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Kim J, Kang SJ, Jo N, Kim SJ, Jang S. Cancer prognosis using base excision repair genes. Mol Cells 2025; 48:100186. [PMID: 39828060 PMCID: PMC11835649 DOI: 10.1016/j.mocell.2025.100186] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 01/10/2025] [Accepted: 01/13/2025] [Indexed: 01/22/2025] Open
Abstract
The base excision repair (BER) pathway is a critical mechanism in genomic stability. This review investigates the role of the BER pathway in advanced cancer therapies considering the pivotal role of genetic factors in cancer patient responses and prognosis. BER factors significantly influence genetic instability and cancer prognosis, as well as the effectiveness of chemotherapy and radiation therapy. In various cancers such as breast, colon, lung, and bladder, BER factors have shown potential as critical biological markers for predicting cancer outcomes. This study focuses on the polymorphisms and expression levels of key BER genes, including OGG1, XRCC1, APE1, and Polβ. Our findings demonstrate that the expression levels of BER genes and proteins are closely associated with the risk, progression, treatment response, and prognosis of various cancers. These insights could improve cancer treatments and aid in the development of drugs targeting BER proteins. Ongoing research in this field requires extensive statistical analyses and large-scale prospective studies to effectively utilize BER protein levels. Ultimately, these results suggest that the BER pathway represents a potential target for cancer diagnosis, prognostic prediction, and the development of personalized therapeutic strategies. This paves the way for effective cancer treatment in the future.
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Affiliation(s)
- Jeongeun Kim
- College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea; Gradutate Program in Innovative Biomaterials Convergence, Ewha Womans University, Seoul 03760, Republic of Korea
| | - Su-Jin Kang
- College of Pharmacy, Dongduk Women's University, Seoul 02748, Republic of Korea
| | - Nayoon Jo
- College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea; Gradutate Program in Innovative Biomaterials Convergence, Ewha Womans University, Seoul 03760, Republic of Korea
| | - Seung-Jin Kim
- Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Republic of Korea.
| | - Sunbok Jang
- College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea; Gradutate Program in Innovative Biomaterials Convergence, Ewha Womans University, Seoul 03760, Republic of Korea.
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Liu J, Zheng J, Guo Y, Sheng X, Yin Y, Qian S, Xu B, Xiong W, Yin X. Association between APE1 rs1760944 and rs1130409 polymorphism with prostate cancer risk: A systematic review and meta-analysis. Medicine (Baltimore) 2021; 100:e27630. [PMID: 34797286 PMCID: PMC8601344 DOI: 10.1097/md.0000000000027630] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Accepted: 10/13/2021] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND Recently, some studies have suggested that the association of apurinic/apyrimidinic endonuclease 1 (APE1) gene polymorphism with prostate cancer (PCa) risk, but there are still some controversies. Hence, we elaborated the relationship between APE1 rs1760944 and rs1130409 gene and PCa risk through systematic literature review and meta-analysis. METHODS As of March 2020, EMBASE, PubMed, the Cochrane Library, Science Direct/Elsevier, MEDLINE and CNKI were used for systematic literature retrieval to investigate the correlation between APE1 rs1760944 and rs1130409 gene polymorphism with PCa risk. Meta-analysis was performed using Review Manager and Stata software. RESULTS Seven studies were distinguished, consists of 1769 cases of PCa patients and 2237 normal controls. Our results illustrated that there are significant correlation between the APE1 rs1760944 gene polymorphism and PCa in all genetic models (P < .05). The combined odds ratios and 95% confidence intervals were as follows: Additive model (ORs 0.62, 95%, CI [0.39, 0.97]); Codominant model (ORs 0.74, 95% CI [0.58, 0.95]); Dominant model (ORs 0.75, 95%, CI [0.59, 0.95]); Recessive model (ORs 0.63, 95% CI [0.41, 0.96]); Allele model (ORs 0.78, 95% CI [0.65, 0.94]). There also have significant associations between APE1 rs1130409 polymorphisms and PCa in all genetic models (P < .05). The combined odds ratios and 95% confidence intervals were as follows: Additive model (ORs 1.37, 95%, CI [1.01, 1.85]); Codominant model (ORs 1.21, 95% CI [1.01, 1.44]); Dominant model (ORs 1.33, 95%, CI [1.02, 1.73]); Recessive model (ORs 1.74, 95% CI [1.06, 2.85]); Allele model (ORs 1.14, 95% CI [1.00, 1.29]). CONCLUSION This study suggests that APE1 rs1760944 polymorphisms might be a protective factor of PCa, and APE1 rs1130409 is suggested to be a risk factor of PCa. APE1 rs1760944 and rs1130409 polymorphisms may be used in the risk assessment of PCa.
