RESUMO
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.
Assuntos
Colestanotriol 26-Mono-Oxigenase/genética , Neoplasias do Colo/genética , Recidiva Local de Neoplasia/diagnóstico , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas do Envelope Viral/genética , Vitamina D/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Neoplasias do Colo/patologia , Neoplasias do Colo/terapia , Família 2 do Citocromo P450 , DNA de Neoplasias/genética , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Prognóstico , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: Integrins influence tumourigenesis, tumor progression and development of metastases. The impact of polymorphisms in integrin genes on relapse-free survival (RFS) and overall survival (OS) for 433 Caucasian patients with colorectal cancer was analysed in this retrospective study. PATIENTS AND METHODS: A Cox regression model including integrin genotype, age, grading, tumour size, number of lymph nodes examined, number of metastatic lymph nodes, stage and application of fluorouracil-based adjuvant chemotherapy was used to estimate their effect. RESULTS: After a median follow-up of 41 months for RFS and 55 months for OS, no significant correlation between the ITGA2 1648A allele (RFS p=0.618, OS p=0.604), the ITGA2 807T allele (RFS p=0.603, OS p=0.807) and the ITGB3 176C allele (RFS p=0.719, OS p=0.261) and survival was detectable. CONCLUSION: The investigated integrin polymorphisms are not associated with RFS or OS in colorectal cancer patients.