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

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 investigation.This study aimed to evaluate the relationship between NER gene polymorphisms and the risk of hepatoblastoma in Eastern Chinese Han children.Methods: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 XPG.Then,multivariate logistic regression analysis was performed,and odds ratios(ORs)and 95%confidence intervals(95%CIs)were utilized to assess the strength of associations.Results:Three SNPs were related to hepatoblastoma risk.XPC 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 subgroups.Moreover,there was evidence of functional implications of these significant SNPs suggested by online expression quantitative trait loci(eQTLs)and splicing quantitative trait loci(sQTLs)analysis.Conclusions: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.

Nucleotide Contribution to the Functioning of SERT, Na /K ATPase and GPCR Proteins

Purine nucleotides are crucial for the effective operation of cell membrane proteins maintaining the neurotransmitter responses of 5-HT. Major protein targets in the treatment of depression include SERT, N/K ATPase and GPCR. Each protein target is responsive to a specific complement of drugs: antidepressants (SERT), lithium and cardiogenic steroids (N/K ATPase), 5-HT receptor ligands (GPCR). Computational software is useful for comparing molecular similarity within ligand-ligand and ligand-nucleotide structures. Previous studies demonstrate that GPCR ligands of different pharmacologic classes display relative molecular similarity to nucleotide structures. The current study applies this methodology to compound structures modulating SERT and N/K ATPase receptors. Minimum energy conformers of SERT antagonists demonstrate relative molecular similarity to the structural template of GTP nucleotide. GTP template fits of 5-HT and psilocin are similar, whereas a SERT-like fit is one of several for the ketamine structure. Endogenous and pharmaceutical modulators of Na/K ATPase relate to adenine nucleotide. The fits of cardiogenic steroids to a cGMP template demonstrate similarities and differences between compounds. Relative molecular similarity within the structures of hormones, drugs and nucleotides has implications for neurotransmitter transport and cell signal transduction processes.

Impact of cognition-related single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease

Multiple single nucleotide polymorphisms may contribute to cognitive decline in Parkinson’s disease. However, the mechanism by which these single nucleotide polymorphisms modify brain imaging phenotype remains unclear. The aim of this study was to investigate the potential effects of multiple single nucleotide polymorphisms on brain imaging phenotype in Parkinson’s disease. Forty-eight Parkinson’s disease patients and 39 matched healthy controls underwent genotyping and 7 T magnetic resonance imaging. A cognitive-weighted polygenic risk score model was designed, in which the effect sizes were determined individually for 36 single nucleotide polymorphisms. The correlations between polygenic risk score, neuroimaging features, and clinical data were analyzed. Furthermore, individual single nucleotide polymorphism analysis was performed to explore the main effects of genotypes and their interactive effects with Parkinson’s disease diagnosis. We found that, in Parkinson’s disease, the polygenic risk score was correlated with the neural activity of the hippocampus, parahippocampus, and fusiform gyrus, and with hippocampal-prefrontal and fusiform-temporal connectivity, as well as with gray matter alterations in the orbitofrontal cortex. In addition, we found that single nucleotide polymorphisms in α-synuclein(SNCA) were associated with white matter microstructural changes in the superior corona radiata, corpus callosum, and external capsule. A single nucleotide polymorphism in catechol-O-methyltransferase was associated with the neural activities of the lingual, fusiform, and occipital gyri, which are involved in visual cognitive dysfunction. Furthermore, DRD3 was associated with frontal and temporal lobe function and structure. In conclusion, imaging genetics is useful for providing a better understanding of the genetic pathways involved in the pathophysiologic processes underlying Parkinson’s disease. This study provides evidence of an association between genetic factors, cognitive functions, and multi-modality neuroimaging biomarkers in Parkinson’s disease.