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Affiliation(s)
- Jinnian Liu
- Department of Urology, Second People's Hospital of Banan District, Chongqing, China
| | - Jian Zheng
- Department of Urology, Second People's Hospital of Banan District, Chongqing, China
| | - Yu Guo
- Department of Urology, Traditional Chinese Medicine Hospital, Chongqing, China
| | - Xia Sheng
- Department of Urology, Second People's Hospital of Banan District, Chongqing, China
| | - Yongjian Yin
- Department of Urology, Second People's Hospital of Banan District, Chongqing, China
| | - Shengqiang Qian
- Department of Urology, Traditional Chinese Medicine Hospital, Chongqing, China
| | - Bin Xu
- Department of Urology, Traditional Chinese Medicine Hospital, Chongqing, China
| | - Wei Xiong
- Department of Urology, Traditional Chinese Medicine Hospital, Chongqing, China
| | - Xiangrui Yin
- Department of Urology, Traditional Chinese Medicine Hospital, Chongqing, China
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Association between apurinic/apyrimidinic endonuclease 1 rs1760944 T>G polymorphism and susceptibility of cancer: a meta-analysis involving 21764 subjects. Biosci Rep 2020; 39:221420. [PMID: 31804681 PMCID: PMC6923335 DOI: 10.1042/bsr20190866] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2019] [Revised: 10/03/2019] [Accepted: 12/04/2019] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Previous case-control studies have suggested that apurinic/apyrimidinic endonuclease 1 (APE1) rs1760944 T>G polymorphism may be associated with cancer risk. Here, we carried out an updated meta-analysis to focus on the correlation between APE1 rs1760944 T>G locus and the risk of cancer. METHODS We used the crude odds ratios (ORs) with their 95% confidence intervals (CIs) to evaluate the possible relationship between the APE1 rs1760944 T>G polymorphism and cancer risk. Heterogeneity, publication bias and sensitivity analysis were also harnessed to check the potential bias of the present study. RESULTS Twenty-three independent studies involving 10166 cancer cases and 11598 controls were eligible for this pooled analysis. We found that APE1 rs1760944 T>G polymorphism decreased the risk of cancer in four genetic models (G vs. T: OR, 0.87; 95% CI, 0.83-0.92; P<0.001; GG vs. TT: OR, 0.77; 95% CI, 0.69-0.86; P<0.001; GG/TG vs. TT: OR, 0.83; 95% CI, 0.77-0.89, P<0.001 and GG vs. TT/TG: OR, 0.85; 95% CI, 0.80-0.92, P<0.001). Results of subgroup analyses also demonstrated that this single-nucleotide polymorphism (SNP) modified the risk among lung cancer, breast cancer, osteosarcoma, and Asians. Evidence of publication bias was found in the present study. When we treated the publication bias with 'trim-and-fill' method, the adjusted ORs and CIs were not significantly changed. CONCLUSION In conclusion, current evidence highlights that the APE1 rs1760944 T>G polymorphism is a protective factor for cancer susceptibility. In the future, case-control studies with detailed risk factors are needed to confirm or refute our findings.
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A Dual Face of APE1 in the Maintenance of Genetic Stability in Monocytes: An Overview of the Current Status and Future Perspectives. Genes (Basel) 2020; 11:genes11060643. [PMID: 32545201 PMCID: PMC7349382 DOI: 10.3390/genes11060643] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 06/05/2020] [Accepted: 06/08/2020] [Indexed: 12/24/2022] Open
Abstract
Monocytes, which play a crucial role in the immune system, are characterized by an enormous sensitivity to oxidative stress. As they lack four key proteins responsible for DNA damage response (DDR) pathways, they are especially prone to reactive oxygen species (ROS) exposure leading to oxidative DNA lesions and, consequently, ROS-driven apoptosis. Although such a phenomenon is of important biological significance in the regulation of monocyte/macrophage/dendritic cells’ balance, it also a challenge for monocytic mechanisms that have to provide and maintain genetic stability of its own DNA. Interestingly, apurinic/apyrimidinic endonuclease 1 (APE1), which is one of the key proteins in two DDR mechanisms, base excision repair (BER) and non-homologous end joining (NHEJ) pathways, operates in monocytic cells, although both BER and NHEJ are impaired in these cells. Thus, on the one hand, APE1 endonucleolytic activity leads to enhanced levels of both single- and double-strand DNA breaks (SSDs and DSBs, respectively) in monocytic DNA that remain unrepaired because of the impaired BER and NHEJ. On the other hand, there is some experimental evidence suggesting that APE1 is a crucial player in monocytic genome maintenance and stability through different molecular mechanisms, including induction of cytoprotective and antioxidant genes. Here, the dual face of APE1 is discussed.
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Youn HJ, Han W. A Review of the Epidemiology of Breast Cancer in Asia: Focus on Risk Factors. Asian Pac J Cancer Prev 2020; 21:867-880. [PMID: 32334446 PMCID: PMC7445974 DOI: 10.31557/apjcp.2020.21.4.867] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Indexed: 01/11/2023] Open
Abstract
Background and Aim: Breast cancer is the most prevalent cancer in women. To date, regional differences in breast cancer risk factors have not been identified. The aim of our review was to gain a better understanding of the role of risk factors in women with breast cancer in Asia. Methods: We conducted a PubMed search on 15 March 2016, for journal articles published in English between 2011 and 2016, which reported data for human subjects in Asia with a diagnosis of breast cancer. Search terms included breast neoplasm, epidemiology, Asia, prevalence, incidence, risk and cost of illness. Studies of any design were included, except for review articles and meta-analyses, which were excluded to avoid duplication of data. No exclusions were made based on breast cancer treatment. We reported the results using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Results: A total of 776 abstracts were retrieved. After screening against the eligibility criteria, 562 abstracts were excluded. The remaining 214 abstracts, which were published between 2013 and 2015, were included in this review. Results were summarized and reported under three categories: incidence, prevalence or outcomes for breast cancer in Asia; modifiable risk factors; and non-modifiable risk factors. We found that the increased risk of breast cancer among participants from Asia was associated with older age, family history of breast cancer, early menarche, late menopause, high body mass index, being obese or overweight, exposure to tobacco smoke, and high dietary intake of fats or fatty foods. In contrast, intake of dietary fruits, vegetables, and plant- and soy-based products was associated with a decreased breast cancer risk. While based on limited data, when compared to women from the United States, women from Asia had a decreased risk of breast cancer. Conclusions: This review of 214 abstracts of studies in Asia, published between 2013 and 2015, confirmed the relevance of known non-modifiable and modifiable risk factors for women with breast cancer.
