Association Beteen SNPs Of ABH And Lewis Histo-Blood Group Genes And Preoperative Serum CEA Levels In Colorectal Cancer Patients And Its Clinical Implications

Background&Objective Colorectal carcinoma(CRC) is one of the most common malignancies with increasing incidence in the world. Carcinoembryonic antigen (CEA) is one of the most widely used tumor marker to diagnose and monitor recurrence for Colorectal carcinoma. ABH and lewis histo-blood group antigens are widely distributed in human tissues. A genome-wide association study (GWAS) organized by Mo et al have found that some single nucleotide polymorphism (SNP) loci of ABH and Lewis histo-blood group system gene are related to the level of serum CEA.The purpose of this study is to (1)explore the distribution frequency and characteristics of5SNPs loci (rs8176746、rs687289、rs1047781、 rs3760775、rs2071699、) in ABH and Lewis histo-blood group system gene in CRC patients,(2)determine the relationship between genotypes of this5SNPs and preoperative CEA level and clinical pathological features of CRC.(3) analyze the relationship between genotypes of these5SNPs and the prognosis of CRC patients.Methods190patients with colorectal carcinoma who underwent surgical resection at the department of colorectal and anal surgery in The First Affiliated Hospital of Guangxi Medical University from February2008to January2010were included in this study. Genomic DNA was isolated using the TIANamp Genomic DNA Kit from normal colorectal mucosa tissue. Three millilitres of venous blood was obtained from each patient1week before operation. CEA in serum (S-CEA) measurements were done by the department of clinical laboratory in our hospital using Cobas e601analyzer system (Roche Diagnostics GmbH, Mannheim, Germany). The genotype of5common SNP loci in ABH and Lewis histo-blood group system gene were measured with TaqMan MGB, a real-time fluorescence quantitative PCR method。173patients with stage Ⅰ-Ⅲ were followed until January31,2012. Disease free survival was determined from the time interval between the primary surgery with curative intent until the diagnosis of recurrent or death. All data were analyzed statistically in SPSS16.0for windows. Continuous data were analyzed using thenonparametric Mann-Whitney U test or Kruskal-Wallis H test. Categorical data were analyzed using chi-square test or Fisher’s exact test. Kaplan-Meier method was used to calculate survival rate and draw survival curves, and log-rank test was used to determine univariate significance.factor that were deemed of potential importance on univariate analysis were introduced into COX regression model for multivariate survival analysis by conditional forward method. All tests were two-tailed and significance was set at p<0.05.Results The results of this study confirm that the two SNP loci rs8176746and rs687289are related with ABO blood group.The genotype of rs1047781loci which located in FUT2gene is associated with the preoperative CEA leve of the patients with colorectal cancer. The preoperative CEA leve of CRC is associated with age and pathological staging. There was positive correlation between the preoperative CEA and TNM staging.(P<0.05). Preoperative CEA level and pathological staging are significantly asociated with DFS of colorectal cancer. All five SNPs loci which we have analyzed have no significant correlation with DFS of colorectal cancer.Conclusion The polymorphism of rs8176746and rs687289are related with ABO blood group. The genotype of rs1047781is associated with the preoperative CEA leve of CRC patients.The preoperative CEA leve of CRC is associated with age and pathological staging. Preoperative CEA level and pathological staging are significantly associated with DFS of CRC.