Biophys Res Commun 285(4):1012–1017 - PubMed
-
- Ben-Shoshan M, Amir S, Dang DT, Dang LH, Weisman Y, Mabjeesh NJ (2007) 1alpha,25-dihydroxyvitamin D3 (Calcitriol) inhibits hypoxia-inducible factor-1/vascular endothelial growth factor pathway in human cancer cells. Mol Cancer Ther 6(4):1433–1439. doi:10.1158/1535-7163.MCT-06-0677 - PubMed
-
- Bises G, Kállay E, Weiland T, Wrba F, Wenzl E, Bonner E, Kriwanek S, Obrist P, Cross HS (2004) 25-hydroxyvitamin D3–1alpha-hydroxylase expression in normal and malignant human colon. J Histochem Cytochem 52(7):985–989. doi:10.1369/jhc.4B6271.2004 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous