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Affiliation(s)
- Hyun Jo Youn
- Department of Surgery, Research Institute of Clinical Medicine, Chonbuk National University and Biomedical Research Institute, Chonbuk National University Hospital, Republic of Korea
| | - Wonshik Han
- Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine, Seoul National University Cancer Hospital, Republic of Korea
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Avazpour N, Hajjari M, Kazemi Nezhad SR, Tahmasebi Birgani M. SNHG1 Long Noncoding RNA is Potentially Up-Regulated in Colorectal Adenocarcinoma. Asian Pac J Cancer Prev 2020; 21:897-901. [PMID: 32334448 DOI: 10.31557/apjcp.2020.21.4.897] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2018] [Indexed: 01/13/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common types of cancer worldwide. However, the molecular mechanisms involved in CRC initiation and progression is remained to be unknown. It seems that lncRNAs, as the main and lengthy functional transcripts of the genome, have important roles in different cancers such as CRC. CRC-related lncRNAs are reported to be involved in diverse molecular processes such as metastasis, invasion, cell proliferation, and apoptosis. This study was aimed to analyse the expression level of lncRNA SNHG1 in colorectal adenocarcinoma and normal tissues. We performed an in silico analysis on a large cohort and confirmed the results by experimental analysis of clinical samples through real-time PCR. Our findings demonstrated that that SNHG1 is potentially overexpressed in tumor tissues compared with adjacent normal tissues. The expression level of SNHG1 was shown to be potentially associated with clinicopathological features of tumors. The current study suggests the potential role of SNHG1 in colon cancer progression.
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Affiliation(s)
- Niloofar Avazpour
- Department of Genetics, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Mohamadreza Hajjari
- Department of Genetics, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | | | - Maryam Tahmasebi Birgani
- Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Liu J, Jia W, Hua RX, Zhu J, Zhang J, Yang T, Li P, Xia H, He J, Cheng J. APEX1 Polymorphisms and Neuroblastoma Risk in Chinese Children: A Three-Center Case-Control Study. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2019; 2019:5736175. [PMID: 31341530 PMCID: PMC6614964 DOI: 10.1155/2019/5736175] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Accepted: 04/30/2019] [Indexed: 02/07/2023]
Abstract
Neuroblastoma is a life-threatening extracranial solid tumor, preferentially occurring in children. However, its etiology remains unclear. APEX1 is a critical gene in the base excision repair (BER) system responsible for maintaining genome stability. Given the potential effects of APEX1 polymorphisms on the ability of the DNA damage repair, many studies have investigated the association between these variants and susceptibility to several types of cancer but not neuroblastoma. Here, we conducted a three-center case-control study to evaluate the association between APEX1 polymorphisms (rs1130409 T>G, rs1760944 T>G, and rs3136817 T>C) and neuroblastoma risk in Chinese children, consisting of 469 cases and 998 controls. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated to evaluate the associations. No significant association with neuroblastoma risk was found for the studied APEX1 polymorphisms in the single locus or combination analysis. Interestingly, stratified analysis showed that rs1130409 GG genotype significantly reduced the risk of tumor in males. Furthermore, we found that carriers with 1-3 protective genotypes had a lower neuroblastoma risk in the children older than18 months and male, when compared to those without protective genotypes. In summary, our data indicate that APEX1 gene polymorphisms may have a weak effect on neuroblastoma susceptibility. These findings should be further validated by well-designed studies with larger sample size.
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Affiliation(s)
- Jiabin Liu
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623 Guangdong, China
| | - Wei Jia
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623 Guangdong, China
| | - Rui-Xi Hua
- Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080 Guangdong, China
| | - Jinhong Zhu
- Department of Clinical Laboratory, Molecular Epidemiology Laboratory, Harbin Medical University Cancer Hospital, Harbin, 150040 Heilongjiang, China
| | - Jiao Zhang
- Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052 Henan, China
| | - Tianyou Yang
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623 Guangdong, China
| | - Peng Li
- Department of Pediatric Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004 Shaanxi, China
| | - Huimin Xia
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623 Guangdong, China
| | - Jing He
- Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, 510623 Guangdong, China
| | - Jiwen Cheng
- Department of Pediatric Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004 Shaanxi, China
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Qiao L, Feng X, Wang G, Zhou B, Yang Y, Li M. Polymorphisms in BER genes and risk of breast cancer: evidences from 69 studies with 33760 cases and 33252 controls. Oncotarget 2018; 9:16220-16233. [PMID: 29662639 PMCID: PMC5882330 DOI: 10.18632/oncotarget.23804] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Accepted: 11/27/2017] [Indexed: 02/06/2023] Open
Abstract
Recently, numerous studies have reported an association between single nucleotide polymorphisms in base-excision repair genes and the risk of developing breast cancer, however there is no consensus. The aim of this meta-analysis was to review and quantitatively assess the relationship between single nucleotide polymorphisms in base-excision repair genes and breast cancer risk. The results suggested that a mutation of T to G in rs1760944 may lead to a higher risk of developing breast cancer in the Mongoloid population, and G to A of rs25487 significantly reduced the risk of breast cancer in Mongoloid and Caucasoid populations. In contrast to the CC and CG genotypes, the GG genotype of rs1052133 located on theOGG1 gene appeared to be a protective factor against developing breast cancer in both Mongoloid and Caucasoid populations. There was no evidence to suggest that rs25489, rs1799782, rs1130409, rs1805414 and rs1136410 were associated with breast cancer risk. In conclusion, this study provides evidence to support the theory that DNA repair genes are associated with breast cancer risk, providing information to further understand breast cancer etiology. and The potential biological pathways linking DNA repair, ethnic background, environment and breast cancer require further investigation.
