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

Sadia Ajaz; Sani-E-Zehra Zaidi; Saleema Mehboob Ali; Aisha Siddiqa; Muhammad Ali Memon; Sadaf Firasat; Aiysha Abid; Shagufta Khaliq

doi:10.3389/fonc.2021.678705

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

Front Oncol. 2021 Dec 6:11:678705. doi: 10.3389/fonc.2021.678705. eCollection 2021.

Authors

Sadia Ajaz^{1

2}, Sani-E-Zehra Zaidi¹, Saleema Mehboob Ali¹, Aisha Siddiqa³, Muhammad Ali Memon³, Sadaf Firasat⁴, Aiysha Abid³, Shagufta Khaliq²

Affiliations

¹ Dr Panjwani Center for Molecular Medicine and Drug Research (PCMD), International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi, Pakistan.
² Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore, Pakistan.
³ Atomic Energy Medical Centre (AEMC), Jinnah Postgraduate Medical Centre (JPMC), Karachi, Pakistan.
⁴ Centre for Human Genetics and Molecular Medicine, Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan.

Abstract

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 genotyping 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.

Keywords: GSTT1-absent; GSTT1-present; breast cancer; molecular epidemiology; null genotype; polymorphism.