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nucleotide excision repair gene polymorphisms and hepatoblastoma susceptibility in Eastern Chinese children:A five-center case-control study

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Chinese Journal of Cancer Research 2024年第3期36卷 298-305页

作者： Huimin Yin Xianqiang Wang Shouhua Zhang Shaohua He Wenli Zhang Hongting Lu Yizhen Wang Jing He Chunlei Zhou Department of Pediatric Surgery Guangzhou Institute of PediatricsGuangdong Provincial Key Laboratory of Research in Structural Birth Defect DiseaseGuangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhou 510623China Department of Pediatric Surgery Senior Department of Pediatricsthe Seventh Center of Chinese People’s Liberation Army(PLA)General HospitalBeijing 100000China Department of General Surgery Jiangxi Provincial Children’s HospitalNanchang 330006China Department of Pediatric Surgery Shengli Clinical Medical College of Fujian Medical UniversityFuzhou 350001China Department of Pediatric Surgery Qingdao Women and Children’s HospitalQingdao 266000China Department of Pathology Anhui Provincial Children’s HospitalHefei 230051China Department of Pathology Children’s Hospital of Nanjing Medical UniversityNanjing 210008China

Objective:nucleotide excision repair(NER)plays a vital role in maintaining genome stability,and the effect of NER gene polymorphisms on hepatoblastoma susceptibility is still under *** study aimed to evaluate the relationship between NER gene polymorphisms and the risk of hepatoblastoma in Eastern Chinese Han ***:In this five-center case-control study,we enrolled 966 subjects from East China(193 hepatoblastoma patients and 773 healthy controls).The TaqMan method was used to genotype 19 single nucleotide polymorphisms(SNPs)in NER pathway genes,including ERCC1,XPA,XPC,XPD,XPF,and ***,multivariate logistic regression analysis was performed,and odds ratios(ORs)and 95%confidence intervals(95%CIs)were utilized to assess the strength of ***:Three SNPs were related to hepatoblastoma *** rs2229090 and XPD rs3810366 significantly contributed to hepatoblastoma risk according to the dominant model(adjusted OR=1.49,95%CI=1.07−2.08,P=0.019;adjusted OR=1.66,95%CI=1.12−2.45,P=0.012,respectively).However,XPD rs238406 conferred a significantly decreased risk of hepatoblastoma under the dominant model(adjusted OR=0.68,95%CI=0.49−0.95;P=0.024).Stratified analysis demonstrated that these significant associations were more prominent in certain ***,there was evidence of functional implications of these significant SNPs suggested by online expression quantitative trait loci(eQTLs)and splicing quantitative trait loci(sQTLs)***:In summary,NER pathway gene polymorphisms(XPC rs2229090,XPD rs3810366,and XPD rs238406)are significantly associated with hepatoblastoma risk,and further research is required to verify these findings.

关键词： nucleotide excision repair polymorphisms hepatoblastoma susceptibility

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nucleotide excision repair pathway gene polymorphisms are associated with risk and prognosis of colorectal cancer

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World Journal of Gastroenterology 2020年第3期26卷 307-323页

作者： Yan-Ke Li Qian Xu Li-Ping Sun Yue-Hua Gong Jing-Jing Jing Cheng-Zhong Xing Yuan Yuan Tumor Etiology and Screening Department of Cancer Institute and General Surgery Key Laboratory of Cancer Etiology and Prevention of Liaoning Education DepartmentKey Laboratory of GI Cancer Etiology and Prevention of Liaoning Provincethe First Hospital of China Medical UniversityShenyang 110001Liaoning ProvinceChina Department of Anorectal Surgery the First Hospital of China Medical UniversityShenyang 110001Liaoning ProvinceChina

BACKGROUND Single nucleotide polymorphisms(SNPs)are universally present in nucleotide excision repair(NER)pathway genes,which could make impacts on colorectal carcinogenesis and *** To explore the association of all tagSNPs in NER pathway genes with colorectal cancer(CRC)risk and prognosis in a northern Chinese population by a two-stage case-control design composed of a discovery and validation *** Genotyping for NER SNPs was performed using kompetitive allele specific *** the discovery stage,39 tagSNPs in eight genes were genotyped in 368 subjects,including 184 CRC cases and 184 individual-matched *** the validation stage,13 SNPs in six genes were analyzed in a total of 1712 subjects,including 854 CRC cases and 858 CRC-free *** Two SNPs(XPA rs10817938 and XPC rs2607775)were associated with an increased CRC risk in overall and stratification *** cumulative and interaction effects were also demonstrated in the studied SNPs on CRC *** two SNPs(ERCC2 rs1052555 and ERCC5 rs2228959)were newly found to be associated with a poor overall survival of CRC *** Our findings suggest novel SNPs in NER pathway genes that can be predictive for CRC risk and prognosis in a large-scale Chinese *** present study has referential values for the identification of all-round NER-based genetic biomarkers in predicting the susceptibility and clinical outcome of CRC.