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Affiliation(s)
- Lele Qiao
- The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China
| | - Xiaoshan Feng
- The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China
| | - Gongping Wang
- The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China
| | - Bo Zhou
- The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China
| | - Yantong Yang
- The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China
| | - Mengxiang Li
- Henan University of Science and Technology, LuoYang, Henan, 471023, China
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Meng Q, Wang S, Tang W, Wu S, Gao N, Zhang C, Cao X, Li X, Zhang Z, Aschner M, Jin H, Huang Y, Chen R. XRCC1 mediated the development of cervival cancer through a novel Sp1/Krox-20 swich. Oncotarget 2017; 8:86217-86226. [PMID: 29156789 PMCID: PMC5689679 DOI: 10.18632/oncotarget.21040] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2017] [Accepted: 08/09/2017] [Indexed: 01/18/2023] Open
Abstract
Cervical cancer is the second leading cause of mortality among women. Impairment of the base excision repair (BER) pathway is one of the major causes of the initiation and progression of cervical cancer. However, whether the polymorphisms of the BER pathway components (i.e., HOGG1, XRCC1, ADPRT, and APE1) can affect the risk of cervical cancer remains unknown. Herein, we applied a hospital-based case-control study covering two independent cohorts and a subsequent functional assay to determine the roles of the single nucleotide polymorphisms (SNPs) of the BER pathway genes in cervical cancer. Results indicated that the XRCC1 rs3213245 (-77TC) TT genotype was associated with an increased risk of cervical cancer. The immunohistochemistry assay showed that XRCC1 protein expression levels were upregulated in cervical cancer patients with the XRCC1 rs3213245 CC genotype compared with the CT or TT genotypes. Further, results from ChIP assay showed that Sp1 could bind to the −77 site and that the rs3213245 C genotype promoted the binding of Sp1 to the XRCC1 promoter. Moreover, ChIP/Re-ChIP assays revealed that transcription factor Krox-20 was recruited to the XRCC1 rs3213245 mutation region and regulated the transcription of the XRCC1 gene by interacting with Sp1, ultimately mediated cervical cancer development. In summary, the findings indicated that the functional XRCC1 SNP rs3213245 was associated with the risk of cervical cancer based on the Sp1/Krox-20 switch.
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Affiliation(s)
- Qingtao Meng
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China
| | - Shizhi Wang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China
| | - Weiyan Tang
- Medical Oncology, Jiangsu Cancer Hospital, Nanjing, China
| | - Shenshen Wu
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China
| | - Na Gao
- Institute of Bioinformatics, Heinrich Heine University, Düsseldorf, Germany
| | - Chengcheng Zhang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China
| | - Xiaoli Cao
- Clinical Lab, Nantong Tumor Hospital, Nantong, China
| | - Xiaobo Li
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China
| | - Zhengdong Zhang
- Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing, China
| | - Michael Aschner
- Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Hua Jin
- Core Laboratory, Nantong Tumor Hospital, Nantong, China
| | - Yue Huang
- Department of Pathology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Rui Chen
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.,State Key Laboratory of Respiratory Disease, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou, China
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Krupa R, Czarny P, Wigner P, Wozny J, Jablkowski M, Kordek R, Szemraj J, Sliwinski T. The Relationship Between Single-Nucleotide Polymorphisms, the Expression of DNA Damage Response Genes, and Hepatocellular Carcinoma in a Polish Population. DNA Cell Biol 2017; 36:693-708. [PMID: 28598207 DOI: 10.1089/dna.2017.3664] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
The molecular mechanism of hepatocellular carcinoma (HCC) is related to DNA damage caused by oxidative stress products induced by hepatitis B virus (HBV) or C (HCV) infection and exposure to environmental pollutants. Single-nucleotide polymorphisms (SNPs) of DNA damage response (DDR) genes may influence individual susceptibility to environmental risk factors and affect DNA repair efficacy, which, in turn, can influence the risk of HCC. The study evaluates a panel of 15 SNPs in 11 DDR genes (XRCC1, XRCC3, XPD, MUTYH, LIG1, LIG3, hOGG1, PARP1, NFIL1, FEN1, and APEX1) in 65 HCC patients, 50 HBV- and 50 HCV-infected non-cancerous patients, and 50 healthy controls. It also estimates the mRNA expression of nine DDR genes in cancerous and adjacent healthy liver tissues. Two of the investigated polymorphisms (rs1052133 and rs13181) were associated with HCC risk. For all investigated genes, the level of mRNA was significantly lower in HCC cancer tissue than in non-cancerous liver tissue. Seven of the investigated polymorphisms were statistically related to gene expression in cancer tissues. The disruption of DDR genes may be responsible for hepatocellular transformation in HCV-infected patients.
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Affiliation(s)
- Renata Krupa
- 1 Department of Molecular Genetics, University of Lodz , Lodz, Poland
| | - Piotr Czarny
- 2 Department of Medical Biochemistry, Medical University of Lodz , Lodz, Poland
| | - Paulina Wigner
- 1 Department of Molecular Genetics, University of Lodz , Lodz, Poland
| | - Joanna Wozny
- 3 Department of Infectious and Liver Diseases, Medical University of Lodz , Lodz, Poland
| | - Maciej Jablkowski
- 3 Department of Infectious and Liver Diseases, Medical University of Lodz , Lodz, Poland
| | - Radzislaw Kordek
- 4 Department of Pathology, Medical University of Lodz , Lodz, Poland
| | - Janusz Szemraj
- 2 Department of Medical Biochemistry, Medical University of Lodz , Lodz, Poland
| | - Tomasz Sliwinski
- 1 Department of Molecular Genetics, University of Lodz , Lodz, Poland
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Lu Z, Li S, Ning S, Yao M, Zhou X, Wu Y, Zhong C, Yan K, Wei Z, Xie Y. Association of the rs1760944 polymorphism in the APEX1 base excision repair gene with risk of nasopharyngeal carcinoma in a population from an endemic area in South China. J Clin Lab Anal 2017; 32. [PMID: 28464393 DOI: 10.1002/jcla.22238] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2017] [Accepted: 03/23/2017] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Apurinic/apyrimidinic endonuclease 1 (APEX1) plays a central role in the repair of oxidative DNA lesions via base excision repair, and polymorphism in the APEX1 gene may affect susceptibility to carcinogenesis. METHODS Here, we assessed possible relationships between single-nucleotide polymorphism at APEX1 rs1760944 and risk of nasopharyngeal carcinoma (NPC) in 477 NPC patients and 558 healthy controls from Guangxi province, which is the second largest NPC endemic area in South China. RESULTS Genotype frequencies in controls were in Hardy-Weinberg equilibrium. Logistic regression analysis identified the genotypes GT or GG as associated with significantly lower risk than the genotype TT (adjusted odds ratio [OR] 0.745, 95% confidence interval [CI] 0.573-0.970). This apparent protective effect of GT/GG was even greater among those with no smoking history (adjusted OR 0.679, 95%CI 0.494-0.934). CONCLUSION Our results suggest that APEX1 rs1760944 polymorphism may correlate with NPC susceptibility in a population from an endemic area in South China.
