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Juras A, Crkvenac Gornik K, Held M, Sestan M, Turudic D, Sapina M, Srsen S, Huljev Frkovic S, Frkovic M, Gagro A, Jelusic M. Association of Glutathione Transferase M1, T1, P1 and A1 Gene Polymorphism and Susceptibility to IgA Vasculitis. Int J Mol Sci 2024; 25:7777. [PMID: 39063019 PMCID: PMC11277070 DOI: 10.3390/ijms25147777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Revised: 07/09/2024] [Accepted: 07/14/2024] [Indexed: 07/28/2024] Open
Abstract
Endothelial cell injury is a hallmark of IgA vasculitis (IgAV), possibly associated with various factors, including oxidative stress. Certain single nucleotide polymorphisms (SNPs) of glutathione S-transferases (GST) genes have been shown to increase susceptibility to oxidative stress. The objective of our study was to evaluate the gene polymorphisms of GSTM1, GSTT1, GSTP1, and GSTA1 in patients with IgAV. DNA was extracted from the blood of 124 children with IgAV and 168 age-matched healthy controls. A higher frequency of the GSTM1 null genotype was observed in patients with gastrointestinal (GI) system involvement compared to those without GI system involvement (51.5% vs. 28.6%, p = 0.011). Additionally, the GSTM1 null genotype was less prevalent (30.8% vs. 69.2%, p = 0.032), while the GSTP1 Val/Val genotype was significantly more prevalent in patients who developed urogenital complications (scrotal swelling) during the course of the disease (60% vs. 40%, p = 0.039). This study is the first to suggest an association between GSTM1 and GSTP1 polymorphisms and various phenotypes observed during the clinical course of IgAV in the pediatric population. However, it was performed on a national and likely single ethnic cohort, too small for definitive conclusions, so larger studies are needed to confirm this association.
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Affiliation(s)
- Ana Juras
- Department of Laboratory Diagnostics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, 10 000 Zagreb, Croatia; (A.J.); (K.C.G.)
| | - Kristina Crkvenac Gornik
- Department of Laboratory Diagnostics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, 10 000 Zagreb, Croatia; (A.J.); (K.C.G.)
| | - Martina Held
- Department of Paediatrics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, 10 000 Zagreb, Croatia; (M.H.); (M.S.); (D.T.); (S.H.F.); (M.F.)
| | - Mario Sestan
- Department of Paediatrics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, 10 000 Zagreb, Croatia; (M.H.); (M.S.); (D.T.); (S.H.F.); (M.F.)
| | - Daniel Turudic
- Department of Paediatrics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, 10 000 Zagreb, Croatia; (M.H.); (M.S.); (D.T.); (S.H.F.); (M.F.)
| | - Matej Sapina
- Department of Paediatrics, University Hospital Centre Osijek, Medical Faculty Osijek, Josip Juraj Strossmayer University of Osijek, 31 000 Osijek, Croatia;
| | - Sasa Srsen
- Department of Paediatrics, University of Split School of Medicine, University Hospital Centre Split, 21 000 Split, Croatia;
| | - Sanda Huljev Frkovic
- Department of Paediatrics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, 10 000 Zagreb, Croatia; (M.H.); (M.S.); (D.T.); (S.H.F.); (M.F.)
| | - Marijan Frkovic
- Department of Paediatrics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, 10 000 Zagreb, Croatia; (M.H.); (M.S.); (D.T.); (S.H.F.); (M.F.)
| | - Alenka Gagro
- Medical Faculty Osijek, Josip Juraj Strossmayer University of Osijek, 31 000 Osijek, Croatia;
- Department of Paediatrics, Children’s Hospital Zagreb, 10 000 Zagreb, Croatia
| | - Marija Jelusic
- Department of Paediatrics, University of Zagreb School of Medicine, University Hospital Centre Zagreb, 10 000 Zagreb, Croatia; (M.H.); (M.S.); (D.T.); (S.H.F.); (M.F.)
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Tiongco RE, Cayanan ND, Catacata M, Dominguez MJ. Ile105Val polymorphism in the GSTP1 gene is associated with susceptibility to acute myeloid leukemia: an updated systematic review and meta-analysis. Biomarkers 2024; 29:134-142. [PMID: 38428950 DOI: 10.1080/1354750x.2024.2326538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Accepted: 02/28/2024] [Indexed: 03/03/2024]
Abstract
BACKGROUND AND OBJECTIVE Several genetic variations are associated with acute myeloid leukemia (AML) susceptibility, including the GSTP1 Ile105Val polymorphism. Even with the existing meta-analysis conducted on the topic, no consensus has been reached since none of the studies available performed in-depth data analysis. Hence, we performed an updated systematic review and meta-analysis in this paper to obtain more precise estimates. MATERIALS AND METHODS We searched various databases and calculated the odds ratio (OR) and 95% confidence interval (CI) to examine whether the GSTP1 Ile105Val polymorphism is associated with AML susceptibility. Further statistical analysis was also done to obtain more accurate and reliable findings. RESULTS A total of 15 studies are included in the systematic review, but only 9 were included in the meta-analysis due to the studies deviating from the Hardy-Weinberg equilibrium. The analysis showed significantly increased susceptibility to AML in the allelic, co-dominant, and recessive models. Furthermore, subgroup analysis noted increased AML susceptibility in the non-Asian population. Comparing the proportions of the genotypes and alleles showed a significantly higher proportion of the Val/Val genotype and Val allele in the non-Asian cohort. CONCLUSION The GSTP1 Ile105Val polymorphism is significantly associated with AML susceptibility, especially among non-Asians. Further investigation should be performed to strengthen the current results.
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Affiliation(s)
- Raphael Enrique Tiongco
- Department of Medical Technology, College of Allied Medical Professions, Angeles University Foundation, Angeles City, Philippines
| | - Neil David Cayanan
- Department of Medical Technology, College of Allied Medical Professions, Angeles University Foundation, Angeles City, Philippines
| | - Miljun Catacata
- Department of Medical Technology, College of Allied Medical Professions, Angeles University Foundation, Angeles City, Philippines
| | - Michael John Dominguez
- Department of Medical Technology, College of Allied Medical Professions, Angeles University Foundation, Angeles City, Philippines
- School of Medicine, Angeles University Foundation, Angeles City, Philippines
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Obaidat D, Giordo R, Kleinbrink EL, Banisad E, Grossman LI, Arshad R, Stark A, Maroun MC, Lipovich L, Fernandez-Madrid F. Non-coding regions of nuclear-DNA-encoded mitochondrial genes and intergenic sequences are targeted by autoantibodies in breast cancer. Front Genet 2023; 13:970619. [PMID: 37082114 PMCID: PMC10111166 DOI: 10.3389/fgene.2022.970619] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Accepted: 11/15/2022] [Indexed: 03/31/2023] Open
Abstract
Autoantibodies against mitochondrial-derived antigens play a key role in chronic tissue inflammation in autoimmune disorders and cancers. Here, we identify autoreactive nuclear genomic DNA (nDNA)-encoded mitochondrial gene products (GAPDH, PKM2, GSTP1, SPATA5, MFF, TSPOAP1, PHB2, COA4, and HAGH) recognized by breast cancer (BC) patients’ sera as nonself, supporting a direct relationship of mitochondrial autoimmunity to breast carcinogenesis. Autoreactivity of multiple nDNA-encoded mitochondrial gene products was mapped to protein-coding regions, 3’ untranslated regions (UTRs), as well as introns. In addition, autoantibodies in BC sera targeted intergenic sequences that may be parts of long non-coding RNA (lncRNA) genes, including LINC02381 and other putative lncRNA neighbors of the protein-coding genes ERCC4, CXCL13, SOX3, PCDH1, EDDM3B, and GRB2. Increasing evidence indicates that lncRNAs play a key role in carcinogenesis. Consistent with this, our findings suggest that lncRNAs, as well as mRNAs of nDNA-encoded mitochondrial genes, mechanistically contribute to BC progression. This work supports a new paradigm of breast carcinogenesis based on a globally dysfunctional genome with altered function of multiple mitochondrial and non-mitochondrial oncogenic pathways caused by the effects of autoreactivity-induced dysregulation of multiple genes and their products. This autoimmunity-based model of carcinogenesis will open novel avenues for BC treatment.
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Affiliation(s)
- Deya Obaidat
- Department of Internal Medicine, Division of Rheumatology, Wayne State University School of Medicine, Detroit, MI, United States
| | - Roberta Giordo
- Department of Basic Medical Sciences, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
| | - Erica L. Kleinbrink
- Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, United States
- Quantitative Life Sciences, McGill University, Montreal, QC, Canada
| | - Emilia Banisad
- Department of Internal Medicine, Division of Rheumatology, Wayne State University School of Medicine, Detroit, MI, United States
| | - Lawrence I. Grossman
- Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, United States
| | - Rooshan Arshad
- Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, United States
| | - Azadeh Stark
- Department of Pathology, Henry Ford Health System, Detroit, MI, United States
| | - Marie-Claire Maroun
- Department of Internal Medicine, Division of Rheumatology, Wayne State University School of Medicine, Detroit, MI, United States
| | - Leonard Lipovich
- Department of Basic Medical Sciences, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates
- Shenzhen Huayuan Biotechnology Co. Ltd, Shenzhen Huayuan Biological Science Research Institute, Shenzhen, Guangdong, China
- *Correspondence: Leonard Lipovich, ; Félix Fernandez-Madrid,
| | - Félix Fernandez-Madrid
- Department of Internal Medicine, Division of Rheumatology, Wayne State University School of Medicine, Detroit, MI, United States
- Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, United States
- Karmanos Cancer Institute, Wayne State University, Detroit, MI, United States
- *Correspondence: Leonard Lipovich, ; Félix Fernandez-Madrid,
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Rasheed MN, Hazim Hamoode R, Adnan Abdul-Jalil A. Association of glutathione S-transferase 1 (GSTP1) polymorphisms with Breast Cancer susceptibility. BIONATURA 2022. [DOI: 10.21931/rb/2022.07.03.42] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Hereditary and environmental variables have a role in the development of breast cancer. This study aimed to examine the links between genetic Variations in the GSTP1 gene and Predisposition to breast cancer in an Iraqi population. The research included 40 Iraqi female breast cancer patients and 20 healthy volunteers. GSTP1-1695 A/G gene polymorphisms were investigated using polymerase chain reaction in Real-time (RT-PCR). The results showed the GSTP1 frequency of the wild GG genotypes was showed significantly (P<0.01) higher in healthy women in comparison with Breast cancer women (GG, 80% vs. 32.5%, respectively; furthermore, heterozygous AG genotypes were significantly higher in Breast cancer women in comparison with healthy women 42.5% vs. 20%, respectively at (P<0.01). While the mutant AA genotype (25%) in patient women appeared significantly (P<0.01) higher compared to healthy women (0.0%). Finally, we discovered a connection between GSTP1 polymorphisms and a higher chance of developing breast cancer in an Iraqi female population sample.
Keywords: glutathione S-transferase1, breast cancer, polymorphism.
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Affiliation(s)
- Marrib N. Rasheed
- University Of Baghdad / Institute of Genetic Engineering and Biotechnology for Postgraduate Studies, Iraq
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Dos Santos SP, Morissugui SS, Gimenez Martins APD, Fernandes GMDM, Russo A, Galbiatti-Dias ALS, Castanhole-Nunes MMU, Francisco JLE, Pavarino ÉC, Goloni-Bertollo EM. Evaluation of molecular markers GSTM1 and GSTT1 and clinical factors in breast cancer: case-control study and literature review. Xenobiotica 2021; 51:1326-1334. [PMID: 34096444 DOI: 10.1080/00498254.2021.1938291] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The study was conducted to evaluate the frequency of polymorphisms in GSTM1 and GSTT1 genes in patients with breast cancer compared with individuals without history of cancer, and the association of these polymorphisms with clinical/epidemiological parameters.There were evaluated 752 women (219 patients and 533 controls). Molecular analysis was performed by the Polymerase Chain Reaction (PCR). Statistical analysis was used multiple logistic regression and descriptive statistics.Age ≥50 years (OR =3.22, 95% CI =2.30 - 4.51, p <0.001) and alcohol consumption (OR =1.60, 95% CI =1.13 - 2.27, p = 0.008) were associated to the development of breast cancer, while smoking and null genotypes GSTM1 and GSTT1 presented no association. GSTM1 and GSTT1 polymorphisms presented no relationship with the clinical and histopathological parameters or molecular subtypes of breast cancer. Ninety-two percent of tumors were invasive ductal, 66% were grade II, 65% were larger than 2 cm, the stages II (35.3%) and III (31.2%) were the most prevalent, and 47.7% were molecular subtype luminal B.Individuals aged ≥50 years and alcohol consumers have more chance to developing breast cancer. GSTM1 and GSTT1 polymorphisms are not associated to the risk of breast cancer.
