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Purpose  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  GSTT1 -absent genotype in breast cancer risk and prognosis.    Methods  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,  GSTT1 g enotyping was carried out by a multiplex PCR with  β-globin  as an amplification control. Association evaluation of  GSTT1  genotypes with breast cancer risk, specific tumor characteristics, and survival were the primary endpoints.    Results  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  GSTT1 -absent genotype and breast cancer susceptibility ( p -value: 0.03; OR: 2.13; 95% CI: 1.08-4.29) was reported. The case-series analysis showed lack of association of  GSTT1  genotypes with menopause ( p- value: 0.86), tumor stage ( p -value: 0.12), grade ( p -value: 0.32), and size ( p -value: 0.07). The survival analysis revealed that  GSTT1 -absent genotype cases had a statistically significant shorter overall survival (OS) than those with the  GSTT1 -present genotype cases (mean OS: 23 months  vs  33 months). The HR (95% CI) for OS in patients carrying  GSTT1 -absent genotype was 8.13 (2.91-22.96) when compared with the  GSTT1 -present genotype.    Conclusions  The present study is the first report of an independent significant genetic association between  GSTT1 -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,  GSTT1  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.

frontiers in oncology

Absence of Glutathione S-Transferase Theta 1 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