Electrochemical Biosensor for Detection of Staphylococcus aureus Based on Nucleic Acid Aptamers

Staphylococcus aureus is a gram-staining positive cocci bacillus baterium and also one of the foodborne pathogens, which is a serious potential hazard to human health and food safety. We constructed an electrochemical biosensor for the detection of S. aureus based on nucleic acid aptamers to achieve highly specific detection of S. aureus. The detection of S. aureus was realized by using Aptamer (Apt) to capture S. aureus, which resulted in a change in the spatial conformation of Apt and a decrease in the electrochemical signal. Under the optimized experimental conditions, the detected electrochemical signals were positively correlated with the concentration of S. aureus with a linear range of 1 × 101 - 1 × 105 CFU/mL, a detection limit of 4.76 CFU/mL, and an experimental recovery of 97.43% - 99.37%. Therefore, we successfully constructed an electrochemical biosensor for the specific detection of S. aureus, which has the advantages of high specificity, sensitive detection and convenient operation.

Recognition mechanism and sequence optimization of organophosphorus pesticides aptamers for better monitoring contaminations in food

Aptamers as a kind of biological recognition element have shown great potential in monitoring and the rapid quantification of organophosphorus pesticides(OPPs). However, molecules of OPPs are structurally similar and original aptamers selected by systematic evolution of ligands by exponential enrichment are usually long-chain bases, which hamper the further application under OPPs-aptamer recognition. The aim of the research was to develop a new strategy to design oligonucleotide sequences for binding OPPs by combination of experimental and molecular modeling methods. 3D models of aptamers binding OPPs were constructed, and binding energy and the most probable binding site for the OPPs were then determined by molecular docking, and the binding sites were further confirmed by the results of 2-AP replaced experiments. Based on the docking results, a new aptamer for detection 4 representative OPPs with only 29 bases was designed by reasonable truncation and mutation of the reported aptamer(named S4-29). The interaction between this new aptamer and OPPs were analyzed by molecular docking, microscale thermophoresis, circular dichroism and fluorometric analysis. The results revealed that the new aptamer exhibit more superior recognition performance to OPPs, which can be promote the monitoring ability of OPPs contaminations in food.

Analysis on the Relationship between Selective Pressure and Nucleotide Substitution Rate in Nucleus and Organelle Genes of Sorghum and Maize

[Objective]The aim was to research the relationship between nucleotide substitutions rate and selective pressure.[Method]Synonymous and nonsynonymous substitutions and their ratios for some sorghum and maize genes in nucleus and organelle genomes were analyzed by statistical method,and comparative analysis of related functional genes were carried out.[Result]The pure selective pressures of the related functional genes were similar between nucleus and chloroplast genomes,but was lower in mitochondrial genome.The significant differences of nucleotide substitution rate between sorghum and maize orthologous genes in nucleus genome,and among different functional genes in nucleus genome were mainly due to the nonsynonymous substitution difference.[Conclusion]The molecular evolutional rate of different functional genes and different lineages were influenced by selective pressure.The differences of molecular evolutional rate among nucleus,chloroplast and mitochondria genomes had no direct relationship with selective pressure.

Influence of a nucleotide oligomerization domain 1 (NOD1) polymorphism and NOD2 mutant alleles on Crohn's disease phenotype