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Affiliation(s)
- Stéphanie Piacenti Dos Santos
- Molecular Biology: Genetics and Molecular Biology Research Unit, São José do Rio Preto Medical School - FAMERP, São Jose do Rio Preto/SP, Brazil
| | - Sabrina Sayuri Morissugui
- Molecular Biology: Genetics and Molecular Biology Research Unit, São José do Rio Preto Medical School - FAMERP, São Jose do Rio Preto/SP, Brazil
| | - Ana Paula D'Alarme Gimenez Martins
- Molecular Biology: Genetics and Molecular Biology Research Unit, São José do Rio Preto Medical School - FAMERP, São Jose do Rio Preto/SP, Brazil
| | - Glaucia Maria de Mendonça Fernandes
- Molecular Biology: Genetics and Molecular Biology Research Unit, São José do Rio Preto Medical School - FAMERP, São Jose do Rio Preto/SP, Brazil
| | - Anelise Russo
- Molecular Biology: Genetics and Molecular Biology Research Unit, São José do Rio Preto Medical School - FAMERP, São Jose do Rio Preto/SP, Brazil
| | - Ana Lívia Silva Galbiatti-Dias
- Molecular Biology: Genetics and Molecular Biology Research Unit, São José do Rio Preto Medical School - FAMERP, São Jose do Rio Preto/SP, Brazil
| | | | - José Luis Esteves Francisco
- Gynecology and Obstetrics Department, São José do Rio Preto Medical School Fundation - FAMERP/FUNFARME, São José do Rio Preto/SP, Brazil.,São José do Rio Preto Medical School Fundation - FUNFARME, São José do Rio Preto, SP, Brazil
| | - Érika Cristina Pavarino
- Molecular Biology: Genetics and Molecular Biology Research Unit, São José do Rio Preto Medical School - FAMERP, São Jose do Rio Preto/SP, Brazil.,São José do Rio Preto Medical School Fundation - FUNFARME, São José do Rio Preto, SP, Brazil
| | - Eny Maria Goloni-Bertollo
- Molecular Biology: Genetics and Molecular Biology Research Unit, São José do Rio Preto Medical School - FAMERP, São Jose do Rio Preto/SP, Brazil.,São José do Rio Preto Medical School Fundation - FUNFARME, São José do Rio Preto, SP, Brazil
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Association of GSTP1 p.Ile105Val (rs1695, c.313A > G) Variant with the Risk of Breast Carcinoma among Egyptian Women. Biochem Genet 2021; 59:1487-1505. [PMID: 33939082 DOI: 10.1007/s10528-021-10070-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 04/19/2021] [Indexed: 01/01/2023]
Abstract
Several reports examined the association of the GSTP1 p.Ile105Val (rs1695, c.313A > G) variant with the elevated risk of multiple cancerous diseases involving breast carcinoma, but with inconclusive findings. The primary purpose of this study is to test the association of this essential variant with the risk of breast carcinoma among Egyptian females. This case-control study was conducted based on 200 participants involving 100 women diagnosed with breast carcinoma and 100 unrelated cancer-free controls from the same district. The genomic DNA for all participants was genotyped utilizing T-ARMS-PCR procedure. The frequencies of the GSTP1 p.Ile105Val (rs1695, c.313A > G) variant indicated a statistically significant with the elevated risk of breast carcinoma under various genetic models, including allelic (OR = 2.48, P-value < 0.001) and dominant (OR = 2.36, P-value = 0.003) models. In conclusion, the GSTP1 p.Ile105Val (rs1695, c.313A > G) variant was considered as an independent risk factor for breast carcinoma among Egyptian women.
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Boujemaa M, Hamdi Y, Mejri N, Romdhane L, Ghedira K, Bouaziz H, El Benna H, Labidi S, Dallali H, Jaidane O, Ben Nasr S, Haddaoui A, Rahal K, Abdelhak S, Boussen H, Boubaker MS. Germline copy number variations in BRCA1/2 negative families: Role in the molecular etiology of hereditary breast cancer in Tunisia. PLoS One 2021; 16:e0245362. [PMID: 33503040 PMCID: PMC7840007 DOI: 10.1371/journal.pone.0245362] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Accepted: 12/28/2020] [Indexed: 12/24/2022] Open
Abstract
Hereditary breast cancer accounts for 5-10% of all breast cancer cases. So far, known genetic risk factors account for only 50% of the breast cancer genetic component and almost a quarter of hereditary cases are carriers of pathogenic mutations in BRCA1/2 genes. Hence, the genetic basis for a significant fraction of familial cases remains unsolved. This missing heritability may be explained in part by Copy Number Variations (CNVs). We herein aimed to evaluate the contribution of CNVs to hereditary breast cancer in Tunisia. Whole exome sequencing was performed for 9 BRCA negative cases with a strong family history of breast cancer and 10 matched controls. CNVs were called using the ExomeDepth R-package and investigated by pathway analysis and web-based bioinformatic tools. Overall, 483 CNVs have been identified in breast cancer patients. Rare CNVs affecting cancer genes were detected, of special interest were those disrupting APC2, POU5F1, DOCK8, KANSL1, TMTC3 and the mismatch repair gene PMS2. In addition, common CNVs known to be associated with breast cancer risk have also been identified including CNVs on APOBECA/B, UGT2B17 and GSTT1 genes. Whereas those disrupting SULT1A1 and UGT2B15 seem to correlate with good clinical response to tamoxifen. Our study revealed new insights regarding CNVs and breast cancer risk in the Tunisian population. These findings suggest that rare and common CNVs may contribute to disease susceptibility. Those affecting mismatch repair genes are of interest and require additional attention since it may help to select candidates for immunotherapy leading to better outcomes.
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Affiliation(s)
- Maroua Boujemaa
- Laboratory of Biomedical Genomics and Oncogenetics, LR16IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Yosr Hamdi
- Laboratory of Biomedical Genomics and Oncogenetics, LR16IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia
- Laboratory of Human and Experimental Pathology, Institut Pasteur de Tunis, Tunis, Tunisia
| | - Nesrine Mejri
- Laboratory of Biomedical Genomics and Oncogenetics, LR16IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia
- Medical Oncology Department, Abderrahman Mami Hospital, Faculty of Medicine Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Lilia Romdhane
- Laboratory of Biomedical Genomics and Oncogenetics, LR16IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia
- Department of Biology, Faculty of Science of Bizerte, University of Carthage, Jarzouna, Tunisia
| | - Kais Ghedira
- Laboratory of Bioinformatics, Biomathematics and Biostatistics, LR16IPT09, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Hanen Bouaziz
- Laboratory of Biomedical Genomics and Oncogenetics, LR16IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia
- Surgical Oncology Department, Salah Azaiez Institute of Cancer, Tunis, Tunisia
| | - Houda El Benna
- Laboratory of Biomedical Genomics and Oncogenetics, LR16IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia
- Medical Oncology Department, Abderrahman Mami Hospital, Faculty of Medicine Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Soumaya Labidi
- Laboratory of Biomedical Genomics and Oncogenetics, LR16IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia
- Medical Oncology Department, Abderrahman Mami Hospital, Faculty of Medicine Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Hamza Dallali
- Laboratory of Biomedical Genomics and Oncogenetics, LR16IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Olfa Jaidane
- Surgical Oncology Department, Salah Azaiez Institute of Cancer, Tunis, Tunisia
| | - Sonia Ben Nasr
- Department of Medical Oncology, Military Hospital of Tunis, Tunis, Tunisia
| | | | - Khaled Rahal
- Surgical Oncology Department, Salah Azaiez Institute of Cancer, Tunis, Tunisia
| | - Sonia Abdelhak
- Laboratory of Biomedical Genomics and Oncogenetics, LR16IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia
| | - Hamouda Boussen
- Laboratory of Biomedical Genomics and Oncogenetics, LR16IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia
- Medical Oncology Department, Abderrahman Mami Hospital, Faculty of Medicine Tunis, University Tunis El Manar, Tunis, Tunisia
| | - Mohamed Samir Boubaker
- Laboratory of Biomedical Genomics and Oncogenetics, LR16IPT05, Institut Pasteur de Tunis, University of Tunis El Manar, Tunis, Tunisia
- Laboratory of Human and Experimental Pathology, Institut Pasteur de Tunis, Tunis, Tunisia
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Rajagopal T, Seshachalam A, Rathnam KK, Jothi A, Talluri S, Venkatabalasubramanian S, Dunna NR. Impact of xenobiotic-metabolizing gene polymorphisms on breast cancer risk in South Indian women. Breast Cancer Res Treat 2021; 186:823-837. [PMID: 33392841 DOI: 10.1007/s10549-020-06028-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 11/16/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND Functional variants of the xenobiotic-metabolizing genes (XMG) might modulate breast cancer (BC) risk by altering the rate of metabolism and clearance of myriad types of potent carcinogens from the breast tissue. Despite mounting evidence on the role of XMG variants on BC risk, the current knowledge regarding their influence on BC development is still fragmentary. METHODS The present study examined the candidate genetic variants in CYP1A1, NQO1, GST-T1, GST-M1, and GST-P1 in 1002 subjects (502 BC patients and 500 disease-free women). PCR-RFLP was employed to genotype the mono-nucleotide variation in CYP1A1, NQO1, and GST-P1, and allele-specific PCR was used to detect the deletion polymorphism in GST-T1 and GST-M1 genes. RESULTS Regarding CYP1A1-M1 polymorphism, the heterozygous TC and mutant CC genotype conferred 1.47-fold (95% CI 1.13-1.91, p = 0.004) and 1.84-fold (95% CI 1.17-2.91, p = 0.009) elevated risk of BC. GST-T1 null genotype was associated with increased BC risk (OR 1.47; 95% CI 1.02-2.11, p = 0.037). For the NQO1 C609T variant, the mutant T allele was associated with BC risk with an odds ratio of 1.22 (95% CI 1.02-1.48, p = 0.034). Combinatorial analysis indicated that the presence of NQO1*2 (CT), CYP1A1-M1 (CC), and GST-P1 rs1695 (AG) genotypes conferred 16.7-fold elevated risk of BC (95% CI 3.65-76.85; p < 0.001). Moreover, GST-M1 null genotype was associated with the development of larger primary breast tumors. CONCLUSION Xenobiotic-metabolizing gene polymorphisms may play a crucial role in mammary carcinogenesis in South Indian women.
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Affiliation(s)
- Taruna Rajagopal
- Cancer Genomics Laboratory, Department of Biotechnology, School of Chemical and Biotechnology, SASTRA - Deemed University, Thanjavur, 613 401, India
| | - Arun Seshachalam
- Department of Medical and Paediatric Oncology, Dr.G.V.N Cancer Institute, Singarathope, Trichy, 620 008, India
| | - Krishna Kumar Rathnam
- Department of Hemato Oncology - Medical Oncology and Bone Marrow Transplantation, Meenakshi Mission Hospital & Research Centre, Madurai, 625 107, India
| | - Arunachalam Jothi
- Department of Bioinformatics, School of Chemical and Biotechnology, SASTRA - Deemed University, Thanjavur, 613 401, India
| | - Srikanth Talluri
- Dana Farber Cancer Institute, Boston, MA, 02215, USA.,Veterans Administration Boston Healthcare System, West Roxbury, MA, 02132, USA
| | - Sivaramakrishnan Venkatabalasubramanian
- Department of Genetic Engineering, Faculty of Engineering and Technology, SRM Institute of Medical Science and Technology, Kattankulathur Campus, Chennai, 603 203, India
| | - Nageswara Rao Dunna
- Cancer Genomics Laboratory, Department of Biotechnology, School of Chemical and Biotechnology, SASTRA - Deemed University, Thanjavur, 613 401, India.