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Affiliation(s)
- Zhifang Lu
- Graduate School of Guangxi Medical University, Nanning, China
| | - Sisi Li
- Graduate School of Guangxi Medical University, Nanning, China
| | - Sisi Ning
- Graduate School of Guangxi Medical University, Nanning, China
| | - Mengwei Yao
- Graduate School of Guangxi Medical University, Nanning, China
| | - Xunzhao Zhou
- Graduate School of Guangxi Medical University, Nanning, China
| | - Yuan Wu
- Graduate School of Guangxi Medical University, Nanning, China
| | - Changtao Zhong
- Graduate School of Guangxi Medical University, Nanning, China
| | - Kui Yan
- Graduate School of Guangxi Medical University, Nanning, China
| | - Zhengbo Wei
- Department of Head and Neck Tumor Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
| | - Ying Xie
- Guangxi Key Laboratory for High-Incidence Tumor Prevention and Treatment, Experimental Center of Medical Science of Guangxi Medical University, Nanning, China
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Ren HT, Li YM, Wang XJ, Kang HF, Jin TB, Ma XB, Liu XH, Wang M, Liu K, Xu P, Yao QL, Dai ZJ. PD-1 rs2227982 Polymorphism Is Associated With the Decreased Risk of Breast Cancer in Northwest Chinese Women: A Hospital-Based Observational Study. Medicine (Baltimore) 2016; 95:e3760. [PMID: 27227944 PMCID: PMC4902368 DOI: 10.1097/md.0000000000003760] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2015] [Revised: 04/24/2016] [Accepted: 05/02/2016] [Indexed: 02/06/2023] Open
Abstract
Programmed death-1 (PD-1) is crucial in cancer and is well characterized as a negative T-cell regulator that functions by delivering inhibitory signals. We aimed to evaluate the relationship between PD-1 polymorphisms (rs10204525, rs2227982, and rs7421861) and breast cancer risk.We selected 560 breast cancer patients and 583 age-, sex-, and ethnicity-matched healthy controls from Northwest China. The PD-1 polymorphisms were genotyped by using Sequenom MassARRAY. Associations were estimated with odds ratios (ORs) and 95% confidence intervals (95% CIs).For the rs10204525 and rs7421861 polymorphisms, no differences in breast cancer risk were found in any of the genetic models. For the rs2227982 polymorphism, the variant genotypes were significantly associated with decreased breast cancer risk (CT vs CC: OR = 0.68, 95% CI = 0.52-0.91; CT + TT vs CC: OR = 0.69, 95% CI = 0.53-0.90). In analyses stratified by age, the decreased risk was observed among the younger subjects (OR = 0.68, 95% CI = 0.47-0.97). We found that the decreased risk observed for the variant genotypes of rs2227982 was associated with the Her-2 status (CT vs CC: OR = 0.55, 95% CI = 0.37-0.84; CT + TT vs CC: OR = 0.56, 95% CI = 0.38-0.82). The haplotype analysis showed that the Ars10204525 Trs2227982 Crs7421861 haplotype was associated with a significantly decreased risk of breast cancer (OR = 0.50, 95% CI = 0.34-0.75).Our findings support an association between the PD-1 rs2227982 polymorphism and decreased breast cancer risk, especially in Her-2 positive breast cancer patients in the Chinese population.
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Affiliation(s)
- Hong-Tao Ren
- From the Departments of Oncology (H-TR, X-JW, H-FK, X-BM, X-HL, MW, KL, PX, Q-LY, Z-JD) and General Surgery (Y-ML), The Second Affiliated Hospital of Xi'an Jiaotong University; and National Engineering Research Center for Miniaturized Detection Systems, School of Life Sciences, Northwest University, Xi'an, China (T-BJ)
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Yousefi M, Salehi Z, Mashayekhi F, Bahadori MH. The association of ApE1 -656T>G and 1349T>G polymorphisms and idiopathic male infertility risk. Int Urol Nephrol 2015; 47:921-6. [PMID: 25917483 DOI: 10.1007/s11255-015-0979-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Accepted: 04/09/2015] [Indexed: 11/30/2022]
Abstract
PURPOSE In spite of variety studies in understanding of human reproductive and fertility, the underlying causes of male infertility remains undefined in about 50 % of cases. The polymorphism studies have a crucial role in diseases recognizing. Human apurinic/apyrimidinic endonuclease 1 (ApE1) is a multifunctional protein that has an important role in the base excision repair pathway. The present study was aimed to evaluate whether two polymorphisms -656T>G and 1349T>G ApE1 are related with the susceptibility to idiopathic male infertility. METHODS Samples were collected from 180 patients diagnosed with idiopathic male infertility and 120 control subjects and genotyped by tetra-primer amplification refractory mutation system PCR. RESULTS We observed a significant difference in genotype distributions of -656T>G ApE1 polymorphism between infertile patients and controls (P = 0.0001). Our findings indicated individuals with the variant TG genotypes had a significant increased risk of idiopathic male infertility (OR 1.84, 95 % CI 1.09-3.11, P = 0.021), whereas the significant association between the 1349T>G polymorphism and idiopathic male infertility risk was not observed (P = 0.2). CONCLUSIONS Our data suggest that the -656T>G ApE1 polymorphism may be associated with increased risk of idiopathic male infertility. Larger studies with more patients and controls are needed to confirm the results.
