AUTHOR=Ajaz Sadia , Zaidi Sani-e-Zehra , Ali Saleema Mehboob , Siddiqa Aisha , Memon Muhammad Ali , Firasat Sadaf , Abid Aiysha , Khaliq Shagufta 

TITLE=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

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.678705

DOI=10.3389/fonc.2021.678705

ISSN=2234-943X

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