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9
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Madrid FF, Grossman LI, Aras S. Mitochondria Autoimmunity and MNRR1 in Breast Carcinogenesis: A Review. JOURNAL OF CANCER IMMUNOLOGY 2020; 2:138-158. [PMID: 33615312 PMCID: PMC7894625 DOI: 10.33696/cancerimmunol.2.027] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
We review here the evidence for participation of mitochondrial autoimmunity in BC inception and progression and propose a new paradigm that may challenge the prevailing thinking in oncogenesis by suggesting that mitochondrial autoimmunity is a major contributor to breast carcinogenesis and probably to the inception and progression of other solid tumors. It has been shown that MNRR1 mediated mitochondrial-nuclear function promotes BC cell growth and migration and the development of metastasis and constitutes a proof of concept supporting the participation of mitochondrial autoimmunity in breast carcinogenesis. The resemblance of the autoantibody profile in BC detected by IFA with that in the rheumatic autoimmune diseases suggested that studies on the autoantibody response to tumor associated antigens and the characterization of the mtDNA- and nDNA-encoded antigens may provide functional data on breast carcinogenesis. We also review the studies supporting the view that a panel of autoreactive nDNA-encoded mitochondrial antigens in addition to MNRR1 may be involved in breast carcinogenesis. These include GAPDH, PKM2, GSTP1, SPATA5, MFF, ncRNA PINK1-AS/DDOST as probably contributing to BC progression and metastases and the evidence suggesting that DDX21 orchestrates a complex signaling network with participation of JUND and ATF3 driving chronic inflammation and breast tumorigenesis. We suggest that the widespread autoreactivity of mtDNA- and nDNA-encoded mitochondrial proteins found in BC sera may be the reflection of autoimmunity triggered by mitochondrial and non-mitochondrial tumor associated antigens involved in multiple tumorigenic pathways. Furthermore, we suggest that mitochondrial proteins may contribute to mitochondrial dysfunction in BC even if mitochondrial respiration is found to be within normal limits. However, although the studies show that mitochondrial autoimmunity is a major factor in breast cancer inception and progression, it is not the only factor since there is a multiplex autoantibody profile targeting centrosome and stem cell antigens as well as anti-idiotypic antibodies, revealing the complex signaling network involved in breast carcinogenesis. In summary, the studies reviewed here open new, unexpected therapeutic avenues for cancer prevention and treatment of patients with cancer derived from an entirely new perspective of breast carcinogenesis.
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Affiliation(s)
- Félix Fernández Madrid
- Department of Medicine, Division of Rheumatology, Wayne State University School of Medicine, Detroit, MI 48201 USA
- Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201 USA
- Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201 USA
| | - Lawrence I. Grossman
- Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201 USA
| | - Siddhesh Aras
- Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201 USA
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10
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A decade in unravelling the etiology of gastric carcinogenesis in Kashmir, India – A high risk region. GENE REPORTS 2020. [DOI: 10.1016/j.genrep.2020.100832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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11
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Silencing of long non-coding RNA LINC01270 inhibits esophageal cancer progression and enhances chemosensitivity to 5-fluorouracil by mediating GSTP1methylation. Cancer Gene Ther 2020; 28:471-485. [PMID: 33199829 DOI: 10.1038/s41417-020-00232-1] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 08/28/2020] [Accepted: 09/21/2020] [Indexed: 12/17/2022]
Abstract
Esophageal cancer (EC) is a serious digestive malignancy which remains the sixth leading cause of cancer-related deaths worldwide. Emerging evidence suggests the involvement of long non-coding RNAs (lncRNAs) in the tumorigenesis of EC and thus, in this study we explored the potential effects of lncRNA LINC01270 on EC cell proliferation, migration, invasion and, drug resistance via regulation of glutathione S-transferase P1 (GSTP1) methylation. First, we screened out the EC-related differentially expressed lncRNAs, and the expression of our top candidate LINC01270 was quantified in EC tissues and cells. To define the role of LINC01270 in EC progression, we evaluated the proliferation, migration and invasion of EC cells when the LINC01270 was overexpressed or knocked down, in the presence of the GSTP1 methylation inhibitor SGI-1027 and 5-fluorouracil (5-FU). In addition, interaction between LINC01270 and methylation of the GSTP1 promoter was identified. Finally, we assessed transplantable tumor growth in nude mice. LINC01270 was up-regulated and GSTP1 was down-regulated in EC tissues and cells. Silencing of LINC01270 inhibited migration and invasion, and enhanced the sensitivity of 5-FU in EC cells. We found that LINC01270 recruited the DNA methyltransferases DNMT1, DNMT3A and DNMT3B initiating GSTP1 promoter methylation, thereby leading to the proliferation, migration, invasion and drug resistance of EC cells. Moreover, GSTP1 overexpression was observed to reverse the effects of LINC01270 overexpression on EC cells and their response to 5-FU. Taken together, this study shows that inhibition of LINC01270 can lead to suppression of EC progression via demethylation of GSTP1, highlighting this lncRNA as a potential target for EC treatment.
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Lei K, Xia Y, Wang XC, Ahn EH, Jin L, Ye K. C/EBPβ mediates NQO1 and GSTP1 anti-oxidative reductases expression in glioblastoma, promoting brain tumor proliferation. Redox Biol 2020; 34:101578. [PMID: 32526700 PMCID: PMC7287278 DOI: 10.1016/j.redox.2020.101578] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Accepted: 05/10/2020] [Indexed: 12/20/2022] Open
Abstract
Glioblastoma (GBM) is the most common and most aggressive brain tumor, associated with high levels of reactive oxidative species (ROS) due to metabolic and signaling aberrations. High ROS levels are detrimental to cells, but it remains incompletely understood how cancer cells cope with the adverse effects. Here we show that C/EBPβ, a ROS responsive transcription factor, regulates the transcription of NQO1 and GSTP1, two antioxidative reductases, which neutralize ROS in the GBM and mediates their proliferation. C/EBPβ is upregulated in EGFR overexpressed GBM cells, inversely correlated with the survival rates of brain tumor patients. Interestingly, C/EBPβ binds the promoters of NQO1 and GSTP1 and escalates their expression. Overexpression of C/EBPβ selectively decreases the ROS in EGFR-overexpressed U87MG cells and promotes cell proliferation via upregulating NQO1 and GSTP1; whereas knocking down C/EBPβ elevates the ROS and reduces proliferation by repressing the reductases. Accordingly, C/EBPβ mediates the brain tumor growth in vivo, coupling with NQO1 and GSTP1 expression and ROS levels. Hence, C/EBPβ regulates the expression of antioxidative reductases and balances the ROS, promoting brain tumor proliferation.
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Affiliation(s)
- Kecheng Lei
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA; Neurotoxin Research Center of Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Neurological Department of Tongji Hospital, Tongji University School of Medicine, 200065, Shanghai, China
| | - Yiyuan Xia
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA; Department of Pathophysiology, Key Laboratory of Ministry of Education of Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Xiao-Chuan Wang
- Department of Pathophysiology, Key Laboratory of Ministry of Education of Neurological Diseases, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Eun Hee Ahn
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Lingjing Jin
- Neurotoxin Research Center of Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Neurological Department of Tongji Hospital, Tongji University School of Medicine, 200065, Shanghai, China.
| | - Keqiang Ye
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
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Miao LF, Ye XH, He XF. Individual and combined effects of GSTM1, GSTT1, and GSTP1 polymorphisms on breast cancer risk: A meta-analysis and re-analysis of systematic meta-analyses. PLoS One 2020; 15:e0216147. [PMID: 32155154 PMCID: PMC7064184 DOI: 10.1371/journal.pone.0216147] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2018] [Accepted: 04/15/2019] [Indexed: 12/14/2022] Open
Abstract
Background Fourteen previous meta-analyses have been published to analyze the polymorphisms of individual GSTM1 present/null, GSTT1 present/null, and GSTP1 IIe105Val on breast cancer (BC) risk. However, their meta-analyses did not explore the combined effects of the three genetic polymorphisms on BC risk. In addition, they did not evaluate the credibility of statistically significant associations. Furthermore, a multitude of new articles have been published on these themes, and therefore a meta-analysis and re-analysis of systematic previous meta-analyses were performed to further explore these issues. Objectives To determine the association between the individual and combined effects of GSTM1, GSTT1, and GSTP1 polymorphisms on breast cancer risk. Methods Crude odds ratios (ORs) and their 95% confidence intervals (CIs) were applied to estimate the association between individual and combined effects of GSTM1, GSTT1, and GSTP1 polymorphisms on BC risk. To evaluate the credibility of statistically significant associations in the current and previous meta-analyses, we applied the the false-positive report probabilities (FPRP) test and the Venice criteria. Results 101 publications were selected to evaluate the individual and combined effects of GSTM1, GSTT1 and GSTP1 polymorphisms on BC risk. Overall, statistically significant elevated BC risk was found in any individual and combined effects of GSTM1 present/null, GSTT1 present/null, and GSTP1 IIe105Val polymorphisms. However, when we restricted studies only involving with high-quality, matching, HWE, and genotyping examination performed blindly or with quality control, significantly increased BC risk was only found in overall population for GSTM1 null genotype, among all populations, Caucasians, and postmenopausal women for the combined effects of GSTM1 and GSTT1 polymorphisms, and in overall analysis for the combined effects of GSTM1, GSTT1, and GSTP1 IIe105Val polymorphisms. Further, less-credible positive results were identified when we evaluated the credibility of positive results of the current and previous meta-analyses. Conclusions This meta-analysis indicates that the individual and combined effects of GSTM1, GSTT1 and GSTP1 polymorphisms may be not associated with increased BC risk.
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Affiliation(s)
- Li-Feng Miao
- Department of Galactophore, Heping Hospital Affiliated to Changzhi Medical College, Shanxi, Changzhi, China
| | - Xiang-Hua Ye
- Department of Radiotherapy, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiao-Feng He
- Department of Science and Education, Heping Hospital Affiliated to Changzhi Medical College, Shanxi, Changzhi, China
- * E-mail:
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14
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Miao LF, Wang XY, Ye XH, Cui MS, He XF. Combined effects of GSTM1 and GSTT1 polymorphisms on breast cancer risk: A MOOSE-compliant meta-analysis and false-positive report probabilities test. Medicine (Baltimore) 2019; 98:e14333. [PMID: 30732156 PMCID: PMC6380837 DOI: 10.1097/md.0000000000014333] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Many molecular epidemiology studies have reported an association between the combined effects of glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) polymorphisms on breast cancer risk. However, the results have been controversial.A meta-analysis was performed to clarify this issue.Meta-analysis of observational studies in epidemiology guidelines was used. Pooled the crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model or fixed-effects model. Several subgroup analyses were conducted by ethnicity, source of control, matching, and menopausal status. In addition, we also performed sensitivity analysis and publication bias. Moreover, a false-positive report probability (FPRP) test was applied to assess positive results.A significantly increased breast cancer risk was observed in overall population (GSTM1 null/GSTT1 present [- +] vs GSTM1 present/GSTT1 present [+ +]: OR = 1.19, 95% CI: 1.03-1.36, GSTM1 null/GSTT1 null [- -] vs + +: OR = 1.63, 95% CI: 1.29-2.06, (- +) + GSTM1 present/GSTT1 null (+ -) vs + +: OR = 1.17, 95% CI: 1.05-1.31, (- +) + (+ -) + (- -) vs + +: OR = 1.27, 95% CI: 1.12-1.44, and - - vs (- +) + (+ -) + (+ +): OR = 1.39, 95% CI: 1.17-1.66) and several subgroup analyses, such as Caucasians, Indians, postmenopausal women, and so on. However, positive results were only considered noteworthy in overall population (- - vs + +: FPRP = 0.150 and (- +) + (+ -) + (- -) vs + +: FPRP = 0.162). Moreover, no significant association was observed when we used the trim and fill method to adjust the pooled data from all populations. Further, none of positive results of sensitivity analysis were considered noteworthy (FPRP >0.2).These positive findings should be interpreted with caution and indicate that an increased breast cancer risk may most likely result from false-positive results, rather than from true associations or biological factors on the combined effects of GSTM1 and GSTT1. Future studies should be based on sample sizes well-powered and attention needs to be paid to study design to further identify this issue.
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Affiliation(s)
- Li-Feng Miao
- Department of Galactophore, Affiliated Heping Hospital, Changzhi Medical College, Shanxi, Changzhi
| | - Xiao-Yan Wang
- Department of Epidemiology and Health Statistics, Basic Medical College of Zhejiang University of Traditional Chinese Medicine
| | - Xiang-Hua Ye
- Department of Radiotherapy, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou
| | - Meng-Shen Cui
- Department of Galactophore, Affiliated Heping Hospital, Changzhi Medical College, Shanxi, Changzhi
| | - Xiao-Feng He
- Department of Science and Education, Affiliated Heping Hospital, Changzhi Medical College, Shanxi, Changzhi, PR China
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15
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Sacco J, Mann S, Toral K. Single nucleotide polymorphisms and microsatellites in the canine glutathione S-transferase pi 1 ( GSTP1) gene promoter. Canine Genet Epidemiol 2017; 4:9. [PMID: 29046813 PMCID: PMC5635497 DOI: 10.1186/s40575-017-0050-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2017] [Accepted: 09/19/2017] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Genetic polymorphisms within the glutathione S-transferase P1 (GSTP1) gene affect the elimination of toxic xenobiotics by the GSTP1 enzyme. In dogs, exposure to environmental chemicals that may be GSTP1 substrates is associated with cancer. The objectives of this study were to investigate the genetic variability in the GSTP1 promoter in a diverse population of 278 purebred dogs, compare the incidence of any variants found between breeds, and predict their effects on gene expression. To provide information on ancestral alleles, a number of wolves, coyotes, and foxes were also sequenced. RESULTS Fifteen single nucleotide polymorphisms (SNPs) and two microsatellites were discovered. Three of these loci were only polymorphic in dogs while three other SNPs were unique to wolves and coyotes. The major allele at c.-46 is T in dogs but is C in the wild canids. The c.-185 delT variant was unique to dogs. The microsatellite located in the 5' untranslated region (5'UTR) was a highly polymorphic GCC tandem repeat, consisting of simple and compound alleles that varied in size from 10 to 22-repeat units. The most common alleles consisted of 11, 16, and 17-repeats. The 11-repeat allele was found in 10% of dogs but not in the other canids. Unequal recombination and replication slippage between similar and distinct alleles may be the mechanism for the multiple microsatellites observed. Twenty-eight haplotypes were constructed in the dog, and an additional 8 were observed in wolves and coyotes. While the most common haplotype acrossbreeds was the wild-type *1A(17), other prevalent haplotypes included *3A(11) in Greyhounds, *6A(16) in Labrador Retrievers, *9A(16) in Golden Retrievers, and *8A(19) in Standard Poodles. Boxers and Siberian Huskies exhibited minimal haplotypic diversity. Compared to the simple 16*1 allele, the compound 16*2 allele (found in 12% of dogs) may interfere with transcription factor binding and/or the stability of the GSTP1 transcript. CONCLUSIONS Dogs and other canids exhibit extensive variation in the GSTP1 promoter. Genetic polymorphisms within distinct haplotypes prevalent in certain breeds can affect GSTP1 expression and carcinogen detoxification, and thus may be useful as genetic markers for cancer in dogs.