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Affiliation(s)
- Mostafa Yousefi
- Department of Biology, Faculty of Sciences, University of Guilan, P.O. Box 1914, Rasht, Iran
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Dai ZJ, Shao YP, Kang HF, Tang W, Xu D, Zhao Y, Liu D, Wang M, Yang PT, Wang XJ. Relationship between apurinic endonuclease 1 Asp148Glu polymorphism and gastrointestinal cancer risk: An updated meta-analysis. World J Gastroenterol 2015; 21:5081-5089. [PMID: 25945024 PMCID: PMC4408483 DOI: 10.3748/wjg.v21.i16.5081] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2014] [Revised: 10/28/2014] [Accepted: 12/05/2014] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the relationship between apurinic endonuclease 1 (APE1) Asp148Glu polymorphism and the susceptibility to gastrointestinal (GI) cancers. METHODS We searched PubMed, ISI Web of Knowledge, and Chinese National Knowledge Infrastructure (CNKI) databases updated on July 15, 2014 for relevant studies. Only case-control studies comparing APE1 Asp148Glu polymorphism and GI cancer risk were included. We excluded studies reporting only standardized incidence ratios without control groups and those without detailed genotyping data. Meta-analysis was performed on 17 studies involving 4856 cancer patients and 6136 cancer-free controls. Review Manager version 5.1 was used to perform the meta-analysis. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated under the allele contrast, homozygous, heterozygous, dominant and recessive genetic models. We also conducted subgroup analyses stratified by ethnicity and cancer type. Publication bias was evaluated using Begg's test. RESULTS The meta-analysis showed a significant association between APE1 Asp148Glu polymorphism and GI cancer risk in three genetic models in the overall population (G vs T: OR = 1.18; 95%CI: 1.05-1.32; TG vs TT: OR = 1.28; 95%CI: 1.08-1.52; TG + GG vs TT: OR = 1.32; 95%CI: 1.10-1.57). Stratified analysis by ethnicity revealed a statistically increased GI cancer risk in Asians (G vs T: OR = 1.27; 95%CI: 1.07-1.51; GG vs TT: OR = 1.58; 95%CI: 1.05-2.38; TG vs TT: OR = 1.30; 95%CI, 1.01- 1.67; and TG + GG vs TT: OR = 1.38; 95%CI: 1.07-1.78), but not in Caucasians. Further subgroup analysis by cancer type indicated that APE1 Asp148Glu polymorphism may contribute to gastric cancer risk. However, Asp148Glu has no significant association with colorectal or esophageal cancer risk in any genetic model. CONCLUSION This meta-analysis suggests that the APE1 Asp148Glu polymorphism G allele is associated with an increased GI cancer risk, especially in gastric cancer.
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Ma X, Kang H, Dai Z, Ma L, Jin Y, Wang X. Impact of the IGFBP3 A-202C polymorphism on susceptibility and clinicopathologic features of breast cancer. Biomed Pharmacother 2015; 71:108-111. [PMID: 25960224 DOI: 10.1016/j.biopha.2015.02.018] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2015] [Accepted: 02/15/2015] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Insulin-like growth factor binding protein 3 (IGFBP3) plays an important role in cellular proliferation, differentiation, apoptosis, and mammary carcinogenesis. Genetic variations in IGFBP3 have been identified to influence the circulating IGFBP3 level. The present study determined the impact of an important promoter polymorphism (A-202C, rs2854744) on susceptibility and progression of breast cancer in a Chinese population. METHODS We genotyped the IGFBP3 A-202C polymorphism in a case-control study involving 465 breast cancer patients and 799 age-matched, cancer-free controls using the TaqMan method. Logistic regression was used to assess the genetic association between the occurrence and progression of breast cancer. RESULTS Compared with the wild genotype (-202AA), we found a statistically significant increased risk of breast cancer associated with the variant genotypes (CC vs. AA: OR=2.00, 95% CI=1.25-3.21; AC+CC vs. AA: OR=1.34, 95% CI=1.06-1.70). In the stratified analysis, the increased risk was more apparent among the subgroups of older subjects (OR=1.70, 95% CI=1.20-2.42). Furthermore, we found that patients carrying variant genotypes (AC+CC) had a significantly greater prevalence of large tumor size (OR=1.72, 95% CI=1.13-2.64; P=0.021). CONCLUSION Our results suggest that the functional IGFBP3 A-202C polymorphism may influence the susceptibility and progression of breast cancer in the Chinese population.
