O1-10-3Associations of IGFBP3 SNPs, methylation and recurrence risk in patients with stage II colorectal cancer

Background: Our previous study demonstrated that methylation of IGFBP3 was associated with recurrence of patients with stage II colorectal cancer (CRC). In this study, we aim to evaluate the possible correlation between single nucleotide polymorphisms (SNPs) and methylation of IGFBP3, and the influence of SNPs on recurrence.Methods: Nine SNPs at IGFBP3 of DNA from 115 primary tumors of patients with stage II CRC were analyzed. Forty patients developed recurrence, whereas matched 75 patients remained recurrence-free for more than 2 years after surgery. Logistic regression was applied to detect odds ratios (ORs) and 95% confidence intervals (CIs) for the correlation between SNPs and DNA methylation. In multivariate analyses, hazard ratios (HRs) were adjusted for age, sex, tumor location and differentiation. Cox proportional hazards models were used to calculate HRs of recurrence, adjusted for patient and tumor characteristics.Results: We included 115 patients and successfully genotyped 9 SNPs in this cohort. The polymorphism rs2132572 was significantly correlated with hypermethylation, OR = 3.50 (95% CI, 1.07 to 11.44; P = 0.038) in univariate analysis and OR = 3.65 (95% CI, 1.05 to 12.71; P = 0.042) in multivariate analysis. The polymorphism rs3110697 was identified to be significantly associated with risk of recurrence. Patients with one or two copies of the minor (risk) allele had an increased risk of recurrence. Five-year recurrence-free survival rates were 59.2% and 85.8% for patients without the risk allele and carriers of the risk allele, respectively, HR = 3.85 (95% CI, 1.37 to 10.85; P = 0.011). In multivariate analysis, the signature remained significant, with a HR of 3.13 (95% CI, 1.06 to 9.24; P = 0.039).Conclusion: We have found an association between the polymorphism rs2132572 and methylation of IGFBP3 in CRC. Patients with the IGFBP3 polymorphism rs3110697 might have an increased risk of recurrence after radical surgery for stage II CRC. Background: Our previous study demonstrated that methylation of IGFBP3 was associated with recurrence of patients with stage II colorectal cancer (CRC). In this study, we aim to evaluate the possible correlation between single nucleotide polymorphisms (SNPs) and methylation of IGFBP3, and the influence of SNPs on recurrence. Methods: Nine SNPs at IGFBP3 of DNA from 115 primary tumors of patients with stage II CRC were analyzed. Forty patients developed recurrence, whereas matched 75 patients remained recurrence-free for more than 2 years after surgery. Logistic regression was applied to detect odds ratios (ORs) and 95% confidence intervals (CIs) for the correlation between SNPs and DNA methylation. In multivariate analyses, hazard ratios (HRs) were adjusted for age, sex, tumor location and differentiation. Cox proportional hazards models were used to calculate HRs of recurrence, adjusted for patient and tumor characteristics. Results: We included 115 patients and successfully genotyped 9 SNPs in this cohort. The polymorphism rs2132572 was significantly correlated with hypermethylation, OR = 3.50 (95% CI, 1.07 to 11.44; P = 0.038) in univariate analysis and OR = 3.65 (95% CI, 1.05 to 12.71; P = 0.042) in multivariate analysis. The polymorphism rs3110697 was identified to be significantly associated with risk of recurrence. Patients with one or two copies of the minor (risk) allele had an increased risk of recurrence. Five-year recurrence-free survival rates were 59.2% and 85.8% for patients without the risk allele and carriers of the risk allele, respectively, HR = 3.85 (95% CI, 1.37 to 10.85; P = 0.011). In multivariate analysis, the signature remained significant, with a HR of 3.13 (95% CI, 1.06 to 9.24; P = 0.039). Conclusion: We have found an association between the polymorphism rs2132572 and methylation of IGFBP3 in CRC. Patients with the IGFBP3 polymorphism rs3110697 might have an increased risk of recurrence after radical surgery for stage II CRC.