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Affiliation(s)
- James Sacco
- Ellis Pharmacogenomics Laboratory, College of Pharmacy and Health Sciences, Drake University, Des Moines, IA 50311 USA
| | - Sarah Mann
- Ellis Pharmacogenomics Laboratory, College of Pharmacy and Health Sciences, Drake University, Des Moines, IA 50311 USA
| | - Keller Toral
- Ellis Pharmacogenomics Laboratory, College of Pharmacy and Health Sciences, Drake University, Des Moines, IA 50311 USA
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Wang W, Liu F, Wang C, Wang C, Tang Y, Jiang Z. Glutathione S-transferase A1 mediates nicotine-induced lung cancer cell metastasis by promoting epithelial-mesenchymal transition. Exp Ther Med 2017; 14:1783-1788. [PMID: 28810650 DOI: 10.3892/etm.2017.4663] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2016] [Accepted: 03/31/2017] [Indexed: 12/22/2022] Open
Abstract
The present study aimed to investigate the effect of glutathione S-transferase A1 (GSTA1) on lung cancer cell viability, invasion and adhesion in the presence of nicotine in vitro. Furthermore, the effect of GSTA1 on the epithelial-mesenchymal transition (EMT), a process strongly associated with lung cancer metastasis, was examined. Human lung carcinoma A549 cells were treated with various concentrations of nicotine (0.01, 0.1, 1 and 10 µM) and levels of GSTA1 mRNA and protein were measured by reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. To knock down GSTA1 expression, GSTA1-small interfering RNA was transfected into A549 cells. Cell viability, invasion and adhesion abilities were determined by MTT, Transwell-Matrigel invasion and cell adhesion assays, respectively. The expression of the epithelial cell markers E-cadherin and keratin, and the mesenchymal cell markers vimentin and N-cadherin in A549 cells were examined by western blot analysis. The current study indicated that the expression of GSTA1 was increased in A549 cells following nicotine treatment. GSTA1 suppression inhibited the viability, invasion and adhesion of lung cancer cells. In addition, the increase in lung cancer cell viability, invasion and adhesion by nicotine was suppressed following GSTA1 knockdown. Furthermore, GSTA1 affected the expression of EMT markers in nicotine-treated or untreated lung cancer cells. Thus the present study demonstrates that GSTA1 promotes lung cancer cell invasion and adhesion and mediates the effect of nicotine on lung cancer cell metastasis in vitro. Furthermore, the results demonstrated that GSTA1 exerts its effect on lung cancer cell metastasis by promoting the EMT.
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Affiliation(s)
- Wei Wang
- Department of Thoracic Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong 264000, P.R. China.,Department of Thoracic Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
| | - Feiyu Liu
- Department of Pharmacy, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong 264000, P.R. China
| | - Chaoyang Wang
- Department of Thoracic Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong 264000, P.R. China
| | - Chengde Wang
- Department of Thoracic Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong 264000, P.R. China
| | - Yijun Tang
- Department of Thoracic Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong 264000, P.R. China
| | - Zhongmin Jiang
- Department of Thoracic Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China
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17
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Xin X, Jin Z, Gu H, Li Y, Wu T, Hua T, Wang H. Association between glutathione S-transferase M1/T1 gene polymorphisms and susceptibility to endometriosis: A systematic review and meta-analysis. Exp Ther Med 2016; 11:1633-1646. [PMID: 27168783 PMCID: PMC4840522 DOI: 10.3892/etm.2016.3110] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2014] [Accepted: 02/11/2016] [Indexed: 11/06/2022] Open
Abstract
Endometriosis is a polygenic/multifactorial disease caused by interactions between multiple genes and the environment. Findings from studies evaluating the association between the glutathione S-transferase (GST) M1/T1 null genotype and susceptibility to endometriosis are inconsistent. This meta-analysis updated and reevaluated the possible associations between GSTM1, GSTT1 and combined GSTM1/GSTT1 (null genotype versus wild-type) gene polymorphisms and susceptibility to endometriosis. The PubMed, Embase and Chinese BioMedical Literature databases and Google Scholar were searched for case-control genetic association studies on GSTM1/GSTT1 (null genotype versus wild-type) gene polymorphisms and endometriosis in comparison with non-endometriosis or healthy controls. Fixed-effect and random-effect meta-analytical techniques were conducted for the outcome measure and subgroup analyses. The meta-analysis demonstrated significant associations between the GSTM1 [odds ratio (OR)=1.56; 95% confidence interval (CI): 1.25–1.95; P<0.0001), GSTT1 (OR=1.31; 95% CI: 1.02–1.68; P=0.037) and GSTM1/GSTT1 (OR=1.68; 95% CI: 1.29–2.17; P<0.0001) null genotypes and increased risk for endometriosis. The results suggest that the GSTM1, GSTT1, and combined GSTM1/GSTT1 null genotypes increase susceptibility to endometriosis. Additional well-designed studies and precise analyses are warranted to confirm these findings.
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Affiliation(s)
- Xiaoyan Xin
- Department of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Zhishan Jin
- Department of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Huajian Gu
- Department of General Surgery, Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou 550001, P.R. China
| | - Yuanyue Li
- Department of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Tingting Wu
- Department of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Teng Hua
- Department of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
| | - Hongbo Wang
- Department of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
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18
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Vivarelli F, Canistro D, Franchi P, Sapone A, Vornoli A, Della Croce C, Longo V, Lucarini M, Paolini M. Disruption of redox homeostasis and carcinogen metabolizing enzymes changes by administration of vitamin E to rats. Life Sci 2015; 145:166-73. [PMID: 26702769 DOI: 10.1016/j.lfs.2015.12.033] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2015] [Revised: 11/14/2015] [Accepted: 12/14/2015] [Indexed: 12/14/2022]
Abstract
AIMS A large meta-analysis of randomized clinical trials has seriously questioned chemoprevention based on vitamins including vitamin E (VE), and an increased risk for cancer among long-term users was actually seen. However, the mechanism underlying these findings still remain unknown. To clarify the mechanism, in an in vivo model we studied the putative disruption of redox homeostasis and the perturbation of carcinogen metabolizing enzymes determined by VE. MAIN METHODS Male Sprague-Dawley rats were treated ip with either 100 or 200mg/kg b.w. daily for 7 or 14 consecutive days. Controls received vehicle only. Cytochrome P450 (CYP) content, CYP-reductase, CYP-linked monooxygenases, as well as phase-II and the antioxidant enzymes catalase and NAD(P)H quinone reductase were investigated in both liver and kidney. Free radical species in tissue subcellular preparations were measured by electronic paramagnetic resonance (EPR) spectroscopy coupled to a radical probe technique. KEY FINDINGS No substantial changes of hepatic xenobiotic metabolism enzymes were determined by VE. Conversely, a powerful booster effect of various renal phase-I carcinogen bioactivating enzymes at both dosages and observational times was recorded. While no relevant changes of post-oxidative phase-II reactions were found in the liver, a significant inactivating effect was caused by VE in renal tissues. Antioxidant enzymes were found mainly downregulated by the treatment. In the kidney, a marked free radical over-generation linked to CYP induction was observed. SIGNIFICANCE This study proved that VE acts as a co-carcinogen and pro-oxidant agent. Such epigenetic mechanisms may contribute to explain the harmful outcomes observed in humans.
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Affiliation(s)
- Fabio Vivarelli
- Molecular and Toxicology Unit, Department of Pharmacy and Biotechnology, Alma-Mater Studiorum, University of Bologna, via Irnerio 48, 40126 Bologna, Italy.
| | - Donatella Canistro
- Molecular and Toxicology Unit, Department of Pharmacy and Biotechnology, Alma-Mater Studiorum, University of Bologna, via Irnerio 48, 40126 Bologna, Italy.
| | - Paola Franchi
- Department of Chemistry "G. Ciamician", Alma-Mater Studiorum, University of Bologna, Via Selmi 2, 40126 Bologna, Italy
| | - Andrea Sapone
- Molecular and Toxicology Unit, Department of Pharmacy and Biotechnology, Alma-Mater Studiorum, University of Bologna, via Irnerio 48, 40126 Bologna, Italy
| | - Andrea Vornoli
- Institute of Clinical Physiology, CNR, via Moruzzi 1, 56124 Pisa, Italy
| | - Clara Della Croce
- Institute of Agricultural Biology and Biotechnology, CNR, via Moruzzi 1, 56124 Pisa, Italy
| | - Vincenzo Longo
- Institute of Agricultural Biology and Biotechnology, CNR, via Moruzzi 1, 56124 Pisa, Italy
| | - Marco Lucarini
- Department of Chemistry "G. Ciamician", Alma-Mater Studiorum, University of Bologna, Via Selmi 2, 40126 Bologna, Italy
| | - Moreno Paolini
- Molecular and Toxicology Unit, Department of Pharmacy and Biotechnology, Alma-Mater Studiorum, University of Bologna, via Irnerio 48, 40126 Bologna, Italy
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19
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The synergistic effect between the Mediterranean diet and GSTP1 or NAT2 SNPs decreases breast cancer risk in Greek-Cypriot women. Eur J Nutr 2015; 56:545-555. [PMID: 26572891 DOI: 10.1007/s00394-015-1099-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Accepted: 11/04/2015] [Indexed: 01/06/2023]
Abstract
PURPOSE Xenobiotic metabolism is related to the interplay between diet and breast cancer (BC) risk. This involves detoxification enzymes, which are polymorphic and metabolise various dietary metabolites. An important characteristic of this pathway is that chemoprotective micronutrients can act not only as substrates but also as inducers for these enzymes. We investigated whether functional GSTP1 (p.Ile105Val-rs1695), NAT2 (590G>A-rs1799930) SNPs and GSTM1 and GSTT1 deletion polymorphisms could modulate the effect of the Mediterranean diet (MD) on BC risk, in Greek-Cypriot women. METHODS Genotyping was performed on women from the MASTOS case-control study of BC in Cyprus. A 32-item food-frequency questionnaire was used to obtain dietary intake information. A dietary pattern, which closely resembles the MD (high loadings of vegetables, fruit, legumes and fish), was previously derived with principal component analysis and was used as our dietary variable. RESULTS GSTT1 null genotype increased BC risk compared with the homozygous non-null GSTT1 genotype (OR 1.21, 95 % CI 1.01-1.45). Increasing adherence to the MD reduced BC risk in women with at least one GSTP1 Ile allele (OR for Ile/Ile = 0.84, 95 % CI 0.74-0.95, for Ile/Val = 0.73, 95 % CI 0.62-0.85) or one NAT2 590G allele (OR for 590 GG = 0.73, 95 % CI 0.63-0.83, for 590 GA = 0.81, 95 % CI 0.70-0.94). p interaction values were not, however, statistically significant. CONCLUSION The homozygous null GSTT1 genotype could be a risk allele for BC among Greek-Cypriot women. The anticarcinogenic effects of the high adherence to MD against BC risk could also be further enhanced when combined with the wild-type alleles of the detoxification GSTP1 or NAT2 SNPs.
