Ajaz Sadia, Zaidi Sani-E-Zehra, Ali Saleema Mehboob, Siddiqa Aisha, Memon Muhammad Ali, Firasat Sadaf, Abid Aiysha, Khaliq Shagufta
Dr Panjwani Center for Molecular Medicine and Drug Research (PCMD), International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi, Pakistan.
Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore, Pakistan.
Front Oncol. 2021 Dec 6;11:678705. doi: 10.3389/fonc.2021.678705. eCollection 2021.
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.
谷胱甘肽S-转移酶θ1（GSTT1）编码基因的缺失与乳腺癌易感性、临床结局及生存率有关。不同研究报告的结果相互矛盾。本研究基于具有代表性的巴基斯坦人群，评估了该基因缺失基因型与乳腺癌风险及预后的关系。
设计了一项前瞻性研究，包括病例对照分析和病例系列分析。收集入组参与者的外周血样本。DNA提取后，采用多重PCR进行基因分型，并以某物质作为扩增对照。该基因不同基因型与乳腺癌风险、特定肿瘤特征及生存率的关联评估为主要研究终点。
共有264名参与者纳入分子研究（3家机构）。该研究纳入121例原发性乳腺癌患者作为病例组，143名年龄匹配、无任何癌症病史的女性作为对照组。报告显示该基因缺失基因型与乳腺癌易感性之间存在显著的遗传关联（P值：0.03；OR：2.13；95%CI：1.08 - 4.29）。病例系列分析表明该基因不同基因型与绝经状态（P值：0.86）、肿瘤分期（P值：0.12）、分级（P值：0.32）及大小（P值：0.07）均无关联。生存分析显示，该基因缺失基因型的病例总体生存率（OS）在统计学上显著低于该基因存在基因型的病例（平均OS：23个月对33个月）。与该基因存在基因型相比，携带该基因缺失基因型患者的OS的HR（95%CI）为8.13（2.91 - 22.96）。
本研究首次报道了在巴基斯坦人群中该基因缺失基因型与乳腺癌易感性之间存在独立的显著遗传关联。这也是该基因型与乳腺癌病例OS关联的首份重要报告。经进一步验证后，该基因变异可能成为制定更优的人群特异性策略的标志物。该信息可能对乳腺癌的筛查和治疗具有转化意义。
