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

Author(s)

Rodrigues-Fleming, Gabriela Helena ^[1] ; de Mendonca Fernandes, Glaucia Maria ^[1] ; Russo, Anelise ^[1] ; Biselli-Chicote, Patricia Matos ^[1] ; Netinho, Joao Gomes ^[2] ; Pavarino, Erika Cristina ^[1] ; Goloni-Bertollo, Eny Maria ^[1]

Affiliation

^[1] FAMERP, Sao Jose do Rio Preto Med Sch, Genet & Mol Biol Res Unit UPGEM, BR-15090000 Sao Jose Do Rio Preto, SP - Brazil

^[2] FAMERP, Sao Jose do Rio Preto Med Sch, Dept Surg & Coloproctol, BR-15090000 Sao Jose Do Rio Preto, SP - Brazil

• Document type: Journal article
• Source: WORLD JOURNAL OF GASTROENTEROLOGY; v. 24, n. 39, p. 4462-4471, OCT 21 2018.
• Web of Science Citations: 0

Abstract

AIM To evaluate the association between polymorphisms in 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 Ile105Val 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 progression. Polymorphisms were not associated with the survival of patients with SCRC. CONCLUSION Females aged 62 years or older are more susceptible to SCRC. Polymorphisms of GSTT1 and GSTM1 null genotypes modulated the susceptibility to SCRC in the population studied. (AU)

• FAPESP's process: 12/02473-0 - Epidemiological and molecular investigation of genes related to xenobiotic metabolism in patients with sporadic colerrectal cancer
• Grantee: Glaucia Maria de Mendonça Fernandes
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 11/23969-1 - Epidemiological and molecular investigation of genes related to xenobiotic metabolism in patients with sporadic colerrectal cancer
• Grantee: Eny Maria Goloni Bertollo
• Support Opportunities: Regular Research Grants