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20
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Wang Z, Qu K, Niu W, Lin T, Xu X, Huang Z, Liu S, Liu S, Chang H, Liu Y, Dong X, Liu C, Zhang Y. Glutathione S-transferase P1 gene rs4147581 polymorphism predicts overall survival of patients with hepatocellular carcinoma: evidence from an enlarged study. Tumour Biol 2015; 37:943-52. [PMID: 26260272 DOI: 10.1007/s13277-015-3871-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2015] [Accepted: 07/30/2015] [Indexed: 02/07/2023] Open
Abstract
As the most important detoxifying enzymes in liver, glutathione S-transferases (GSTs) can protect hepatocytes against carcinogens. We conducted a large cohort study to investigate the prognostic value of single nucleotide polymorphisms (SNPs) in seven encoding genes of GSTs for hepatocellular carcinoma (HCC). Twelve SNPs were genotyped and correlated with overall survival in 469 HCC patients. The median follow-up time of all patients was 21 (range 3-60) months, and the median survival time was 22 months. By the end of the study, 135 (28.8 %) patients were alive. Only rs4147581 in GSTP1 gene exhibited a significant association with survival of HCC patients (P = 0.006), with its mutant allele bearing a significantly lower risk of death (hazard ratio, 0.71; 95 % confidence interval 0.53-0.90), compared with the homozygous wide-type. A longer median survival time in patients with rs4147581 mutant allele was noticed than those homozygous wide-type (P = 0.03), and there was a marked adverse effect on survival conferred by smoking exposure in these patients. Conclusively, our findings provide supporting evidence for a contributory role of GSTP1 rs4147581 polymorphism in predicting the prognosis of HCC.
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Affiliation(s)
- Zhixin Wang
- Department of Imaging, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China.,Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China
| | - Kai Qu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China
| | - Wenquan Niu
- State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Ruijin Second Road 197, New Huangpu District, Shanghai, 200025, China.
| | - Ting Lin
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China
| | - Xinsen Xu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China
| | - Zichao Huang
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China
| | - Sushun Liu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China
| | - Sinan Liu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China
| | - Hulin Chang
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China
| | - Yamin Liu
- Department of Cardiology and Periphery Vascular Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China
| | - Xiaoqun Dong
- Department of Internal Medicine, College of Medicine, The University of Oklahoma Health Sciences Center, 975 NE 10th Street, Biomedical Research Center BRC1366, Oklahoma, OK, 73104, USA.
| | - Chang Liu
- Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China
| | - Yuelang Zhang
- Department of Imaging, the First Affiliated Hospital of Xi'an Jiaotong University, West Yanta Road 277, Xi'an, 710061, Shaanxi, China.
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Qu K, Liu SS, Wang ZX, Huang ZC, Liu SN, Chang HL, Xu XS, Lin T, Dong YF, Liu C. Polymorphisms of glutathione S-transferase genes and survival of resected hepatocellular carcinoma patients. World J Gastroenterol 2015; 21:4310-4322. [PMID: 25892883 PMCID: PMC4394094 DOI: 10.3748/wjg.v21.i14.4310] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2014] [Revised: 08/19/2014] [Accepted: 10/21/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effects of single nucleotide polymorphisms (SNPs) in glutathione S-transferase (GST) genes on survival of hepatocellular carcinoma (HCC) patients.
METHODS: Twelve tagging SNPs in GST genes (including GSTA1, GSTA4, GSTM2, GSTM3, GSTO1, GSTO2 and GSTP1) were genotyped using Sequenom MassARRAY iPLEX genotyping method in a cohort of 214 Chinese patients with resected HCC. The Cox proportional hazards model and log-rank test were performed to determine the SNPs related to outcome. Additionally, stratified analysis was performed at each level of the demographic and clinical variables. An SNP-gene expression association model was further established to investigate the correlation between SNP and gene expression.
RESULTS: Two SNPs (GSTO2: rs7085725 and GSTP1: rs4147581) were significantly associated with overall survival in HCC patients (P = 0.035 and 0.042, respectively). In stratified analysis, they were more significantly associated with overall survival in patients with younger age, male gender and cirrhosis. We further investigated cumulative effects of these two SNPs on overall survival in HCC patients. Compared with the patients carrying no unfavorable genotypes, those carrying 2 unfavorable genotypes had a 1.70-fold increased risk of death (P < 0.001). The cumulative effects were more significant in those patients with younger age, male gender and cirrhosis (HR = 2.00, 1.94 and 1.97, respectively; all P < 0.001). Additionally, we found that heavy smoking resulted in a significantly worse overall survival in those patients carrying variant alleles of rs7085725 (HR = 2.07, 95%CI: 1.13-3.76, P = 0.018). The distributions of GSTO2: rs7085725 and GSTP1: rs4147581 genotypes were associated with altered gene expression and contributed to influences on overall survival.
CONCLUSION: Our study provides the first evidence that GSTO2 and GSTP1 gene polymorphisms may serve as independent prognostic markers for HCC patients.
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Så RAD, Moreira ADS, Cabello PH, Ornellas AA, Costa EB, Matos CDS, Alves G, Hatagima A. Human glutathione S-transferase polymorphisms associated with prostate cancer in the Brazilian population. Int Braz J Urol 2015; 40:463-73. [PMID: 25251951 DOI: 10.1590/s1677-5538.ibju.2014.04.04] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2013] [Accepted: 03/22/2014] [Indexed: 11/22/2022] Open
Abstract
OBJECTIVE To evaluate the influence of polymorphisms in GSTA1, GSTM1, GSTT1, and GSTP1 in the risk of developing Prostate Cancer (PCa) in a population of Rio de Janeiro and compare the distribution of allele and genotype frequencies of the polymorphisms analyzed in the present study population with other regions in the country and different ethnic groups. MATERIALS AND METHODS We analyzed a sample of the Brazilian population, comprising 196 patients with PCa treated by the urology services of the Brazilian National Cancer Institute (INCA) and Mario Kroeff Hospital (HMK), and 208 male blood donors from the Clementino Fraga Filho Hospital, Federal University of Rio de Janeiro (UFRJ). The polymorphisms were determined in DNA, extracted from peripheral blood leucocytes using the Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP). RESULTS Our results showed that the distribution of polymorphisms can vary significantly according to the Brazilian region and ethnic groups. The distribution of allele and genotype frequencies of the polymorphism GSTA1 was statistically different between cases and controls. Genotypes (A / B + B / B) were associated with protection (OR = 0.61, 95% CI = 0.40-0.92) for PCa in comparison to genotype A / A. CONCLUSION The distribution of genotype frequencies of the polymorphism GSTA1 was statistically different between the case and control groups (p = 0.023), and the presence of genotypes A / B and B / B suggests a protective role against the risk of PCa compared to genotype A / A. This is the first study that reports the genotypic frequency of this polymorphism and its association with PCa in a Brazilian population sample.
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Affiliation(s)
- Renata Almeida de Så
- Laboratory of Human Genetics and Laboratory of Functional Genomics and Bioinformatics, Oswaldo Cruz Institute / Oswaldo Cruz Foundation; Laboratory of Applied Genetics, Hematology Service, Rio de Janeiro, RJ, Brazil
| | - Aline Dos Santos Moreira
- Laboratory of Functional Genomics and Bioinformatics, Oswaldo Cruz Institute / Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil
| | - Pedro Hernan Cabello
- Laboratory of Human Genetics Oswaldo Cruz Institute / Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil and Brazilian National Institute of Cancer; Laboratory of Human Genetics, Grande Rio University (UNIGRANRIO), Rio de Janeiro, RJ, Brazil
| | - Antonio Augusto Ornellas
- Urology Service of Brazilian National Institute of Cancer, Rio de Janeiro, RJ, Brazil and Mário Kroeff Hospital, Rio de Janeiro, RJ, Brazil
| | - Eduardo Butinhão Costa
- Laboratory of Human Genetics, Oswaldo Cruz Institute / Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil
| | - Cintia da Silva Matos
- Laboratory of Applied Genetics, Hematology Service Brazilian National Institute of Cancer, Rio de Janeiro, RJ, Brazil and Laboratory of Clinical Pathology, Brazilian National Institute of Cancer, Rio de Janeiro, RJ, Brazil
| | - Gilda Alves
- Laboratory of Applied Genetics, Hematology Service Brazilian National Institute of Cancer, Rio de Janeiro, RJ, Brazil
| | - Ana Hatagima
- Laboratory of Human Genetics, Oswaldo Cruz Institute / Oswaldo Cruz Foundation, Rio de Janeiro, RJ, Brazil
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Eroğlu P, Erkol İnal E, Sağ ŞÖ, Görükmez Ö, Topak A, Yakut T. Associations analysis of GSTM1, T1 and P1 Ile105Val polymorphisms with carpal tunnel syndrome. Clin Rheumatol 2015; 35:1245-51. [DOI: 10.1007/s10067-014-2855-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2014] [Revised: 12/14/2014] [Accepted: 12/16/2014] [Indexed: 12/20/2022]
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Scoccianti C, Lauby-Secretan B, Bello PY, Chajes V, Romieu I. Female breast cancer and alcohol consumption: a review of the literature. Am J Prev Med 2014; 46:S16-25. [PMID: 24512927 DOI: 10.1016/j.amepre.2013.10.031] [Citation(s) in RCA: 85] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2013] [Revised: 10/29/2013] [Accepted: 10/29/2013] [Indexed: 10/25/2022]
Abstract
CONTEXT Consumption of alcoholic beverages is one of the single most important known and modifiable risk factor for human cancer. Among women, breast cancer is the most common cancer worldwide and the leading cause of cancer-related mortality. Consumption of alcoholic beverages is causally associated with female breast cancer and the association shows a linear dose-response relationship. The role of heavy drinking has been long recognized and even a moderate intake is associated with an increased risk for breast cancer. The present review is an update of the current evidence on the association between alcohol consumption and breast cancer risk. The aim is to gain further insight into this association and to improve our current understanding of the effects of the major modifying factors. EVIDENCE ACQUISITION Epidemiologic and experimental studies published since the most recent International Agency for Research on Cancer (IARC) Monograph on alcoholic beverages were identified in PubMed using a combination of keywords such as alcohol, breast cancer, polymorphisms, menopausal status. EVIDENCE SYNTHESIS Cumulative lifetime consumption, drinking frequency, drinking patterns and timing of exposure each modulate the association between alcohol consumption and breast cancer. Hormonal status, genetic polymorphisms, and nutritional factors may interact with ethanol metabolism and further influence breast cancer risk. CONCLUSIONS Better standardization among experimental and epidemiologic designs in assessing alcohol intake and timing of exposure may improve our understanding of the heterogeneity observed across studies, possibly allowing the quantification of the effects of occasional heavy drinking and the identification of a window of higher susceptibility to breast cancer development.
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Affiliation(s)
- Chiara Scoccianti
- Nutritional Epidemiology Group, International Agency for Research on Cancer, Lyon
| | | | | | - Véronique Chajes
- Nutritional Epidemiology Group, International Agency for Research on Cancer, Lyon
| | - Isabelle Romieu
- Nutritional Epidemiology Group, International Agency for Research on Cancer, Lyon.
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25
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Dhaini HR, Kobeissi L. Toxicogenetic profile and cancer risk in Lebanese. JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH. PART B, CRITICAL REVIEWS 2014; 17:95-125. [PMID: 24627976 DOI: 10.1080/10937404.2013.878679] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
An increasing number of genetic polymorphisms in drug-metabolizing enzymes (DME) were identified among different ethnic groups. Some of these polymorphisms are associated with an increased cancer risk, while others remain equivocal. However, there is sufficient evidence that these associations become significant in populations overexposed to environmental carcinogens. Hence, genetic differences in expression activity of both Phase I and Phase II enzymes may affect cancer risk in exposed populations. In Lebanon, there has been a marked rise in reported cancer incidence since the 1990s. There are also indicators of exposure to unusually high levels of environmental pollutants and carcinogens in the country. This review considers this high cancer incidence by exploring a potential gene-environment model based on available DME polymorphism prevalence, and their impact on bladder, colorectal, prostate, breast, and lung cancer in the Lebanese population. The examined DME include glutathione S-transferases (GST), N-acetyltransferases (NAT), and cytochromes P-450 (CYP). Data suggest that these DME influence bladder cancer risk in the Lebanese population. Evidence indicates that identification of a gene-environment interaction model may help in defining future research priorities and preventive cancer control strategies in this country, particularly for breast and lung cancer.