AIM： To examine genetic variation of nucleotide oligomerization domain 1 （NOD/） and NOD2, their respective influences on Crohn＇s disease phenotype and gene-gene interactions. METHODS： （ND1＋32656＊1） NOD1 polymorphism and SNPS, SNP12 and SNP13 of NOD2 were analyzed in 97 patients and 50 controls. NOD2 variants were determined by reaction restriction fragment length polymorphism analysis. NOD1 genotyping and NOD2 variant confirmation were performed by specific amplification and sequencing. RESULTS： The distribution of NOD1 polymorphism in patients was different from controls （P = 0.045） and not altered by existence of NOD2 mutations. In this cohort, 30.92% patients and 6% controls carried at least one NOD2 variant （P 〈 0.001） with R702W being the most frequent variant. Presence of at least one NOD2 mutation was inversely associated with colon involvement （9.09% with colon vs 36.4% with ileal or ileocolonic involvement, P = 0.04） and indicative of risk of penetrating disease （52.63% with penetrating vs 25.64% with non-penetrating or stricturing behavior, P = 0.02）. L1007finsC and double NOD2 mutation conferred the highest risk for severity of disease （26.3% with penetrating disease vs 3.8% with non-penetrating or stricturing behavior presented L1007finsC, P = 0.01 and 21.0% with penetrating disease vs 2.5% with non-penentrating or stricturing behavior carried double NOD2 mutation, P = 0.007）. Exclusion of patients with NOD2 mutations from phenotype/NODl-genotype analysis revealed higher prevalence of ＊1＊1 genotype in groups of younger age at onset and colonic location.CONCLUSION： This study suggests population differences in the inheritance of risk NOD1 polymorphism and NOD2 mutations. Although no interaction between NOD1-NOD2 was noticed, a relationship between disease location and Nod-like receptor molecules was established.

Single Nucleotide Polymorphism Analysis on 5' Regulatory Region of Goose Insulin-like Growth FactorⅠGene

[ Objedive] This study was aimed to determine the single nucleotide polymorphisms （SNPs） of IGF-I gene in two breeds, Wanxi white goose and Langde goose. [ Method] Two pair of primers was designed based on chicken and porcine genomic sequence to amplify the 5＇ regulatory region of IGF-I, and the sequence was determined and analyzed. [ Result] A total of four SNPs were identified in this region by PCR-SSCP meth- od, that is, A to T at 26 nt, A to G at 215 nt, A to G at 314 nt, and A to T at 325 nt. [ Conclusioa] The two breeds ,wanxi white geese and Langde geese, agree with Hardy-weinberg equilibrium with respect to these SNPS.

Separation of Nucleotides in Swine Tissues Using Capillary Zone Electrophoresis

Capillary zone electrophoresis has been applied to the analysis of nucleotides. The effects of buffer concentration. pH and other operating conditions on the separation were investigated and optimized. By using the method, separation and identification of nuclotides in swine tissues were completed.

Single nucleotide polymorphism C677T in the methylenetetrahydrofolate reductase gene might be a genetic risk factor for infertility for Chinese men with azoospermia or severe oligozoospermia

Aim： To analyze the distribution of the single nucleotide polymorphism （SNP） C677T in the methylenetetrahydrofolate reductase （MTHFR） gene in 355 infertile Chinese patients with idiopathic azoospermia or severe oligozoospermia and 252 fertile Chinese men as controls to explore the possible association of the SNP and male infertility. Methods： Using the polymerase chain reaction （PCR）-restriction fragment length polymorphism technique, the allele and genotype distribution of SNP C677T in the MTHFR gene were investigated in both patients and controls. Results： The frequencies of allele T （40.9% vs 30.4%, P = 0.002, odds ration [OR] = 1.58, 95% confidence interval [CI]： 1.24-2.02） and mutant homozygote （TT） （18.3% vs. 11.5%, P = 0.023, OR = 1.72, 95% CI： 1.07-2.76） as well as carrier with allele （TT ＋ CT） （63.4% vs. 49.2%, P = 0.0005, OR = 1.79, 95% CI： 1.29-2.48） in infertile patients were significantly higher than those in controls. After patient stratification, the significant differences in distribution of the SNP between each patient subgroup and control group still remained. Conclusion： Our findings indicate that there is an association of SNP C677T in the MTHFR gene with male infertility, suggesting that this polymorphism might be a genetic risk factor for male infertility in Chinese men.

