Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) genetic polymorphism and susceptibility to gastric and colorectal adenocarcinoma

Abstract

Genes coding for the glutathione S-transferase M1 (GSTM1) and Theta 1 (GSTT1) proteins are polymorphic in humans and these genes are absent, or homozygous null, in 10-60% of different ethnic populations. These enzymes catalyze the conjugation of glutathione to numerous carcinogenic chemicals and previous epidemiologic studies have associated the null genotypes of these GST genes with higher risk of cancer. In this study the frequency of GSTM1 and GSTT1 null genotypes was determined in Japanese patients with gastric adenocarcinoma and colorectal adenocarcinoma and compared to frequencies determined in a community-based control group. The frequency of the null GSTM1 genotype in patients with gastric adenocarcinoma (56.8%) showed a statistically significant increase compared to the control group frequency (43.6%) (odds ratio (OR) = 1.70; 95% CI, 1.05-2.76). The frequency of GSTM1 null individuals was also higher among all colorectal adenocarcinoma cases, but this increase did not reach statistical significance. After grouping by tumor site, the GSTM1 null genotype was a risk factor among the subgroup with distal colorectal tumors (61.1%) (OR = 2.03; 95% CI, 1.06-3.90). No consistent difference was observed between smoking patients and corresponding controls for the frequency of the GSTM1 null genotype for either cancer, although a large risk (OR = 5.76; 95% CI 1.18-28.3) was associated with the GSTM1 null genotype in the low smoking group of gastric adenocarcinoma patients. On the other hand, no statistically significant differences were observed in the frequency of null GSTT1 genotypes in gastric (47.5%) or colorectal (48.5%) adenocarcinoma patients when compared with the control population (44.4%). These results suggest that the GSTM1 null genotype may be associated with susceptibility to gastric adenocarcinoma and distal colorectal adenocarcinoma in Japanese; however, the associations observed were relatively weak and additional studies will be needed to confirm these findings.

Increased risk for treatment-related mortality after bone marrow transplantation in GSTM1-positive recipients

“…A homozygous deletion of the GSTM1 and GSTT1 genes was found in B57 and B46% of healthy donors, respectively, which was comparable to the previous Japanese studies. 7,16 Of patients with a hematological malignancy, homozygous deletion of the GSTM1 and GSTT1 genes was found in B56 and B45%, respectively, and there was no difference in the frequencies between each disease group and donor group. The findings, of no association between both GSTM1-and GSTT1-null genotypes and risk of each hematological malignancy, were consistent with our previous study in a different Japanese population; 7 however, many studies have emphasized the importance of these genetic polymorphisms in susceptibility to hematological diseases.…”

Evaluation of Insulin Like Growth Facror-1 Genetic Polymorphism with Gastric Cancer Susceptibility and Clinicopathological Features

“…The etiology of GC is not clearly known. Several risk factors include environmental agents (diet, smoking); infectious aspects (Helicobacter pylori) and genetic factors are suspected to play a significant role in gastric carcinogenesis (Katoh et al, 1996;Stadtlander 1999;Setiawan et al, 2000;Forman and Burley, 2006;Rostami et al, 2011). Among the some genetic changes, there is evidence that the upregulation of certain growth factors could play a significant role in the development and progression of gastric cancer .…”

Polymorphism of the glutathione transferase subunit 3 in Sprague–Dawley rats involves a reactive cysteine residue

“…Loss of these genes has been suggested as a possible marker for greater susceptibility to development of lung cancer, as well as other cancers [19,20]. However, whether such polymorphisms also exist in the rat has remained unclear.…”