Deletion of Glutathione S-Transferase Theta 1 (GSTT1) encoding gene is implicated in breast cancer susceptibility, clinical outcomes, and survival. Contradictory results have been reported in different studies. The present investigation based on a representative Pakistani population evaluated the -absent genotype in breast cancer risk and prognosis.
A prospective study comprising case-control analysis and case series analysis components was designed. Peripheral blood samples were collected from enrolled participants. After DNA extraction, enotyping was carried out by a multiplex PCR with as an amplification control. Association evaluation of genotypes with breast cancer risk, specific tumor characteristics, and survival were the primary endpoints.
A total of 264 participants were enrolled in the molecular investigation (3 institutions). The study included 121 primary breast cancer patients as cases and 143 age-matched female subjects, with no history of any cancer, as controls. A significant genetic association between -absent genotype and breast cancer susceptibility (-value: 0.03; OR: 2.13; 95% CI: 1.08-4.29) was reported. The case-series analysis showed lack of association of genotypes with menopause (value: 0.86), tumor stage (-value: 0.12), grade (-value: 0.32), and size (-value: 0.07). The survival analysis revealed that -absent genotype cases had a statistically significant shorter overall survival (OS) than those with the -present genotype cases (mean OS: 23 months 33 months). The HR (95% CI) for OS in patients carrying -absent genotype was 8.13 (2.91-22.96) when compared with the -present genotype.
The present study is the first report of an independent significant genetic association between -absent genotype and breast cancer susceptibility in a Pakistani population. It is also the foremost report of the association of this genotype with OS in breast cancer cases. Upon further validation, variation may serve as a marker for devising better population-specific strategies. The information may have translational implications in the screening and treatment of breast cancers.
Copyright © 2021 Ajaz, Zaidi, Ali, Siddiqa, Memon, Firasat, Abid and Khaliq.
Absence of Gene Is Significantly Associated With Breast Cancer Susceptibility in Pakistani Population and Poor Overall Survival in Breast Cancer Patients: A Case-Control and Case Series Analysis.
