Molecular evaluation of glutathione S transferase family genes in patients with sporadic colorectal cancer  

作　　者：Gabriela Helena Rodrigues-Fleming Glaucia Maria de Mendonca Fernandes Anelise Russo Patrícia Matos Biselli-Chicote Joao Gomes Netinho Erika Cristina Pavarino Eny Maria Goloni-Bertollo 

机构地区：[1]Genetics and Molecular Biology Research Unit-UPGEM,Sao Jose do Rio Preto Medical School,FAMERP,Sao Jose do Rio Preto,SP 15090-000,Brazil [2]Department of Surgery and Coloproctology,Sao Joes do Rio Preto Medical School,FAMERP,Sao Joes do Rio Preto,SP 15090-000,Brazil

出　　处：《World Journal of Gastroenterology》2018年第39期4462-4471,共10页世界胃肠病学杂志（英文版）

基　　金：Supported by the Sao Paulo Research Foundation(FAPESP),No.2011/23969-1 and No.2012/02473-0;Coordenacao de Aperfei?oamento de Pessoal de Nível Superior-Brasil(CAPES)-Finance Code 001(Master Grant);National Council of Technological and Scientific Development(CNPq)No.310582/2014-8

摘　　要：AIM To evaluate the association between polymorphismsin glutathione S transferases(GSTs) and the risk of sporadic colorectal cancer(SCRC), tumor progression and the survival of patients.METHODS A case-control study of 970 individuals from the Brazilian population was conducted(232 individuals from the case group with colorectal cancer and 738 individuals from the control group without a history of cancer). PCR multiplex and PCR-RFLP techniques were used to genotype the GST polymorphisms. The tumors were categorized according to the TNM classification: tumor extension(T), affected lymph nodes(N), and presence of metastasis(M). Logistic regression, multiple logistic regression and survival analysis were used to analyze the data. The results are presented in terms of odds ratio(OR) and 95% confidence interval(CI). The level of significance was set at 5%(P ≤ 0.05).RESULTS Age equal to or over 62 years(OR = 8.79; 95%CI: 5.90-13.09, P < 0.01) and female gender(OR = 2.91; 95%CI: 1.74-4.37; P < 0.01) were associated with increased risk of SCRC. Analysis of the polymorphisms revealed an association between the GSTM1 polymorphisms and a risk of SCRC(OR = 1.45; 95%CI: 1.06-2.00; P = 0.02), as well as between GSTT1 and a reduced risk of the disease(OR = 0.65; 95%CI: 0.43-0.98; P = 0.04). An interaction between the presence of the wild-type allele of GSTP1 Ile105 Val polymorphism and tobacco consumption on risk of SCRC(OR = 2.33; 95%CI: 1.34-4.05; P = 0.05) was observed. There was an association between the GSTM1 null genotype and the presence of advanced tumors(OR = 2.33; 95%CI: 1.23-4.41; P = 0.009), as well as increased risk of SCRC in the presence of a combination of GSTT1 non-null/GSTM1 null genotypes(OR = 1.50; 95%CI: 1.03-2.19; P = 0.03) and GSTT1 non-null/GSTM1 null/GSTP1 Val~*(OR = 1.85; 95%CI: 1.01-3.36, P = 0.04). Combined GSTT1 non-null/GSTM1 null genotypes(OR = 2.40; 95%CI: 1.19-4.85; P = 0.01) and GSTT1 non-null/GSTM1 null/GSTP1 Val~*(OR = 2.92; 95%CI: 1.05-8.12; P = 0.04) were associated with tumor progressioAIM To evaluate the association between polymorphismsin glutathione S transferases(GSTs) and the risk of sporadic colorectal cancer(SCRC), tumor progression and the survival of patients.METHODS A case-control study of 970 individuals from the Brazilian population was conducted(232 individuals from the case group with colorectal cancer and 738 individuals from the control group without a history of cancer). PCR multiplex and PCR-RFLP techniques were used to genotype the GST polymorphisms. The tumors were categorized according to the TNM classification: tumor extension(T), affected lymph nodes(N), and presence of metastasis(M). Logistic regression, multiple logistic regression and survival analysis were used to analyze the data. The results are presented in terms of odds ratio(OR) and 95% confidence interval(CI). The level of significance was set at 5%(P ≤ 0.05).RESULTS Age equal to or over 62 years(OR = 8.79; 95%CI: 5.90-13.09, P < 0.01) and female gender(OR = 2.91; 95%CI: 1.74-4.37; P < 0.01) were associated with increased risk of SCRC. Analysis of the polymorphisms revealed an association between the GSTM1 polymorphisms and a risk of SCRC(OR = 1.45; 95%CI: 1.06-2.00; P = 0.02), as well as between GSTT1 and a reduced risk of the disease(OR = 0.65; 95%CI: 0.43-0.98; P = 0.04). An interaction between the presence of the wild-type allele of GSTP1 Ile105 Val polymorphism and tobacco consumption on risk of SCRC(OR = 2.33; 95%CI: 1.34-4.05; P = 0.05) was observed. There was an association between the GSTM1 null genotype and the presence of advanced tumors(OR = 2.33; 95%CI: 1.23-4.41; P = 0.009), as well as increased risk of SCRC in the presence of a combination of GSTT1 non-null/GSTM1 null genotypes(OR = 1.50; 95%CI: 1.03-2.19; P = 0.03) and GSTT1 non-null/GSTM1 null/GSTP1 Val~*(OR = 1.85; 95%CI: 1.01-3.36, P = 0.04). Combined GSTT1 non-null/GSTM1 null genotypes(OR = 2.40; 95%CI: 1.19-4.85; P = 0.01) and GSTT1 non-null/GSTM1 null/GSTP1 Val~*(OR = 2.92; 95%CI: 1.05-8.12; P = 0.04) were associated with tumor progressio

关 键 词：Colorectal neoplasms SMOKING ALCOHOL Glutathione S transferase Genetic polymorphisms 

分 类 号：R57[医药卫生—消化系统]