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Affiliation(s)
- Xiaobin Ma
- Department of Oncology, the Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, China
| | - Huafeng Kang
- Department of Oncology, the Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, China.
| | - Zhijun Dai
- Department of Oncology, the Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, China
| | - Li Ma
- Department of Oncology, the Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, China
| | - Yaofeng Jin
- Department of Oncology, the Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, China
| | - Xijing Wang
- Department of Oncology, the Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, China
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Patrono C, Sterpone S, Testa A, Cozzi R. Polymorphisms in base excision repair genes: Breast cancer risk and individual radiosensitivity. World J Clin Oncol 2014; 5:874-882. [PMID: 25493225 PMCID: PMC4259949 DOI: 10.5306/wjco.v5.i5.874] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2013] [Revised: 04/03/2014] [Accepted: 04/17/2014] [Indexed: 02/06/2023] Open
Abstract
Breast cancer (BC) is the most common cancer among women worldwide. The aetiology and carcinogenesis of BC are not clearly defined, although genetic, hormonal, lifestyle and environmental risk factors have been established. The most common treatment for BC includes breast-conserving surgery followed by a standard radiotherapy (RT) regimen. However, radiation hypersensitivity and the occurrence of RT-induced toxicity in normal tissue may affect patients’ treatment. The role of DNA repair in cancer has been extensively investigated, and an impaired DNA damage response may increase the risk of BC and individual radiosensitivity. Single nucleotide polymorphisms (SNPs) in DNA repair genes may alter protein function and modulate DNA repair efficiency, influencing the development of various cancers, including BC. SNPs in DNA repair genes have also been studied as potential predictive factors for the risk of RT-induced side effects. Here, we review the literature on the association between SNPs in base excision repair (BER) genes and BC risk. We focused on X-ray repair cross complementing group 1 (XRCC1), which plays a key role in BER, and on 8-oxoguanine DNA glycosylase 1, apurinic/apyrimidinic endonuclease 1 and poly (ADP-ribose) polymerase-1, which encode three important BER enzymes that interact with XRCC1. Although no association between SNPs and radiation toxicity has been validated thus far, we also report published studies on XRCC1 SNPs and variants in other BER genes and RT-induced side effects in BC patients, emphasising that large well-designed studies are needed to determine the genetic components of individual radiosensitivity.
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Human AP endonuclease 1: a potential marker for the prediction of environmental carcinogenesis risk. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2014; 2014:730301. [PMID: 25243052 PMCID: PMC4158471 DOI: 10.1155/2014/730301] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/25/2014] [Accepted: 06/30/2014] [Indexed: 12/15/2022]
Abstract
Human apurinic/apyrimidinic endonuclease 1 (APE1) functions mainly in DNA repair as an enzyme removing AP sites and in redox signaling as a coactivator of various transcription factors. Based on these multifunctions of APE1 within cells, numerous studies have reported that the alteration of APE1 could be a crucial factor in development of human diseases such as cancer and neurodegeneration. In fact, the study on the combination of an individual's genetic make-up with environmental factors (gene-environment interaction) is of great importance to understand the development of diseases, especially lethal diseases including cancer. Recent reports have suggested that the human carcinogenic risk following exposure to environmental toxicants is affected by APE1 alterations in terms of gene-environment interactions. In this review, we initially outline the critical APE1 functions in the various intracellular mechanisms including DNA repair and redox regulation and its roles in human diseases. Several findings demonstrate that the change in expression and activity as well as genetic variability of APE1 caused by environmental chemical (e.g., heavy metals and cigarette smoke) and physical carcinogens (ultraviolet and ionizing radiation) is likely associated with various cancers. These enable us to ultimately suggest APE1 as a vital marker for the prediction of environmental carcinogenesis risk.
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Gao J, Kang HF, Ma XB, Tang W, Liu D, Zhao Y, Zhang SQ, Guan HT, Lin S, Ren HT, Wang XJ, Dai ZJ. Functional promoter -765 G > C variant in COX-2 gene is associated with the susceptibility of breast cancer in Chinese Han women. Cancer Cell Int 2014; 14:38. [PMID: 24826080 PMCID: PMC4018614 DOI: 10.1186/1475-2867-14-38] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2013] [Accepted: 04/30/2014] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND Cyclooxygenase (COX) is a rate-limiting enzyme in prostaglandins synthesis which exists in two isoforms, COX-1 and COX-2. Over-expression of COX-2 was considered to increase the proliferation and enhance the invasiveness of breast cancer cells. It was suggested that genetic variations in COX-2 could influence its expression. Herein, the present study was aimed to investigate the associations between two mostly studied functional polymorphisms (-765 G > C and 8473 C > T) in COX-2 and breast cancer risk in Chinese Han women. METHODS In the hospital-based case-control study, 465 breast cancer patients and 799 cancer-free controls were genotyped for the COX-2 -765 G > C and 8473 C > T polymorphisms using TaqMan assay. We estimated odds ratios (ORs) and 95% confidence intervals (95% CIs) using the logistic regression. RESULTS Compared with the wild genotype of -765 G > C, we found a statistically significant increased risk of breast cancer associated with the variant genotypes [GC/CC vs. GG: OR = 1.56, 95% CI = 1.11-2.21]. In the stratified analysis, the increased risk was more predominant among the subgroups of younger subjects (OR = 1.61, 95% CI = 1.00-2.61). Furthermore, the variant genotypes were associated with large tumor size (OR = 3.01, 95% CI = 1.47-6.12). No significant association was observed for the 8473 C > T polymorphism. CONCLUSIONS Our results suggest that the functional -765 G > C polymorphism in the promoter of COX-2 may influence the susceptibility and progression of breast cancer in the Chinese Han population.