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Affiliation(s)
- Hassan R Dhaini
- a Faculty of Health Sciences , University of Balamand , Beirut , Lebanon
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26
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Sergentanis TN, Diamantaras AA, Perlepe C, Kanavidis P, Skalkidou A, Petridou ET. IVF and breast cancer: a systematic review and meta-analysis. Hum Reprod Update 2013; 20:106-23. [PMID: 23884897 DOI: 10.1093/humupd/dmt034] [Citation(s) in RCA: 67] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The effects of controlled ovarian hyperstimulation (COH) for IVF in terms of breast cancer risk remain controversial, despite the hormone-dependent nature of the latter. METHODS Eligible studies up to 15 February 2013 were identified and pooled effect estimates for relative risk (RR) were calculated separately for the investigations using the general population and those using infertile women, as a reference group. Fixed- or random-effects models were implemented and subgroup analyses were performed, as appropriate. RESULTS Eight cohort studies were synthesized, yielding a total cohort size of 1,554,332 women among whom 14,961 incident breast cancer cases occurred, encompassing 576 incident breast cancer cases among women exposed to IVF. No significant association between IVF and breast cancer was observed either in the group of studies treating the general population (RR = 0.91, 95% confidence interval (CI): 0.74-1.11) or infertile women (RR = 1.02, 95% CI: 0.88-1.18), as a reference group. Of note were the marginal associations, protective for pregnant and/or parous women after IVF (pooled effect estimate = 0.86, 95% CI: 0.73-1.01) and adverse for women <30 years at first IVF treatment (pooled effect estimate = 1.64, 95% CI: 0.96-2.80). CONCLUSIONS At present, COH for IVF does not seem to impart increased breast cancer risk. Longer follow-up periods, comparisons versus infertile women, subgroup analyses aiming to trace vulnerable subgroups, adjustment for various confounders and larger informative data sets are needed before conclusive statements for the safety of the procedure are reached.
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Affiliation(s)
- Theodoros N Sergentanis
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School, University of Athens, 75 M. Asias Str. Goudi, Athens 115 27, Greece
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Ge J, Tian AX, Wang QS, Kong PZ, Yu Y, Li XQ, Cao XC, Feng YM. The GSTP1 105Val allele increases breast cancer risk and aggressiveness but enhances response to cyclophosphamide chemotherapy in North China. PLoS One 2013; 8:e67589. [PMID: 23826324 PMCID: PMC3691318 DOI: 10.1371/journal.pone.0067589] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2013] [Accepted: 05/20/2013] [Indexed: 12/22/2022] Open
Abstract
The glutathione-S-transferase (GST) family contributes to the inactivation of various toxic compounds formed as secondary metabolites during oxidative stress. GSTP1 accounts for the majority of the GST family enzymatic activity, and the activity of GSTP1 enzyme can be altered by the presence of the Ile105Val polymorphism. In this study, we examined the polymorphic frequency of GSTP1 Ile105Val genotype in 920 breast cancer patients and 783 healthy controls in women of North China. Results showed that GSTP1 105Val allele (Ile/Val and Val/Val) was associated with a higher breast cancer risk (OR = 1.38, 95% CI: 1.14–1.69; P = 0.001) and more aggressive tumors with histological grade III (OR = 1.15, 95% CI: 1.05–1.26; P = 0.001), lymph node metastases (OR = 2.35, 95% CI: 1.72–3.21; P < 0.001), as well as ER negative (OR = 1.77, 95% CI: 1.31–2.39; P < 0.001) than those carrying the Ile/Ile allele. However, the patients with the GSTP1 105Val genotype had a better disease free survival after cyclophosphamide (CTX)-based chemotherapy than those with Ile/Ile (HR = 0.77, 95% CI: 0.45–0.91; P < 0.001). Furthermore, in vitro cellular experiments demonstrated that breast cancer cells with the GSTP1 105Val allele were significantly more sensitive to CTX-induced proliferation inhibition. Thus, we conclude that the GSTP1 105Val allele increases breast cancer risk and aggressiveness and enhance response to CTX-based chemotherapy in women of North China. Detection of the GSTP1 Ile105Val genotype may help screen for high-risk populations and direct individualized therapy.
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Affiliation(s)
- Jie Ge
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
- Department of Breast surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
- Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Ai-Xian Tian
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Qing-Shan Wang
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
- Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Peng-Zhou Kong
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Yue Yu
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Xiao-Qing Li
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
- Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Xu-Chen Cao
- Department of Breast surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
- Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Yu-Mei Feng
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
- Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
- * E-mail:
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Yang X, Long S, Deng J, Deng T, Gong Z, Hao P. Glutathione S-transferase polymorphisms (GSTM1, GSTT1 and GSTP1) and their susceptibility to renal cell carcinoma: an evidence-based meta-analysis. PLoS One 2013; 8:e63827. [PMID: 23717494 PMCID: PMC3661732 DOI: 10.1371/journal.pone.0063827] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2013] [Accepted: 04/05/2013] [Indexed: 02/05/2023] Open
Abstract
Background The association of the three Glutathione S-transferases (GSTs) polymorphisms (GSTM1, GSTT1 and GSTP1) genotypes with their individual susceptibilities to renal cell carcinoma (RCC) has not been well established. We performed a quantitative meta-analysis to assess the possible associations between the GSTM1, GSTT1 and GSTP1 genotypes and their individual susceptibilities to renal cell carcinoma. Methods We systematically searched the PubMed, CNKI and Embase databases to identify the relevant studies. Finally, 11 eligible studies were selected. The pooled odds ratios (ORs) with their 95% confidence intervals (CIs) were used to assess the association between the GSTs polymorphisms and the risk of RCC. Multiple subgroup analyses and quality assessment of the included studies were performed based on the available information. Results None of the GSTs polymorphisms had a significant association with the RCC risk. Similar results were found in the subgroup analyses, except for the GSTs polymorphisms in the situations described below. The GSTM1 and GSTT1 active genotypes in subjects exposed to pesticides (GSTM1: OR = 3.44; 95% CI, 2.04–5.80; GSTT1: OR = 2.84; 95% CI, 1.75–4.60), most of the GSTs genotypes in Asian populations (GSTT1: OR = 2.39, 95% CI = 1.63–3.51; GSTP1: Dominant model: OR = 1.50, 95% CI = 1.14–1.99; Additive model: OR = 1.39, 95% CI = 1.12–1.73; AG vs. AA: OR = 1.47, 95% CI = 1.10–1.97; GG vs. AA: OR = 1.82, 95% CI = 1.07–3.09) and the dual null genotype of GSTT1-GSTP1 (OR = 2.84, 95% CI = 1.75–4.60) showed positive associations with the RCC risk. Conclusion Our present study provides evidence that the GSTM1, GSTT1 and GSTP1 polymorphisms are not associated with the development of RCC. However, more case-control studies are needed for further confirmation.
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Affiliation(s)
- Xingliang Yang
- Department of Urology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Shuyu Long
- Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jianping Deng
- Department of Urology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Tianxing Deng
- Department of Urology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Zhihua Gong
- Department of Oncology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
| | - Ping Hao
- Department of Oncology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
- * E-mail:
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29
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Zgheib NK, Shamseddine AA, Geryess E, Tfayli A, Bazarbachi A, Salem Z, Shamseddine A, Taher A, El-Saghir NS. Genetic polymorphisms of CYP2E1, GST, and NAT2 enzymes are not associated with risk of breast cancer in a sample of Lebanese women. Mutat Res 2013; 747-748:40-7. [PMID: 23628324 DOI: 10.1016/j.mrfmmm.2013.04.004] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2012] [Revised: 03/25/2013] [Accepted: 04/19/2013] [Indexed: 11/28/2022]
Abstract
Changes in the activity of drug metabolizing enzymes (DMEs) are potentially associated with cancer risk. This relationship is attributed to their involvement in the bioactivation of multiple procarcinogens or the metabolism of multiple substrates including an array of xenobiotics and environmental carcinogens. 326 Lebanese women of whom 99 were cancer free (controls) and 227 were diagnosed with breast cancer (cases) were included. Blood for DNA was collected and medical charts were reviewed. Three genotyping methods were employed including: (1) restriction fragment length polymorphism (RFLP) for CYP2E1*5B, CYP2E1*6, NAT2*5 and NAT2*6; (2) gel electrophoresis for GSTM1 and GSTT1; and (3) real-time PCR for GSTP1 Ile/Val polymorphism. We analyzed the relationship between genetic susceptibilities in selected xenobiotic metabolizing genes and breast cancer risk. Allele frequencies were fairly similar to previously reported values from neighboring populations with relevant migration routes. There were no statistically significant differences in the distribution of variant carcinogen metabolizing genes between cases and controls even after adjusting for age at diagnosis, menopausal status, smoking, and alcohol intake. Despite its limitations, this is the first study that assesses the role of genetic polymorphisms in DMEs with breast cancer in a sample of Lebanese women. Further studies are needed to determine the genetic predisposition and gene-environment interactions of breast cancer in this population.
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Affiliation(s)
- Nathalie K Zgheib
- Department of Pharmacology & Toxicology, Faculty of Medicine, American University of Beirut, Lebanon.
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30
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Huang SX, Wu FX, Luo M, Ma L, Gao KF, Li J, Wu WJ, Huang S, Yang Q, Liu K, Zhao YN, Li LQ. The glutathione S-transferase P1 341C>T polymorphism and cancer risk: a meta-analysis of 28 case-control studies. PLoS One 2013; 8:e56722. [PMID: 23437223 PMCID: PMC3578943 DOI: 10.1371/journal.pone.0056722] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2012] [Accepted: 01/14/2013] [Indexed: 01/01/2023] Open
Abstract
Background GSTP1, which is one major group of the glutathione S-transferase family, plays an important role in the metabolism of carcinogens and toxins, reducing damage of DNA as a suppressor of carcinogenesis. The 341C>T polymorphism of the GSTP1 has been implicated in cancer risk through cutting down its metabolic detoxification activities. However, results from previous studies remain conflicting rather than conclusive. To clarify the correlation and provide more statistical evidence for detecting the significance of 341C>T, a meta-analysis was conducted. Methodology/Principal Findings The relevant studies were identified through searching of PubMed, Embase, ISI Web of Knowledge and China National Knowledge Infrastructure in August 2012, and selected based on the established inclusion criteria for publications, then a meta-analysis was performed to quantitatively summarize the association of GSTP1 341C>T polymorphism with cancer susceptibility. Stratified analyses were employed to identify the source of heterogeneity. Publication bias was evaluated as well as sensitivity analysis. Based on 28 case-control studies with 13249 cases and 16798 controls, the pooled results indicated that the variant genotypes significantly increased the risk of cancer in homozygote comparison (TT versus CC: P = 0.012, OR = 1.40, 95% CI: 1.08–1.81, Phet. = 0.575), and recessive model (TT versus CT/CC: P = 0.012, OR = 1.40, 95% CI: 1.08–1.81, Phet. = 0.562). This was confirmed when stratified analyses were conducted according to ethnicity, source of control, matched control, quality score and cancer types. Moreover, significantly increased risk of cancer was also found in lung cancer (heterozygote comparison and dominant model). The stability of these observations was confirmed by a sensitivity analysis. Begger's funnel plot and Egger's test did not reveal any publication bias. Conclusions/Significance This meta-analysis suggests that the GSTP1 341C>T polymorphism may contribute to genetic susceptibility to cancer, especially to lung cancer, and in Asian population. Nevertheless, additional well-designed studies focusing on different ethnicity and cancer types are needed to provide a more exact and comprehensive conclusion.
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Affiliation(s)
- Sheng-xin Huang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Fei-xiang Wu
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Min Luo
- Department of Experiment, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Liang Ma
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Ke-feng Gao
- Department of Thoracic Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Jian Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Wen-juan Wu
- Department of Gynecologic Oncology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Shan Huang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Qi Yang
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Ke Liu
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Yin-nong Zhao
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China
| | - Le-qun Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China
- * E-mail:
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A meta-analysis of the association of glutathione S-transferase P1 gene polymorphism with the susceptibility of breast cancer. Mol Biol Rep 2013; 40:3203-12. [PMID: 23334471 DOI: 10.1007/s11033-012-2396-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2012] [Accepted: 12/17/2012] [Indexed: 12/28/2022]
Abstract
Glutathione S-transferase P1 (GSTP1) is one of the important mutant sites for the cancer risk at present. The conclusions of the published reports on the relationship between GSTP1 A/G gene polymorphism and the risk of breast cancer are still debated. This meta-analysis was performed to evaluate the association between GSTP1 and the risk of breast cancer. The association reports were identified from PubMed and Cochrane Library, and eligible studies were included and synthesized using meta-analysis method. 35 investigations were included into this meta-analysis for the association of GSTP1 A/G gene polymorphism and breast cancer susceptibility, consisting of 40,347 subjects (18,665 patients with breast cancer and 21,682 controls). The association between GSTP1 A/G gene polymorphism and breast cancer risk was not found for overall population, Caucasians and Africans. Interestingly, the GSTP1 A/G gene polymorphism was associated with the susceptibility of breast cancer in Asians (G allele: OR = 1.10, 95 % CI: 1.04-1.17, P = 0.001; GG genotype: OR = 1.36, 95 % CI: 1.14-1.62, P = 0.0008; AA genotype: OR = 0.92, 95 % CI: 0.85-0.98, P = 0.02). Furthermore, the GSTP1 A/G gene polymorphism was associated with the susceptibility of breast cancer for the analysis of the controls from hospital. In conclusion, GSTP1 A/G gene polymorphism is associated with the breast cancer susceptibility in Asians. However, more studies on the relationship between GSTP1 A/G gene polymorphism and the risk of breast cancer should be performed in further.
