Assessment of Serum Glutathione S-Transferase Gene Polymorphisms in Iraqi Patients Diagnosed with Colorectal Cancer

Abstract

ABSTRACT— Colorectal cancer is a prevalent disease that originates with abnormal proliferation of the inner colon or rectum, expanding through the whole thickness of the epithelial lining, then disseminating to adjacent lymph nodes and organs, and ultimately leading to distant metastases. It ranks as one of the most complicated cancers to cure, associated with complex interactions between environmental factors and genetic susceptibility, with severe symptoms that exacerbate and become more precise and particular as the illness advances, resulting in an elevated rate of mortality and short lifespan if diagnosed late or untreated. Molecular analysis reveals that glutathione S-transferase (GST) is a crucial detoxifying enzyme involved in cellular defense against oxidative stress. Polymorphisms of GST Mu1 (M1) and Theta1 (T1) genes may affect enzymes' capacity to metabolize chemical carcinogens and mutagens and their combined impact on CRC risk.

Methods: A case-control study evaluated the frequency of GSTM1 and GSTT1 null genotypes in CRC patients compared with healthy individuals. The participants of the study were 58 cases, consisting of both healthy individuals and patients, divided into two categories: The first had 38 patients. The second group had 20 healthy individuals. DNA was isolated from whole blood, and genotyping was performed using a conventional Polymerase Chain Reaction assay.

Results: The current study showed that the frequency of the GSTM1 and GSTT1null genotypes was 52.63% and 15.79%, respectively, revealing a highly significant difference (P=0.001) between GSTM1 and GSTT1 genotypes and a significant difference (P=0.041) between GSTT1 and the control group. Furthermore, stratified analysis indicated that the GSTM1 null genotype was significantly associated with smoking habit (P=0.024) and family history (P<0.001), while the GSTT1 null genotype was associated with early-onset cancer in patients aged <50 years (P=0.021).

In conclusion, our research indicates that the Iraqi population's vulnerability to colorectal cancer may be linked to variations in the GSTT1 gene.