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Affiliation(s)
- Jie Gao
- Department of Oncology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
- Department of Nephrology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Hua-Feng Kang
- Department of Oncology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Xiao-Bin Ma
- Department of Oncology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Wei Tang
- School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi’an 710061, Shaanxi Province, China
| | - Di Liu
- Department of Oncology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Yang Zhao
- Department of Oncology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Shu-Qun Zhang
- Department of Oncology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Hai-Tao Guan
- Department of Oncology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Shuai Lin
- Department of Oncology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Hong-Tao Ren
- Department of Oncology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Xi-Jing Wang
- Department of Oncology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
| | - Zhi-Jun Dai
- Department of Oncology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710004, China
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Dai ZJ, Wang XJ, Kang AJ, Ma XB, Min WL, Lin S, Zhao Y, Yang PT, Wang M, Kang HF. Association between APE1 Single Nucleotide Polymorphism (rs1760944) and Cancer Risk: a Meta-Analysis Based on 6,419 Cancer Cases and 6,781 Case-free Controls. J Cancer 2014; 5:253-259. [PMID: 24665350 PMCID: PMC3963083 DOI: 10.7150/jca.8085] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2013] [Accepted: 02/01/2014] [Indexed: 02/06/2023] Open
Abstract
Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential enzyme in the base excision repair pathway. Epidemiological studies have suggested associations between APE1 rs1760944 polymorphism and cancer risk. This study was aimed to evaluate the relationship between APE1 rs1760944 polymorphism and cancer risk. We searched Pubmed, ISI Web of Knowledge, Embase, Chinese National Knowledge Infrastructure (CNKI) databases until September 2013 to identify eligible studies. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to estimate the strength of the associations. 12 studies from 11 articles on APE1 rs1760944 genotypes and cancer risk were identified, including a total of 6,419 cancer cases and 6,781 case-free controls. Overall, APE1 rs1760944 polymorphism was significantly associated with the decreased risk of cancer in any genetic models (G vs. T: OR = 0.86, 95% CI = 0.82-0.90; homozygote comparison: OR = 0.74, 95% CI = 0.67-0.82; heterozygote comparison: OR =0.88, 95%CI = 0.81-0.95; dominant model TG+GG vs. TT: OR = 0.82, 95% CI = 0.76-0.89; recessive model GG vs. TT+TG: OR = 0.81, 95%CI = 0.75-0.88). In the stratified analysis by populations, the effect was remain in studies of Asian population (homozygote comparison: OR = 0.71, 95%CI = 0.63-0.79; heterozygote comparison: OR = 0.86, 95 %CI = 0.79- 0.94; dominant model: OR = 0.80, 95% CI = 0.74 -0.87 and recessive model: OR = 0.78, 95%CI = 0.71-0.86). Moreover, a significantly decreased risk was found in lung cancer studies (homozygote comparison: OR = 0.68, 95% CI = 0.59-0.79; heterozygote comparison: OR = 0.86, 95%CI = 0.77- 0.98; dominant model: OR = 0.80, 95%CI = 0.72-0.90 and recessive model: OR= 0.77, 95% CI= 0.68-0.87). These findings support that APE1 rs1760944 polymorphism has a possible protective effect on cancer susceptibility particularly among Asians. Further studies based on different ethnicity and various cancer types are warranted to verify our findings.
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Affiliation(s)
- Zhi-Jun Dai
- 1. Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Xi-Jing Wang
- 1. Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - An-Jing Kang
- 2. Department of Pathology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Xiao-Bin Ma
- 1. Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Wei-Li Min
- 1. Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Shuai Lin
- 1. Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Yang Zhao
- 1. Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Peng-Tao Yang
- 1. Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Meng Wang
- 1. Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
| | - Hua-Feng Kang
- 1. Department of Oncology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China
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The association between the APE1 Asp148Glu polymorphism and breast cancer susceptibility: a meta-analysis based on case–control studies. Tumour Biol 2014; 35:4727-34. [DOI: 10.1007/s13277-014-1618-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2013] [Accepted: 01/03/2014] [Indexed: 01/11/2023] Open
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Association study of germline variants in CCNB1 and CDK1 with breast cancer susceptibility, progression, and survival among Chinese Han women. PLoS One 2013; 8:e84489. [PMID: 24386390 PMCID: PMC3873991 DOI: 10.1371/journal.pone.0084489] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2013] [Accepted: 11/15/2013] [Indexed: 11/19/2022] Open
Abstract
The CCNB1 and CDK1 genes encode the proteins of CyclinB1 and CDK1 respectively, which interact with each other and are involved in cell cycle regulation, centrosome duplication and chromosome segregation. This study aimed to investigate whether the genetic variants in these two genes may affect breast cancer (BC) susceptibility, progression, and survival in Chinese Han population using haplotype-based analysis. A total of ten tSNPs spanning from 2kb upstream to 2kb downstream of these genes were genotyped in 1204 cases and 1204 age-matched cancer-free controls. The haplotype blocks were determined according to our genotyping data and linkage disequilibrium (LD) status of these SNPs. For CCNB1, rs2069429 was significantly associated with increased BC susceptibility under recessive model (OR=2.352, 95%CI=1.480-3.737), so was the diplotype TAGT/TAGT (OR=1.947 95%CI=1.154-3.284, P=0.013). In addition, rs164390 was associated with Her2-negative BC. For CDK1, rs2448343 and rs1871446 were significantly associated with decreased BC risk under dominant models, so was the haplotype ATATT. These two SNPs also showed a dose-dependent effect on BC susceptibility. Using stratified association analysis, we found that women with the heterozygotes or minor allele homozygotes of rs2448343 had much less BC susceptibility among women with BMI<23. In CDK1, three closely located SNPs, rs2448343, rs3213048 and rs3213067, were significantly associated with tumor’s PR status: the heterozygotes of rs2448343 were associated with PR-positive tumors, while the minor allele homozygotes of rs3213048 and heterozygotes of rs3213067 were associated with PR-negative BC tumors. In survival analysis, rs1871446 was associated with unfavorable event-free survival under recessive model, so was the CDK1 diplotype ATATG/ATATG, which carried the minor allele homozygote of rs1871446. Our study indicates that genetic polymorphisms of CCNB1 and CDK1 are related to BC susceptibility, progression, and survival in Chinese Han women. Further studies need to be performed in other populations as an independent replication to verify these results.
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