关键词： nucleotide excision repair Polymorphism Colorectal cancer Susceptibility Prognosis

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Diffusion of nucleotide excision repair protein XPA along DNA by coarse-grained molecular simulations

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Chinese Physics B 2021年第10期30卷 680-688页

作者： Weiwei Zhang Jian Zhang National Laboratory of Solid State Microstructures School of PhysicsCollaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210093China

Protein XPA plays critical roles in nucleotide excision repair *** experimental work showed that the functional dynamics of XPA involves the one-dimensional diffusion along DNA to search the damage ***,we investigate the involved dynamical process using extensive coarse-grained molecular simulations at various salt *** results demonstrated strong salt concentration dependence of the diffusion *** low salt concentrations,the one-dimensional diffusion with rotational coupling is the dominant *** high salt concentrations,the diffusion by three-dimensional mechanism becomes more *** wide range of salt concentrations,the residues involved in the DNA binding are similar and the one-dimensional diffusion of XPA along DNA displays sub-diffusive *** sub-diffusive feature is tentatively attributed to diverse strengths of XPA-DNA *** addition,we showed that both binding to DNA and increasing salt concentration tend to stretch the conformation of the XPA,which increases the exposure extent of the sites for the binding of other repair proteins.

关键词： nucleotide excision repair XPA one-dimensional diffusion along DNA molecular simulation

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DNA repair Gene Polymorphisms in the nucleotide excision repair Pathway and Lung Cancer Risk: A Meta-analysis

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Chinese Journal of Cancer Research 2011年第2期23卷 79-91页

作者： Chao-rong Mei Meng Luo Hong-mei Li Wen-jun Deng Qing-hua Zhou Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment Tianjin Lung Cancer Institute Tianjin Medical University General Hospital Tianjin 300052 China West China Hospital Sichuan University Chengdu 610041 China Cancer Center the Affiliated Hospital Qingdao University Medical College Qingdao 266003 China

Objective： A number of studies have reported the association of ＂XPA＂, ＂XPC＂, ＂XPD/ERCC2＂ gene polymorphisms with lung cancer risk. However, the results were conflict. To clarify the impact of polymorphisms of ＂XPA＂, ＂XPC＂, ＂XPD/ERCC2＂, on lung cancer risk, a meta-analysis was performed in this study. Methods： The electronic databases PubMed and Embase were retrieved for studies included in this meta-analysis by ＂XPA＂, ＂XPC＂, ＂XPD/ERCC2＂, ＂lung＂, ＂cancer/neoplasm/tumor/carcinoma＂, ＂polymorphism＂（An upper date limit of October, 31, 2009）. A meta-analysis was performed to evaluate the relationship among XPA, XPC and XPD polymorphism and lung cancer risks. Results： A total of 31 publications retrieved from Pubmed and Embase included in this study. XPC A939C CC genotype increased lung cancer risk in total population （recessive genetic model： OR=1.23, 95% CI：1.05-1.44; homozygote comparison： OR=1.21,95%CI：1.02-1.43and CC vs. CA contrast： OR=1.25,95%CI：1.06-1.48）, except in Asians. XPD A751C, 751C allele and CC genotype also increased lung cancer risk in total population and in Caucasians （recessive genetic model： Total population： OR=1.20, 95%CI：1.07-1.35）. No significant correlation was found between XPD A751C and lung cancer risk in Asians and African Americans. XPD G312A AA genotype increased lung cancer risk in total population, in Asians and Caucasians（recessive genetic model： Total population： OR=1.20, 95%CI： 1.06-1.36）. No significant association was found between XPA G23A, XPC C499T, XPD C156A and lung cancer risk. Conclusion： Our results suggest that the polymorphisms in XPC and XPD involve in lung cancer risks. XPA polymorphisms is less related to lung cancer risk.

