title: Association of common gene variants in vitamin D modulating genes and colon cancer recurrence.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Clinical Oncology, Department of Medicine, Medical University of Graz, Graz, Austria.
authors.forename: Joanna
authors.initials: J
authors.lastname: Szkandera
authors.forename: Gudrun
authors.initials: G
authors.lastname: Absenger
authors.forename: Martin
authors.initials: M
authors.lastname: Pichler
authors.forename: Michael
authors.initials: M
authors.lastname: Stotz
authors.forename: Tanja
authors.initials: T
authors.lastname: Langsenlehner
authors.forename: Hellmut
authors.initials: H
authors.lastname: Samonigg
authors.forename: Wilfried
authors.initials: W
authors.lastname: Renner
authors.forename: Armin
authors.initials: A
authors.lastname: Gerger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D000072467:Cytochrome P450 Family 2; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D009367:Neoplasm Staging; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012189:Retrospective Studies; D013997:Time Factors; D014759:Viral Envelope Proteins / Q000235:genetics*; D014807:Vitamin D / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D014759:Viral Envelope Proteins; C038535:glycoprotein gC, herpes simplex virus type 1; D014807:Vitamin D; D000072467:Cytochrome P450 Family 2; C506833:CYP2R1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019995:7-dehydrocholesterol reductase