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Hashemi M, Eskandari-Nasab E, Fazaeli A, Taheri M, Rezaei H, Mashhadi M, Arbabi F, Kaykhaei MA, Jahantigh M, Bahari G. Association Between Polymorphisms of Glutathione
S-
Transferase Genes (
GSTM1
,
GSTP1
and
GSTT1
) and Breast Cancer Risk in a Sample Iranian Population. Biomark Med 2012; 6:797-803. [DOI: 10.2217/bmm.12.61] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Affiliation(s)
- Mohammad Hashemi
- Cellular & Molecular Research Center,Zahedan University of Medical Sciences,
Zahedan,
Iran
- Department of Clinical Biochemistry,School of Medicine,Zahedan University of Medical Sciences,
Zahedan,
Iran
| | - Ebrahim Eskandari-Nasab
- Department of Clinical Biochemistry,School of Medicine,Zahedan University of Medical Sciences,
Zahedan,
Iran
| | - Aliakbar Fazaeli
- Department of Clinical Biochemistry,School of Medicine,Zahedan University of Medical Sciences,
Zahedan,
Iran
| | - Mohsen Taheri
- Genetic of Non-Communicable Disease Research Center,Zahedan University of Medical Sciences,
Zahedan,
Iran
| | - Hamzeh Rezaei
- Department of Clinical Biochemistry,School of Medicine,Zahedan University of Medical Sciences,
Zahedan,
Iran
| | - Mohammadali Mashhadi
- Department of Internal Medicine,School of Medicine,Zahedan University of Medical Sciences,
Zahedan,
Iran
| | - Farshid Arbabi
- Brain & Spinal Injury Research Center,Tehran University of Medical Sciences,
Tehran,
Iran
| | - Mahmoud-Ali Kaykhaei
- Department of Internal Medicine,School of Medicine,Zahedan University of Medical Sciences,
Zahedan,
Iran
| | - Mehdi Jahantigh
- Department of Pathology, School of Medicine,Zahedan University of Medical Sciences,
Zahedan,
Iran
| | - Gholamreza Bahari
- Department of Clinical Biochemistry,School of Medicine,Zahedan University of Medical Sciences,
Zahedan,
Iran
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Ruiz JR, Fiuza-Luces C, Buxens A, Cano-Nieto A, Gómez-Gallego F, Santiago C, Rodríguez-Romo G, Garatachea N, Lao JI, Morán M, Lucia A. Are centenarians genetically predisposed to lower disease risk? AGE (DORDRECHT, NETHERLANDS) 2012; 34:1269-1283. [PMID: 21894447 PMCID: PMC3448993 DOI: 10.1007/s11357-011-9296-3] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/04/2011] [Accepted: 07/25/2011] [Indexed: 05/31/2023]
Abstract
Our study purpose was to compare a disease-related polygenic profile that combined a total of 62 genetic variants among (i) people reaching exceptional longevity, i.e., centenarians (n = 54, 100-108 years, 48 women) and (ii) ethnically matched healthy controls (n = 87, 19-43 years, 47 women). We computed a 'global' genotype score (GS) for 62 genetic variants (mutations/polymorphisms) related to cardiometabolic diseases, cancer or exceptional longevity, and also specific GS for main disease categories (cardiometabolic risk and cancer risk, including 36 and 24 genetic variations, respectively) and for exceptional longevity (7 genetic variants). The 'global' GS was similar among groups (centenarians: 31.0 ± 0.6; controls 32.0 ± 0.5, P = 0.263). We observed that the GS for hypertension, cancer (global risk), and other types of cancer was lower in the centenarians group compared with the control group (all P < 0.05), yet the difference became non significant after adjusting for sex. We observed significant between-group differences in the frequency of GSTT1 and GSTM1 (presence/absence) genotypes after adjusting for multiple comparisons. The likelihood of having the GSTT1 low-risk (functional) allele was higher in centenarians (odds ratio [OR] 5.005; 95% confidence interval [CI], 1.810-13.839), whereas the likelihood of having the GSTMI low-risk (functional) allele was similar in both groups (OR 1.295; 95% CI, 0.868 -1.931). In conclusion, we found preliminary evidence that Spanish centenarians have a lower genetic predisposition for cancer risk. The wild-type (i.e., functional) genotype of GSTT1, which is associated with lower cancer risk, might be associated with exceptional longevity, yet further studies with larger sample sizes must confirm these findings.
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Affiliation(s)
- Jonatan R Ruiz
- Department of Physical Education and Sport, School of Physical Activity and Sport Sciences, University of Granada, Granada, Spain.
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34
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Non-random distribution of breast cancer susceptibility loci on human chromosomes. Breast Cancer Res Treat 2012; 136:315-8. [PMID: 22910932 DOI: 10.1007/s10549-012-2208-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2012] [Accepted: 08/10/2012] [Indexed: 01/23/2023]
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35
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Sergentanis TN, Economopoulos KP, Choussein S, Vlahos NF. Cytochrome P450 1A1 (CYP1A1) gene polymorphisms and cervical cancer risk: a meta-analysis. Mol Biol Rep 2012; 39:6647-54. [PMID: 22294106 DOI: 10.1007/s11033-012-1470-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2011] [Accepted: 01/23/2012] [Indexed: 10/14/2022]
Abstract
This meta-analysis aims to examine whether the genotype status of MspI and Ile462Val polymorphisms in Cytochrome-P450 1A1 (CYP1A1) is associated with cervical cancer risk. Eligible case-control studies were identified through search in MEDLINE (end of search: October 2010). Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random effects models. Concerning MspI polymorphism, six studies were eligible (722 cases and 770 controls); four studies were eligible (350 cases and 519 controls) for Ile462Val. MspI polymorphism was associated with elevated cervical cancer risk (for heterozygous TC vs. TT carriers OR = 1.50, 95% CI: 0.93-2.42, random effects; for homozygous CC vs. TT carriers OR = 2.66, 95% CI: 1.14-6.19, random effects). Similarly, Ile462Val polymorphism was associated with elevated cervical cancer risk (for heterozygous Ile/Val vs. Ile/Ile carriers OR = 2.36, 95% CI: 1.10-5.08, random effects; for homozygous Val/Val vs. Ile/Ile carriers OR = 2.73, 95% CI: 1.21-6.15, fixed effects). The results were replicated upon Caucasian subjects, who represented the majority of existing data. The two examined CYP1A1 genotype polymorphisms seem to confer additional risk for cervical cancer. Accumulation of further data seems mandatory for future race-specific analyses and for the demonstration of CYP1A1-smoking interactions.
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36
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Li J, Long J, Hu Y, Tan A, Guo X, Zhang S. Glutathione S-transferase M1, T1, and P1 polymorphisms and thyroid cancer risk: a meta-analysis. Cancer Epidemiol 2012; 36:e333-40. [PMID: 22765906 DOI: 10.1016/j.canep.2012.06.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2012] [Revised: 06/04/2012] [Accepted: 06/05/2012] [Indexed: 02/07/2023]
Abstract
Glutathione S-transferases (GSTs) genetic variants have been explored extensively as a predictive factor for cancer etiology. This meta-analysis aimed to examine the associations GSTM1, GSTT1, and GSTP1 genetic polymorphisms with thyroid cancer risk. PubMed, EMBASE, Cochrane Library, and HuGNet database were searched up to November 2011 using the appropriate terms. Twelve studies regarding GSTM1 null polymorphism (1569 cases and 2907 controls), 11 studies concerning GSTT1 null polymorphism (1515 cases and 2863 controls), and 8 studies on GSTP1 Ile105Val (965 cases and 1604 controls) were included in the meta-analysis. The random effects odds ratio was 1.07 (95% CI: 0.88-1.31; I(2) = 54.1%, P for heterogeneity = 0.013) for the GSTM1 null vs. present genotype and 1.08 (95% CI: 0.75-1.57; I(2) = 81.4%, P for heterogeneity < 0.001) for the GSTT1 null vs. present genotype, and 1.02 (95% CI: 0.70-1.49; I(2) = 74.6%, P for heterogeneity < 0.001) for the GSTP1 Val/Val+Val/Ile vs. Ile/Ile genotype. Similarly, no significant associations were demonstrated for subgroup analyses performed by ethnicity and histological type. In conclusion, these three polymorphisms are unlikely to be major determinants of susceptibility to thyroid cancer. Reasons for potential heterogeneity of effects, which could include true biologic heterogeneity, publication bias, or chance, deserve further investigation. The relationship between these three genes and thyroid carcinoma must be evaluated further with gene-gene and gene-environment interactions.
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Affiliation(s)
- Jianling Li
- Institute of Cardiovascular Disease, First Affiliated Hospital of Guangxi Medical University, Nanning, China
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37
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Cytochrome P450 1A1 (CYP1A1) gene polymorphisms and ovarian cancer risk: a meta-analysis. Mol Biol Rep 2012; 39:9921-30. [DOI: 10.1007/s11033-012-1860-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2010] [Accepted: 01/17/2012] [Indexed: 10/28/2022]
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38
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Xu Z, Zhu H, Luk JM, Wu D, Gu D, Gong W, Tan Y, Zhou J, Tang J, Zhang Z, Wang M, Chen J. Clinical significance of SOD2 and GSTP1 gene polymorphisms in Chinese patients with gastric cancer. Cancer 2012; 118:5489-96. [PMID: 22517484 DOI: 10.1002/cncr.27599] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2011] [Revised: 03/13/2012] [Accepted: 03/19/2012] [Indexed: 12/16/2022]
Abstract
BACKGROUND Excessive reactive oxygen species (ROS) accumulation is a common phenomenon in carcinogenesis. However, the rationale behind ROS involvement in gastric cancer is unclear. In this study, the authors investigated the clinical significance of the single nucleotide polymorphisms (SNPs) of 2 ROS metabolic process-related genes: superoxide dismutase 2 (SOD2) and glutathione S-transferase π (GSTP1). METHODS In total of 929 patients with gastric cancer who had definitive clinicopathologic and follow-up data were collected. SOD2 reference SNP 4880 (rs4880) and GSTP1 rs1695 genotyping were examined in DNA samples extracted from paraffin-embedded tumor tissue. Association of the 2 SNPs with each clinicopathologic feature was analyzed using the Pearson chi-square test and the independent Student t test. Gastric cancer-specific overall survival was analyzed using Kaplan-Meier curves and log-rank tests. Multivariate Cox regression analyses of these SNPs also were performed. RESULTS The SOD2 rs4880 CT + CC genotypes were significantly associated with a high level of lymph node metastasis (P = .023), whereas the GSTP1 rs1695 GA + GG genotypes were significantly associated with larger tumor size (>5 cm long; P = .048). Kaplan-Meier and Cox regression data indicated that the SOD2 rs4880 CT + CC genotypes alone (hazard ratio, 1.299; 95% confidence interval, 1.053-1.603; P = .015) and the GSTP1 rs1695 GA + GG combined genotypes (hazard ratio, 1.496; 95% CI, 1.078-2.074; P = .016) were independent predictors for overall survival. CONCLUSIONS The current data, based on a large cohort (n = 929) of Chinese patients with gastric cancer, suggested that the presence of SOD2 rs4880 and GSTP1 rs1695 genotypes may contribute to cancer progression as well as tumor aggressiveness. The components of ROS metabolism pathways may be potential therapeutic targets for this aggressive malignancy.
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Affiliation(s)
- Zhi Xu
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
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39
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Jaiswal D, Sah R, Agrawal NK, Dwivedi US, Trivedi S, Singh K. Combined Effect of GSTT1 and GSTM1 Polymorphisms on Human Male Infertility in North Indian Population. Reprod Sci 2012; 19:312-6. [DOI: 10.1177/1933719111424451] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Affiliation(s)
- Deepika Jaiswal
- Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Ravindra Sah
- Sah Speciality Clinic, Ravindrapuri Colony, Durgakund, Varanasi, Uttar Pradesh, India
| | - Neeraj K. Agrawal
- Department of Endocrinology and Metabolism, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - U. S. Dwivedi
- Department of Urology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Sameer Trivedi
- Department of Urology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
| | - Kiran Singh
- Department of Molecular and Human Genetics, Banaras Hindu University, Varanasi, Uttar Pradesh, India
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40
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Saadat M, Khalili M, Nasiri M, Rajaei M, Omidvari S, Saadat I. Clinical response to chemotherapy in locally advanced breast cancer was not associated with several polymorphisms in detoxification enzymes and DNA repair genes. Biochem Biophys Res Commun 2012; 419:117-9. [PMID: 22330804 DOI: 10.1016/j.bbrc.2012.01.143] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2012] [Accepted: 01/28/2012] [Indexed: 01/18/2023]
Abstract
The main aim of the present study was to investigate the association between several genetic polymorphisms (in glutathione S-transferase members and DNA repair genes) and clinical response to chemotherapy in locally advanced breast cancer. A sequential series of 101 patients were prospectively included in this study. Clinical assessment of treatment was accomplished by comparing initial tumor size with preoperative tumor size using revised RECIST guideline (version 1.1). Clinical response was regarded as a response or no response. There was no difference between non-responders and responders for the prevalence of genotypes of the study polymorphisms.