关键词： nucleotide excision repair Polymorphism Lung cancer Meta-analysis

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DNA repair Gene Polymorphisms in the nucleotide excision repair Pathway and Lung Cancer Risk:A Meta-analysis

DNA Repair Gene Polymorphisms in the Nucleotide Excision Rep...

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2012贵州省医学会胸心血管外科年会

作者： Meng Luo Chengwu Liu Di Liu Hong Mei Qinghua Zhou

Objective:A number of studies have reported the association of "XPA","XPC","XPD/ERCC2" gene polymorphisms with lung cancer ***,the results were *** clarify the impact of polymorphisms of "XPA","XPC","XPD/ERCC2",on lung cancer risk,a meta-analysis was performed in this study. Methods:The electronic databases PubMed and Embase were retrieved for studies included in this meta-analysis by "XPA","XPC","XPD/ERCC2","lung","cancer/neoplasm/tumor/carcinoma", "polymorphism"(An upper date limit of October,31,2009).A meta-analysis was performed to evaluate the relationship among XPA,XPC and XPD polymorphism and lung cancer risks. Results:A total of 31 publications retrieved from Pubmed and Embase included in this *** A939C CC genotype increased lung cancer risk in total population(recessive genetic model:OR=1.23,95%CI:1.05-1.44;homozygote comparison:OR=1.21,95%CI:1.02-1.43and CC *** contrast:OR=1.25,95%CI:1.06-1.48), except in *** A751C,751C allele and CC genotype also increased lung cancer risk in total population and in Caucasians(recessive genetic model:Total population:OR=1.20,95%CI:1.07-1.35).No significant correlation was found between XPD A751C and lung cancer risk in Asians and African *** G312A AA genotype increased lung cancer risk in total population,in Asians and Caucasians(recessive genetic model:Total population:OR=1.20,95%CI:1.06-1.36).No significant association was found between XPA G23A,XPC C499T,XPD C156A and lung cancer risk. Conclusion:Our results suggest that the polymorphisms in XPC and XPD involve in lung cancer *** polymorphisms is less related to lung cancer risk.

关键词： nucleotide excision repair Polymorphism Lung cancer Meta-analysis

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Protective effects of Rad23 protein on ultraviolet damage to HeLa cells

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Journal of Central South University 2013年第11期20卷 2974-2980页

作者：李秀山张继红赵小英刘选明 State Key Laboratory of Chemo/Biosensiny and Chemometrics (Bioenergy and Biomaterial Research Center College of BiologyHunan University)

Protein Rad23, a nucleotide excision repair factor, mainly involves in repairing the DNA damage from environment, such as UV light. The function of Rad23 protein involved in DNA damage repair from many environmental factors has been studied extensively, but it is not clear from ultraviolet irradiation. To further investigate the photo-protective function of Rad23 protein on HeLa cells damaged from UV light irradiation, firstly, HeLa cells were irradiated by UV light and incubated with the fusion protein of pCold-Rad23, then the cell viability and apoptosis rate were detected by MTT and Hoechst33342/Pl fluorescent staining, respectively. The results show that the recombinant Rad23 protein can protect the HeLa cells from UV irradiation, and inhibit the apoptosis of HeLa cell by UV irradiation.

关键词： Rad23 protein nucleotide excision repair HeLa cell injury

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Formation and repair of DNA-protein crosslink damage

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Science China(Life Sciences) 2017年第10期60卷 1065-1076页

作者： Naeh L.Klages-Mundt Lei Li Department of Experimental Radiation Oncology The University of Texas MD Anderson Cancer Center Houston TX 77030 USA Program in Genetics and Epigenetics The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Houston TX 77030 USA

DNA is constantly exposed to a wide array of genotoxic agents, generating a variety of forms of DNA damage. DNA-protein crosslinks(DPCs)—the covalent linkage of proteins with a DNA strand—are one of the most deleterious and understudied forms of DNA damage, posing as steric blockades to transcription and replication. If not properly repaired, these lesions can lead to mutations, genomic instability, and cell death. DPCs can be induced endogenously or through environmental carcinogens and chemotherapeutic agents. Endogenously, DPCs are commonly derived through reactions with aldehydes, as well as through trapping of various enzymatic intermediates onto the DNA. Proteolytic cleavage of the protein moiety of a DPC is a general strategy for removing the lesion. This can be accomplished through a DPC-specific protease and and/or proteasome-mediated *** excision repair and homologous recombination are each involved in repairing DPCs, with their respective roles likely dependent on the nature and size of the adduct. The Fanconi anemia pathway may also have a role in processing DPC repair intermediates. In this review, we discuss how these lesions are formed, strategies and mechanisms for their removal, and diseases associated with defective DPC repair.