Identification of a Regulatory Single Nucleotide Polymorphism in the Adiponectin (APM1) Gene Associated with Type 2 Diabetes in Han Nationality

Objective To identify the genetic defects of the the adiponectin （APM1） gene that contribute to the development of type 2 diabetes （T2DM） and determine the functional single nucleotide polymorphisms （SNPs） in the APMI gene associated with T2DM in Han nationality. Methods The APMI gene 5＇-UTR was screened by direct sequencing to identify common polymorphisms. Identified SNPs were genotyped in 585 nondiabetic controls, 278 subjects with impaired glucose intolerance （IGT） and 212 patients with T2DM. The functions of SNPs in the regulatory region were assessed by reporter gene assay. Possible association between SNPs and plasma APMI levels or metabolic parameters was statistically asses,sed. Results Three SNPs were identified in the APMI gene 5＇-UTR. A case-control study revealed that SNP -11377 G/C had significant differences in allele frequencies between T2DM patients and nondiabetic controls （G 0.314/C 0.686 vs. G 0.265/C 0.735, P=0.03）. Haplotype analysis of three SNPs in the APM1 gene showed that no significant association of haplotypes with T2DM. IGT was detected in the present study. Reporter gene assay showed that SNP did not influence the transcription efficiency in the 3T3-LI cell line. Conclusion SNP - 11377 G/C in the proximal promoter region of the APM 1 gene contributes to the development of T2DM in Han nationality but may not be a functional SNP in the APM1 gene.

Expression analysis,single nucleotide polymorphisms within SIRT4 and SIRT7 genes and their association with body size and meat quality traits in Qinchuan cattle

Silent information regulator 2 （Sir2） proteins, or sirtuins, are nicotine adenine dinucleotide （NAD）-dependent deacetylases that connect metabolism with longevity in lower organisms. In mammals, there are seven Sir2 homologs, namely, silent information regulators （SIRT1-7）. SIRT4 and SIRT7 genes play a crucial role in regulating lipid metabolism, cellular growth and metabolism. This suggests that they are potential candidate genes for affecting body size and meat quality traits in animals. Hence, this study aimed to detect genetic variations of both SIRT4 and SIRT7 bovine genes in Qinchuan cattle, and to evaluate the effect of these variations on economically important body size and meat quality traits. Expression analysis using quantitative real-time PCR （qPCR） indicated that SIRT4 and SIRT7 were broadly expressed in all thirteen studied tissues. The expression of SIRT4 was higher in liver, muscle, and in subcutaneous fat tissue. In the case of SIRT7, the expression was higher in lung, abomasum, and subcutaneous fat. Using DNAsequencing, a total of three single nucleotide polymorphisms （SNPs） were identified within SIRT4 and SIRT7 genes in 468 Qinchuan cattle. These included one novel SNP within 3＇ untranslated regions （UTR） of SIRT4 （SNP1： g. 13915A〉G） and two novel synonymous substitutions in SIRT7 （SNP2： g.3587C〉T and SNP3： g.3793T〉C）. Statistical analyses indicated that all three SNPs could significantly influence some body size and meat quality traits in Qinchuan cattle. These novel findings will provide a background for application of bovine SIRT4 and SIRT7 genes in the selection program of Chinese cattle.

Gene-gene,gene-environment,gene-nutrient interactions and single nucleotide polymorphisms of inflammatory cytokines

Inflammation plays a significant role in the etiology of type 2 diabetes mellitus(T2DM).The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury,oxidative stress and beta cell apoptosis in T2 DM.Among the recognized markers are interleukin(IL)-6,IL-1,IL-10,IL-18,tissue necrosis factor-alpha(TNF-α),C-reactive protein,resistin,adiponectin,tissue plasminogen activator,fibrinogen and heptoglobins.Diabetes mellitus has firm genetic and very strong environmental influence; exhibiting a polygenic mode of inheritance.Many single nucleotide polymorphisms(SNPs) in various genes including those of pro and antiinflammatory cytokines have been reported as a risk for T2 DM.Not all the SNPs have been confirmed by unifying results in different studies and wide variations have been reported in various ethnic groups.The inter-ethnic variations can be explained by the fact that gene expression may be regulated by gene-gene,gene-environment and gene-nutrient interactions.This review highlights the impact of these interactions on determining the role of single nucleotide polymorphism of IL-6,TNF-α,resistin and adiponectin in pathogenesis of T2 DM.

