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

Abstract

AIMTo 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.METHODSA 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).RESULTSAge 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.CONCLUSIONFemales 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.

Glutathione S-transferase Polymorphisms in Head and Neck Squamous Cell Carcinoma Treated with Chemotherapy and/or Radiotherapy

“…The present study confirmed data from the literature, that report the predominance of cases between the fourth and sixth decade of life, and that smoking and alcohol consumption is strongly related to increased risk of developing this type of cancer (Choudhury et al, 2015;Rodrigues-Fleming et al, 2018). The studies carried out in Northeastern Brazil evidenced increased risk of oral cancer in patients presenting smoking and alcohol consumption synergism compared to non-synergetic consumption of cigarettes and alcohol (Andrade et al, 2015;Dias et al, 2017).…”

Individual and combined effects of GSTM1 and GSTT1 polymorphisms on colorectal cancer risk: an updated meta-analysis

“…Sixty-three articles of sixy-four case–control studies [ 15–17 , 19 , 21–24 , 26 , 27 , 30 , 31 , 33 , 34 , 36 , 38–42 , 45 , 47 , 48–52 , 54–58 , 62–64 , 67–70 , 73 , 74 , 76–78 , 80–82 , 87–90 , 93 , 96–99 , 102 , 105 , 109 , 111–114 ] were eligible concerning the GSTT1 present/null polymorphism (19,725 cases and 28,725 controls; 34 studies on Caucasians, 23 on Asians, one on Indians, one on Africans, and five on mixed populations) with CRC risk. Thirty-two publications of thirty-three case–control studies [ 15 , 19 , 22–24 , 27 , 31 , 33 , 38 , 39 , 41 , 42 , 45 , 49 , 52 , 55–57 , 63 , 67 , 68 , 70 , 76–78 , 90 , 96 , 97 , 99 , 105 , 109 , 112 ] were included regarding their combined effects (8270 cases and 14,381 controls; 11 studies on Caucasians, 17 on Asians, one on Indians, one on Africans, and three on mixed populations) with CRC risk. Fifty-five studies had a quality score ≥ 6 and the remaining 31 had a quality score < 6 regarding the GSTM1 present/null polymorphism; 48 high-quality studies were examined and the remaining 16 were low-quality concerning the GSTT1 present/null polymorphism; a total of 25 high-quality and eight low-quality studies were included on their combined effects with CRC risk.…”

GST gene family polymorphism and the risk of colorectal cancer in patients with type 2 diabetes

“…According to research, the polymorphism of GST genes may influence the risk of developing T2D, as well as its course, complications and treatment effectiveness [9,10]. Similar observations were made for CDC, where the GST genotype may be a factor modifying the risk of disease development and progression [7,11,12].…”