关键词： DNA-protein crosslinks nucleotide excision repair SPRTN Fanconi anemia

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How two helicases work together within the TFIIH complex, a perspective from structural studies of XPB and XPD helicases

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Frontiers in Biology 2013年第4期8卷 363-368页

作者： Li FAN Department of Biochemistry University of California at Riverside Riverside CA 92521 USA

Xeroderma pigmentosum group B （XPB） and D （XPD） are two DNA helicases inside the transcription factor TFIIH complex required for both transcription and DNA repair. The importance of these helicases is underscored by the fact that mutations of XPB and XPD cause diseases with extremely high sensitivity to UV-light and high risk of cancer, premature aging, etc. This mini-review focuses on recent developments in both structural and functional characterization of these XP heficases to illustrate their distinguished biological roles within the architectural restriction of the TFIIH complex. In particular, molecular mechanisms of DNA unwinding by these helicases for promoter opening during transcription initiation and bubble-creation around the lesion during DNA repair are described based on the integration of the crystal structures of XPB and XPD helicases into the architecture of the TFIIH complex.

关键词： XPB XPD TFIIH helicase DNA repair nucleotide excision repair Wanscription

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Pharmacogenomics of Cisplatin Sensitivity in Non-small Cell Lung Cancer

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Genomics, Proteomics & Bioinformatics 2014年第5期12卷 198-209页

作者： Maimon C.Rose Elina Kostyanovskaya R.Stephanie Huang Biological Sciences Division University of Chicago Department of Medicine University of Chicago

Cisplatin, a platinum-based chemotherapeutic drug, has been used for over 30 years in a wide variety of cancers with varying degrees of success. In particular, cisplatin has been used to treat late stage non-small cell lung cancer （NSCLC） as the standard of care. However, therapeutic outcomes vary from patient to patient. Considerable efforts have been invested to identify biomark- ers that can be used to predict cisplatin sensitivity in NSCLC. Here we reviewed current evidence for cisplatin sensitivity biomarkers in NSCLC. We focused on several key pathways, including nucleotide excision repair, drug transport and metabolism. Both expression and germline DNA variation were evaluated in these key pathways. Current evidence suggests that cisplatin-based treatment could be improved by the use of these biomarkers.

关键词： Cisplatin Non-small cell lung cancer Biomarker nucleotide excision repair Copper transport Glutathione S-transferase

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Molecular basis of eIF3a action in therapeutic response of lung cancer patients to platinum-based chemotherapy

Molecular basis of eIF3a action in therapeutic response of l...

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中国药理学会第十一次全国学术会议

作者： YIN Ji-ye~(1,2),SHEN Jie~1,DONG Zi-zheng~2,HUANG Qiong~1,ZHONG Mei-zuo~3, FENG De-yun~4,ZHOU Hong-hao~1,ZHANG Jian-ting~2,LIU Zhao-qian~1 (1.Institute of Clinical Pharmacology,Hunan Key Laboratory of Pharmacogenetics,Central South University, Changsha,Hunan 410078,China 2.Department of Pharmacology and Toxicology,IU Simon Cancer Center,Indiana University School of Medicine,Indianapolis,Indiana 46202,USA 3.Department of Oncology,Xiang-Ya Hospital,Central South University,Changsha 410008,China 4.Department of Pathology,Xiang-Ya Hospital,Central South University,Changsha 410008,China)

eIF3a is the largest subunit of eukaryotic translation initiation factor 3(eIF3) that has been suggested to play a role in translational control of gene expression and in cell proliferation as well as in *** this study,we tested the hypothesis that eIF3a may regulate the expression of DNA repair proteins which in turn affects response of lung cancer patients to treatments by DNA-damaging anticancer *** found that eIF3a expression in cancers correlates inversely with response of lung cancer patients to platinum -based *** down or ectopic over-expressing eIF3a in cell lines increased and decreased cellular resistance to cisplatin as well as anthrocycline anticancer drugs,*** investigation showed that eIF3a regulates the expression of NER proteins and NER activity which likely mediates the effect of eIF3a on cellular response to DNA-damaging anticancer drugs.

关键词： DNA repair drug resistance eIF3a nucleotide excision repair platinum

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