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Affiliation(s)
- Mostafa Saadat
- Department of Biology, College of Sciences, Shiraz University, Shiraz 71454, Iran.
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41
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Zhong S, Yang JH, Liu K, Jiao BH, Chang Z. Null genotype of glutathione S-transferase Tl contributes to colorectal cancer risk in the Asian population: a meta-analysis. J Gastroenterol Hepatol 2012; 27:231-7. [PMID: 21916987 DOI: 10.1111/j.1440-1746.2011.06920.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
BACKGROUND AND AIM Previous studies investigating the association between the glutathione S-transferase Tl (GSTT1) null genotype and colorectal cancer (CRC) risk in the Asian population have reported controversial results. Thus, a meta-analysis was performed to clarify the effect of the GSTT1 null genotype on CRC risk in the Asian population. METHODS A comprehensive study was conducted, and 12 case-control studies were finally included, involving a total of 4517 CRC cases and 6607 controls. Subgroup analyses were performed by the sample size. RESULTS A meta-analysis of all 12 studies showed that the GSTT1 null genotype was significantly associated with an increased CRC risk in the Asian population (odds ratio [OR] = 1.10, 95% confidence interval [CI] = 1.02-1.19, the P-value of the OR [P(OR)] = 0.02, the value of the heterogeneity analysis [I(2)] = 42%). A more obvious association was observed after the heterogeneity was eliminated by excluding one study (OR = 1.15, 95% CI: 1.06-1.25, P(OR) = 0.001, I(2) = 0%). This association was further identified by both subgroup analyses and a sensitivity analysis. CONCLUSIONS This meta-analysis suggests that the GSTT1 null genotype contributes to an increased colorectal cancer risk in the Asian population.
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Affiliation(s)
- Shan Zhong
- State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing, China
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42
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Block G, Shaikh N, Jensen CD, Volberg V, Holland N. Serum vitamin C and other biomarkers differ by genotype of phase 2 enzyme genes GSTM1 and GSTT1. Am J Clin Nutr 2011; 94:929-37. [PMID: 21813807 PMCID: PMC3155929 DOI: 10.3945/ajcn.111.011460] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Glutathione S-transferases (GSTs) detoxify environmental chemicals and are involved in oxidative stress pathways. Deletion polymorphisms affect enzyme activities and have been associated with risk of disease. OBJECTIVE The objective was to clarify whether biomarkers of oxidation, antioxidation, inflammation, and nutritional factors differ by GST genotype in healthy adults. DESIGN Subjects (n = 383) consisted of nonsmokers and nonusers of antiinflammatory drugs and antioxidant vitamin supplements. Deletion polymorphisms of GSTM1 and GSTT1 were genotyped. F(2)-isoprostanes, malondialdehyde, C-reactive protein, serum vitamin C, carotenoids, tocopherols, and other nutritional factors were assessed. RESULTS The concentration of serum vitamin C was higher in persons with the inactive GSTM1-0 genotype (P = 0.006). This relation was unchanged after adjustment for age, sex, BMI, or dietary vitamin C. F(2)-isoprostanes and malondialdehyde were lower in the GSTM1-0 and GSTT1-0 groups, respectively, but significance was lost after control for serum vitamin C. The dual deletion, GSTM1-0/GSTT1-0 (n = 37), was associated with higher serum iron and total and LDL-cholesterol concentrations (all P < 0.01) and lower malondialdehyde concentrations, which persisted after adjustment for age, sex, BMI, and serum vitamin C. Carotenoids and α- and γ-tocopherols were not associated with either genotype. CONCLUSIONS Oxidative stress and inflammation biomarkers differ by GST genotype, but serum vitamin C appears to be the most consistent factor. Examination of other relevant genes may be needed to understand the concentration and function of ascorbic acid in the GST enzyme system. This trial is registered at clinicaltrials.gov as NCT00079963.
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Affiliation(s)
- Gladys Block
- School of Public Health, University of California at Berkeley, 94720-7360, USA.
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Naushad SM, Reddy CA, Rupasree Y, Pavani A, Digumarti RR, Gottumukkala SR, Kuppusamy P, Kutala VK. Cross-Talk Between One-Carbon Metabolism and Xenobiotic Metabolism: Implications on Oxidative DNA Damage and Susceptibility to Breast Cancer. Cell Biochem Biophys 2011; 61:715-23. [DOI: 10.1007/s12013-011-9245-x] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Gao LB, Pan XM, Li LJ, Liang WB, Bai P, Rao L, Su XW, Wang T, Zhou B, Wei YG, Zhang L. Null genotypes of GSTM1 and GSTT1 contribute to risk of cervical neoplasia: an evidence-based meta-analysis. PLoS One 2011; 6:e20157. [PMID: 21629772 PMCID: PMC3100325 DOI: 10.1371/journal.pone.0020157] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2010] [Accepted: 04/26/2011] [Indexed: 01/09/2023] Open
Abstract
Background and Objectives Glutathione S-transferases (GSTs) are multifunctional enzymes that play a key role in the detoxification of varieties of both endogenous products of oxidative stress and exogenous carcinogens. Methods In this meta-analysis, twenty-five studies were identified by searching PubMed, EMBASE, ISI Web of Science and CBM databases: 23 evaluated GSTM1 and 19 evaluated GSTT1. Crude odds ratios with corresponding 95% confidence intervals were used to estimate the association between GSTM1 and GSTT1 polymorphisms and risk of cervical neoplasia. Subgroup analyses were conducted by pathological history, ethnicity, source of DNA for genotyping, quality score, and matching variable. Results The null genotypes of GSTM1 and GSTT1 polymorphisms were associated with a significantly increased risk of cervical neoplasia (for GSTM1: OR = 1.40; 95%CI, 1.19–1.65; for GSTT1: OR = 1.30; 95%CI, 1.05–1.62, respectively). Subgroup analyses showed that the null genotype of GSTM1 increased the risk of cervical neoplasia in Asians, studies with DNA isolation from white blood cells and tissue samples, both high and low quality studies, and matched studies. In GSTM1-GSTT1 interaction analysis, individuals with dual null genotype were associated with a significantly increased risk of cervical neoplasia (OR = 1.72; 95%CI, 1.18–2.51). Conclusion These findings indicate that GSTM1 and GSTT1 polymorphisms, particularly GSTM1-GSTT1 interaction, may play critical roles in the development of cervical neoplasia. A conservative manner should be adopted to interpret these results because of obvious heterogeneity between-study, unadjusted data, and relatively small sample size in this meta-analysis. Well designed studies with larger sample size are of great value to confirm these results.
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Affiliation(s)
- Lin-Bo Gao
- Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Xin-Min Pan
- Department of Forensic Pathology, Henan University of Science and Technology, Luoyang, Henan, People's Republic of China
- Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Li-Juan Li
- Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Wei-Bo Liang
- Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Peng Bai
- Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Li Rao
- Department of Cardiology, West China Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Xiao-Wei Su
- Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Tao Wang
- Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Bin Zhou
- Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Yong-Gang Wei
- Department of General Surgery, West China Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Lin Zhang
- Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China
- * E-mail:
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Zhang B, Beeghly-Fadiel A, Lu W, Cai Q, Xiang YB, Zheng Y, Long J, Ye C, Gu K, Shu XO, Gao Y, Zheng W. Evaluation of functional genetic variants for breast cancer risk: results from the Shanghai breast cancer study. Am J Epidemiol 2011; 173:1159-70. [PMID: 21454829 DOI: 10.1093/aje/kwr004] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
In previous studies among 1,144 cases and 1,256 controls recruited in stage 1 of the Shanghai Breast Cancer Study (SBCS I; 1996-1998), 18 known or potentially functional single nucleotide polymorphisms (SNPs) in 16 genes were found to be associated with breast cancer risk. The authors evaluated these associations among 1,918 cases and 1,819 controls recruited in stage 2 of the SBCS (SBCS II; 2002-2005) using genetic effect models and subgroup analyses predetermined from SBCS I results. Five SNPs (AHR rs2066853, ATM rs1003623, ESR1 rs2234693, GSTP1 rs1695, and SHBG rs6259) showed generally consistent results in SBCS I and SBCS II and statistically significant associations with breast cancer risk in combined analyses, mostly in subgroups defined by age or menopausal status. Further, the relation between breast cancer risk and SHBG rs6259 was found to vary by body mass index (weight (kg)/height (m)(2)) (P for interaction = 0.003). The strongest reduction in risk associated with SHBG rs6259 was found for lean (body mass index <23) postmenopausal minor allele carriers (odds ratio = 0.6, 95% confidence interval: 0.5, 0.8; P = 4.6 × 10(-4)). This biologically plausible and highly significant finding provides strong evidence for a true association among Asian women. This study also highlights the value of gene-environment interaction analyses in evaluating genetic factors for complex diseases.
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Affiliation(s)
- Ben Zhang
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
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Redox Protein Expression Predicts Radiotherapeutic Response in Early-Stage Invasive Breast Cancer Patients. Int J Radiat Oncol Biol Phys 2011; 79:1532-40. [DOI: 10.1016/j.ijrobp.2010.11.002] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2010] [Revised: 10/29/2010] [Accepted: 11/02/2010] [Indexed: 11/21/2022]
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47
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Peng S, Lü B, Ruan W, Zhu Y, Sheng H, Lai M. Genetic polymorphisms and breast cancer risk: evidence from meta-analyses, pooled analyses, and genome-wide association studies. Breast Cancer Res Treat 2011; 127:309-24. [DOI: 10.1007/s10549-011-1459-5] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2011] [Accepted: 03/15/2011] [Indexed: 12/31/2022]
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Zhang R, Xu G, Chen W, Zhang W. Genetic Polymorphisms of Glutathione S-Transferase P1 and Bladder Cancer Susceptibility in a Chinese Population. Genet Test Mol Biomarkers 2011; 15:85-8. [PMID: 21117956 DOI: 10.1089/gtmb.2010.0162] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Affiliation(s)
- RongGui Zhang
- Department of Urology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - GuangYong Xu
- Department of Urology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - WenJun Chen
- Department of Urology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - WeiLi Zhang
- Department of Urology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
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Cytochrome P450 1A1 Gene Polymorphisms and Endometrial Cancer Risk: A Meta-Analysis. Int J Gynecol Cancer 2011; 21:323-31. [DOI: 10.1097/igc.0b013e31820575c0] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Introduction:This meta-analysis aims to examine whether the genotype status of Msp1, Ile462Val, and Thr461Asn polymorphisms in cytochrome P450 1A1 (CYP1A1) is associated with endometrial cancer risk.Methods:Eligible case-control studies were identified through search in MEDLINE (end of search: August 2010). Pooled odds ratios (ORs) were appropriately derived from fixed-effects or random-effects models.Results:ConcerningMspI polymorphism, 8 studies were eligible (1456 cases and 2371 controls); 9 studies were eligible (1889 cases and 3662 controls) for Ile462Val and 6 studies were eligible (1272 cases and 2122 controls) for Thr461Asn.MspI polymorphism was not associated with endometrial cancer risk (for heterozygous TC vs TT carriers: OR = 0.83, 95% confidence interval [CI], 0.59-1.15, random effects; for homozygous CC vs TT carriers: OR = 1.00, 95% CI, 0.55-1.82, fixed effects). Similarly, Ile462Val polymorphism was not associated with endometrial cancer risk (for heterozygous Ile/Val vs Ile/Ile carriers: OR = 1.27, 95% CI, 0.78-2.06, random effects; for homozygous Val/Val vs Ile/Ile carriers: OR = 1.16, 95% CI, 0.48-2.81, fixed effects). Accordingly, Thr461Asn status was not significantly associated with endometrial cancer risk. The same results were reproduced in Caucasians.Conclusions:The 3 examined CYP1A1 genotype polymorphisms do not seem to confer any additional risk for endometrial cancer in Caucasians. Accumulation of further data seems mandatory for future race-specific analyses.
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Sergentanis TN, Economopoulos KP. Validating the meta-analytical results on MDM2, CASP8, XRCC3 polymorphisms and breast cancer risk: examination of Hardy-Weinberg Equilibrium. Breast Cancer Res Treat 2010; 126:819-23. [PMID: 21161371 DOI: 10.1007/s10549-010-1291-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2010] [Accepted: 11/30/2010] [Indexed: 11/29/2022]
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