Single-nucleotide polymorphisms of matrix metalloproteinases and their inhibitors in gastrointestinal cancer

Matrix metalloproteinases(MMPs) are implicated in cancer development and progression and are associated with prognosis.Single-nucleotide polymorphisms(SNPs) of MMPs,most frequently located in the promoter region of the genes,have been shown to influence cancer susceptibility and/or progression.SNPs of MMP-1,-2,-3,-7,-8,-9,-12,-13 and-21 and of the tissue inhibitor of metalloproteinases(TIMPs) TIMP-1 and TIMP-2 have been studied in digestive tract tumors.The contribution of these polymorphisms to the cancer risk and prognosis of gastrointestinal tumors are reviewed in this paper.

Association of three single nucleotide polymorphisms of ESR1 with breast cancer susceptibility:a meta-analysis

Expression of estrogen receptors is correlated with breast cancer risk,but inconsistent results have been reported.To clarify potential estrogen receptor（ESR）-related breast cancer risk,we analyzed genetic variants of ESR1 in association with breast cancer susceptibility.We performed a meta-analysis to investigate the association between rs2234693,rs1801132,and rs2046210（single nucleotide polymorphisms of ESR1）,and breast cancer risk.Our analysis included 44 case-control studies.For rs2234693,the CC genotype had a higher risk of breast cancer compared to the TT or CT genotype.For rs2046210,the AA,GA,or GA ＋ GG genotype had a much higher risk compared to the GG genotype.No significant association was found for the rs 1801132 polymorphism with breast cancer risk.This meta-analysis demonstrates association between the rs2234693 and rs2046210 polymorphisms of ESR1 and breast cancer risk.The correlation strength between rs2234693 and breast cancer susceptibility differs in subgroup assessment by ethnicity.

Synthesis of Isonucleoside-Incorporated Oligonucleotides and Their Binding Abilities with Complementary Sequences

Aim To synthesize isonucleoside-incorporated oligonucleotides and investigatetheir binding abilities with complementary sequences. Methods The synthesis was performed on DNAsynthesizer, and the binding behavior was investigated by thermal denaturation studies. Results Fourkinds of single isonucleoside containing oligonucleotides were synthesized. The results of thermaldenaturation showed that the existence of isonucleoside decreased the stability of duplex, and theeffect was more obvious when the isonucleoside was in the middle of the sequence. No obviousdifference was observed when 6'-OH of isonucleoside was free or was protected by allyl group.Conclusions The existence of isonucleoside in oli-gonucleotide makes chain twist and decreased thestability of duplex.

Single Nucleotide Polymorphisms (SNPs) Discovery and Linkage Disequilib-rium (LD) in Forest Trees

With completion of the Populus genome sequencing project and the availability of many expressed sequence tags （ESTs） databases in forest trees, attention is now rapidly shifting towards the study of individual genetic variation in natural populations. The most abundant form of genetic variation in many eukaryotic species is represented by single nucleotide polymorphisms （SNPs）, which can account for heritable inter-individual differences in complex phenotypes. Unlike humans, the linkage disequilibrium （LD） rapidly decays within candidate genes in forest trees. Thus, SNPs-based candidate gene association studies are considered to be a most effective approach to dissect the complex quantitative traits in forest trees. The present study demonstrates that LD mapping can be used to identify alleles associated with quantitative traits and suggests that this new approach could be particularly useful for performing breeding programs in forest trees. In this review, we will describe the fundamentals, patterns of SNPs distribution and frequency, summarize recent advances in SNPs discovery and LD and comment on the application of LD in the dissection of complex quantitative traits in forest tress. We also put forward the outlook for future SNPs-based association analysis of quantitative traits in forest trees.

