ISSN : 2663-2187

Glutathione -S-transferase gene polymorphism (GSTT1 and GSTM1) and Cytochrome P450 (CYP2D6) polymorphism and breast cancer susceptibility in Egyptian women

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Safaa . A.Barakat , Abdel-Hamed Ismail, Afaf El-Said, Hayam F. Ghazy, Magdy M. Youssef
» doi: 10.48047/AFJBS.6.15.2024.9777-9800

Abstract

Background: The enzymes GSTM1, GSTT1, GSTP1, CYP1A1, and CYP2E1 promote the bio activation and detoxification of many xenobiotics that can be found in food, organic solvents, tobacco smoke, medications, pesticides, environmental pollutants, and alcoholic beverages. The genes that encode these enzymes have variations that have been associated with certain indicators of sickness vulnerability. Aim: This study seeks to understand whether there is a correlation between breast cancer risk in Egyptian women and variations in Glutathione-S-transferase and CYP2D6. Methodology: Out of 202 participants in the case-control study, 46.0% had the GSTT1 (0) /GSTM1 (0) genotype. A tumor-node-metastasis staging approach, adapted from the International Union Against Cancer and the American Joint Committee on Cancer, was used to compare breast cancer patients with and without the disease. Using immune histochemistry approaches, prognostic indicators such as HER2/neu and ER/PR were found. Comprehensive blood counts (CBCs), cancer antigen 15-3 and carcinoembryonic antigen (CEA), albumin, bilirubin, albumin-lowering plasma protein (ALP), creatinine, and uric acid were assessed. Results: The study indicated that the frequencies of GSTT0/GSTM0 were considerably higher in breast cancer cases (43% vs. 49.5% in healthy controls). Cases (54.5%) had a higher frequency of the '*2' allele compared to controls (9.5%). Case and control groups also differed significantly in genetic distribution. Cases had a larger proportion of the Wt/Wt genotype, whereas controls had higher proportions of the Wt/*2 and *2/*2 genotypes. A crude odds ratio of 4.1 indicates that the prevalence of GSTT1/0 was higher in cases (75.2%) compared to controls (42.6%). There was a little increase in GSTM1 in cases (55.4% vs. 49.5% in controls). When comparing controls and cases, the former had more GSTT1 with or without GSTM1 and the latter had more GSTT1 without or with GSTM1. Conclusion: The results showed that among Egyptian women, GSTM1/0 mutations had a 4.1 fold increased risk of breast cancer. Breast cancer risk is elevated in people with CYP2D6 *2 alleles. When these genotypes are coupled with characteristics related to lifestyle or the environment, the risk can be amplified.

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