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

PurposeDeletion 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.MethodsA 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.ResultsA 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.ConclusionsThe 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.

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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

10.1101/2021.02.18.21252044 ◽

2021 ◽

Author(s):

Sadia Ajaz ◽

Sani-e-Zehra Zaidi ◽

Saleema Mehboob Ali ◽

Aisha Siddiqa ◽

Muhammad Ali Memon ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Breast Cancer Risk ◽

Cancer Susceptibility ◽

Case Series ◽

Breast Cancer Susceptibility ◽

Case Control ◽

Breast Cancer Patients ◽

Pakistani Population ◽

Series Analysis

AbstractPurposeDeletion 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 evaluated GSTT1-absent genotype for its’ contribution to breast cancer risk in Pakistani population and specific clinical outcomes in breast tumours.MethodsA 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 tumour characteristics, and survival was the primary endpoint.ResultsA 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 subject, with no history of any cancer, as controls. A significant genetic association between GSTT1-absent genotype and breast cancer susceptibility (p-value: 0.003; OR: 2.13; 95% CI: 1.08-4.29) is reported. The case-series analysis showed lack of association of GSTT1 genotypes with tumour 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 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 GSTT1-present genotype.ConclusionsThe present study is the first report of an independent, population-oriented significant genetic association between GSTT1-absent genotype and breast cancer susceptibility as well as OS in breast cancer cases. Upon further validation, GSTT1 variation may serve as a marker for devising better and population-specific strategies for screening and treatment in breast cancer management.

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LncRNA MEG3 rs3087918 was associated with a decreased breast cancer risk in a Chinese population: a case-control study

10.21203/rs.2.22717/v1 ◽

2020 ◽

Author(s):

Yi Zheng ◽

Meng Wang ◽

Shuqian Wang ◽

Peng Xu ◽

Yujiao Deng ◽

...

Keyword(s):

Breast Cancer ◽

Structure Prediction ◽

Case Control Study ◽

Cancer Susceptibility ◽

Statistical Significance ◽

Breast Cancer Susceptibility ◽

Case Control ◽

Receptor Expression ◽

Breast Cancer Patients ◽

Control Study

Abstract Background LncRNA MEG3 expressed abnormally in various cancers including breast cancer, but no studies reported the correlation between MEG3 SNPs and breast cancer susceptibility. Methods This study is aimed to explore the association between three SNPs of MEG3 (rs3087918, rs7158663, rs11160608) and breast cancer. The study is a population-based case-control study including 434 breast cancer patients and 700 healthy controls. Genotyping was performed using Sequence MassArray technique. Function prediction of rs3087918 were based on RNAfold and lncRNASNP2 databases. Results Pooled analysis indicated that rs3087918 was related to a decreased risk of breast cancer (GG vs. TT: P = 0.042; GG vs. TT + TG: P = 0.046), especially for women aged 49 and above (GG vs. TT: P = 0.02). Comparison between case groups showed genotype GG and TG/GG of rs3087918 were correlated with her-2 receptor expression (GG vs. TT: P = 0.010; TG + GG vs. TT: P = 0.045). We didn’t find statistical significance for rs11160608, rs7158663 and breast cancer. Structure prediction based on RNAfold found rs3087918 may influence the secondary structure of MEG3. The results based on lncRNASNP2 indicated rs3087918 may gain the targets of hsa-miR-1203 to MEG3, while loss the target of hsa-miR-139-3p and hsa-miR-5091 to MEG3. Conclusions MEG3 rs3087918 was associated with a decreased risk of breast cancer. MEG3 haplotype TCG (SNP sequence: rs3087918, rs11160608, rs7158663) may increase the risk of breast cancer. And the protest effect of rs3087918 on breast cancer may owe to its effect on the structure and function of MEG3.

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Impact of Cyp1A1 and Comt Genotypes on Breast Cancer Risk in Mexican Women: A Pilot Study

The International Journal of Biological Markers ◽

10.1177/172460081002500306 ◽

2010 ◽

Vol 25 (3) ◽

pp. 157-163 ◽

Cited By ~ 7

Author(s):

Mónica Moreno-Galván ◽

Norma Estela Herrera-González ◽

Vera Robles-Pérez ◽

Julio C. Velasco-Rodríguez ◽

Roberto Tapia-Conyer ◽

...

Keyword(s):

Breast Cancer ◽

Case Control Study ◽

Cancer Susceptibility ◽

Breast Cancer Susceptibility ◽

Case Control ◽

Mexican Women ◽

Healthy Controls ◽

Breast Cancer Patients ◽

Pcr Rflp ◽

Control Study

Background Data suggest that estrogen-metabolizing genes may be involved in breast cancer carcinogenesis. Objective The aim of this study was to determine the association of CYP1A1 and COMT polymorphisms with this disease. Material and methods: A pilot case-control study was conducted with Mexican women. Ninety-one breast cancer patients and 94 healthy controls were selected. Epidemiological and clinical questionnaires were answered by all participants, and genotyping data were obtained. CYP1A1 3801 T>C (rs4646903), CYP1A1 4889 A>G (rs1048943) and COMT 1947 G>A (rs4680) polymorphisms were analyzed by PCR-RFLP. Results The results showed a high risk of breast cancer in women carrying the CYP1A1 (3801 T>C) m2/m2 genotype (OR=2.52; 95%CI=1.04–6.08). The risk was higher in postmenopausal women (OR=3.38; 95%CI=1.05–10.87). No association between COMT 1947 G>A (rs4680) or CYP1A1 4889 A>G (rs1048943) and breast cancer was found. Conclusions This study suggests that the CYP1A1 (3801 T>C) m2/m2 genotype may contribute to breast cancer susceptibility in Mexican women.

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