In vitro Selection of DNA Aptamers and Fluorescence-Based Recognition for Rapid Detection Listeria monocytogenes

Aptamers are specific nucleic acid sequences that can bind to a wide range of nucleic acid and non-nucleic acid targets with high affinity and specificity. Nucleic acid aptamers are selected in vitro from single stranded DNA or RNA ligands containing random sequences of up to a few hundred nucleotides. Systematic evolution of ligands by exponential enrichment （SELEX） was used to select and PCR amplify DNA sequences （aptamers） capable of binding to and detecting Listeria monocytogenes, one of the major food-borne pathogens. A simplified affinity separation approach was employed, in which L. monocytogenes in exponential （log） phase of growth was used as the separation target. A fluorescently-labeled aptamer assay scheme was devised for detecting L. monoeytogenes. This report described a novel approach to the detection of L. monocytogenes using DNA aptamers. Aptamers were developed by nine rounds of SELEX. A high affinity aptamer was successfully selected from the initial random DNA pool, and its secondary structure was also investigated. One of aptamers named e01 with the highest affinity was further tested in aptamer-peroxidase and aptamer-fluorescence staining protocols. This study has proved the principle that the whole-cell SELEX could be a promising technique to design aptamer-based molecular probes for dectection of pathogenic microorganisms without tedious isolation and purification of complex markers or targets.

Association between low molecular polypeptide 7 single nucleotide polymorphism and response to therapy in hepatitis C virus infection

AIM: To investigate the relationship between low molecular polypeptide-7 (LMP-7) gene polymorphism and response to interferon (IFN) therapy in chronic hepatitis C virus (HCV) patients. METHODS: LMP-7 polymorphism at codon 49 with nucleotide substitution from A to C was amplified in 104 chronic HCV patients of genotype 4. The amplicons were digested with restriction endonuclease Bsm I and the produced restriction fragment length polymorphism was analyzed. Patients received IFN + regional blood volume therapy for 48 wk and the frequency of thissingle nucleotide polymorphism (SNP) was statistically correlated with treatment response. The exclusion criteria for these patients were stated by the national health program for treating viral hepatitis. Main exclusion criteria included co-infection with hepatitis B virus or schistosomiasis, thyroid dysfunction, uncontrolled diabetes mellitus, history of long term drug or alcohol intake and autoimmune hepatitis. Multivariate analyses were done to correlate LMP-7 SNP plus several factors such as age, gender, weight, serum alpha-fetoprotein (AFP) and alanine aminotransferase levels, liver activity, fibrosis score and viral load with response to therapy. RESULTS: The data presented in this study clearly demonstrated statistically significant differences between sustained virological response (SVR) (defined as the absence of HCV RNA levels in the patient's sera at least 6 mo after discontinuation of treatment) and non-response (NR) (where HCV RNA levels in the patient's sera never become undetectable for 6 mo during or after treatment). Variables were described as odds ratio with 95%CI. The data were considered significant if P values were ≤ 0.05; highly significant if P < 0.01 and very highly significant if P < 0.001. Current data showed that 91.7% of patients carrying LMP-7 C/C allele were associated with SVR, while the other two genotypes C/A and A/A were associated with NR patients, 83.3% and 64.3% respectively, showing that genotype CC was strongly associated with response to interferon (95%CI: 12.0719-134.6572, P = 0.0001). The majority of parameters recorded in SVR and NR patients included higher values of mean age (P = 0.004), alanine aminotransferase (P = 0.001), AFP (P = 0.001), body weight (P = 0.025), viral load (P = 0.025), higher fibrosis and histological activity index indices among NR vs SVR patients. Also, the multivariate statistical analysis of the different factors of fibro-sis score, liver activity grade, genotypes and alleles of LMP-7 gene polymorphism in responders and NRs of HCV patients in this study showed that HCV patients with A allele had a very highly significant association with the NRs, high fibrosis and higher liver activity, while the C allele had a very highly significant association with the responders, low fibrosis and lower liver activity (95%CI: 3.5800-13.2519, P = 0.0001).CONCLUSION: LMP-7 SNP is a candidate gene that should be considered when designing a mathematical model for predicting response to therapy and disease progression in HCV patients.

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

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