Impact of ERCC2 Gene Polymorphisms on OSCC Susceptibility and Clinical Characteristics.
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ABSTRACT:
SUBMITTER: Tejasvi MA
PROVIDER: S-EPMC7938941 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND The objective of this study was to detect the association between ERCC excision repair 2, TFIIH core complex helicase subunit (ERCC2) gene polymorphisms and diffuse large B-cell lymphoma (DLBCL) susceptibility. MATERIAL AND METHODS This study used a case-control design. ERCC2 gene rs1799793 (Asp312Asn) and rs13181 (Lys751Gln) polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) both in DLBCL patients and healthy controls. The association between ERCC2 gene polymorphisms and DLBCL risk was assessed by χ² test. Odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were used to address the association strength. Subgroup analyses were also performed to investigate the genetic effects of ERCC2 polymorphisms on clinical characteristics of DLBCL patients. RESULTS A significant association was discovered between the rs1799793 A allele and increased DLBCL risk (P=0.031, OR=1.928, 95% CI=1.052-3.534). The C allele of rs13181 was obviously associated with elevated DLBCL susceptibility (P=0.047, OR=1.820, 95% CI=1.002-3.305). The subgroup analysis demonstrated that rs1799793 and rs13181 polymorphisms had no relationship with serum lactate dehydrogenase level, nidus number, B-symptoms, Ann Arbor stages, or immunological types in DLBCL cases (P>0.05 for all). CONCLUSIONS Minor allele carriers of ERCC2 gene rs1799793 (Asp312Asn) and rs13181 (Lys751Gln) polymorphisms had higher susceptibility to DLBCL.
| S-EPMC6179170 | biostudies-literature
Project description:Studies have investigated the relationship between XPD Lys751Gln and Asp312Asn genetic variants and risk of cutaneous basal cell carcinoma (BCC). However, the results remain inconclusive. We performed a meta-analysis, using a comprehensive strategy based on the allele model and a model-free approach, to investigate the association of between XPD Lys751Gln and Asp312Asn polymorphisms with BCC risk. For XPD Lys751Gln, no significant BCC risk was found in the allele model (OR = 0.97, 95% CI 0.90-1.04, I (2) = 35.3%, P heterogeneity = 0.125) and with model-free approach (ORG = 0.95, 95% CI 0.87-1.04, I (2) = 15.9%, P heterogeneity = 0.296). For XPD Asp312Asn, there was also no association between this polymorphism and BCC risk in the allele model (OR = 0.94, 95% CI 0.86-1.03, I (2) = 0, P heterogeneity = 0.650) and with the model-free approach (ORG = 0.94, 95% CI 0.85-1.05, I (2) = 0, P heterogeneity = 0.603). Therefore, this meta-analysis suggests that the XPD Lys751Gln and Asp312Asn polymorphisms were not associated with BCC risk. Further large and well-designed studies are needed to confirm these findings.
| S-EPMC4565234 | biostudies-literature
Project description:A disintegrin and metalloprotease (ADAM) family proteins are type-I transmembrane glycoproteins with multiple functions in cell adhesion, migration, proteolysis and signaling. ADAM10 is a member of the ADAM family reportedly involved in cancer progression and has been shown to be overexpressed in hepatocellular carcinoma (HCC) tissues and significantly associated with tumor progression and shortened survival. This study investigated ADAM10's single nucleotide polymorphisms (SNPs) and their association to HCC development and regulation. Real-time polymerase chain reaction was used to analyze five SNPs of ADAM10 in 333 patients with HCC and 1196 controls without cancer. The results indicated that of the 333 patients with HCC, those who carried ADAM10 rs514049 (AC + CC) variants had a higher risk of developing lymph node metastasis (odds ratio [OR] = 5.087, p = 0.027), and those who carried ADAM10 rs653765 (GA + AA) variants had a higher risk of developing distant metastasis (OR = 3.346, p = 0.020) and higher levels of ?-fetoprotein. In conclusion, our study demonstrated that the SNPs of ADAM10 are involved in HCC progression. ADAM10 SNPs may be used as therapeutic targets to evaluate poor prognoses for HCC.
| S-EPMC6158669 | biostudies-literature
Project description:Urothelial cell carcinoma (UCC) is the commonest malignant tumor of the urinary tract and the second most common kidney cancer malignancy. Growth arrest-specific 5 (GAS5), a long noncoding RNA, is encoded by the GAS5 gene and plays a critical role in cellular growth arrest and apoptosis. In the current study, two single nucleotide polymorphisms (SNPs) in the GAS5 gene, rs145204276 and rs55829688, were selected to investigate correlations between these single SNPs and susceptibility to UCC. A total of 430 UCC cases and 860 ethnically matched healthy controls were included. SNP rs145204276 and SNP rs55829688 were determined using a TaqMan genotyping assay. Logistic regression models demonstrated that female patients with UCC carrying the rs145204276 GAS5 Ins/Del or Del/Del genotype had a 3.037-fold higher risk of larger tumor status (95% confidence interval 1.259-7.324) than did rs145204276 wild type (Ins/Ins) carriers (p = 0.011). The Cancer Genome Atlas validation cohort analysis demonstrated that the expression of GAS5 in female patients with bladder urothelial carcinoma (BLCA) with larger tumor size was much lower than that in patients with a smaller tumor size (p = 0.041). Kaplan-Meier curve analysis and the log-rank test revealed that female patients with BLCA and lower GAS5 expression had poorer overall survival than those with higher GAS5 expression. In conclusion, genetic variations in GAS5 rs145204276 may serve as a critical predictor of the clinical status of female patients with UCC.
| S-EPMC7277236 | biostudies-literature
Project description:In Taiwan, oral cancer has causally been associated with environmental carcinogens. CCL4 (C-C chemokine ligand 4), a macrophage inflammatory protein with a key role in inflammation and immune-regulation, was implicated in carcinogenesis by facilitating instability in the tumor environment. The purpose of this study was to identify gene polymorphisms of CCL4 specific to patients with oral squamous cell carcinoma (OSCC) susceptibility and clinicopathological characteristics. A total of 2,053 participants, including 1192 healthy people and 861 patients with oral cancer, were recruited for this study. Three single-nucleotide polymorphisms (SNPs) of the CCL4 gene were analyzed by a real-time PCR. We found that the T/T homozygotes of CCL4 rs1634507 G/T polymorphism and the GG haplotype of 2 CCL4 SNPs (rs1634507 and rs10491121) combined were associated with oral-cancer susceptibility. In addition, TA haplotype significantly decreased the risks for oral cancer by 0.118 fold. Among 1420 smokers, CCL4 polymorphisms carriers with the betel-nut chewing habit had a 15.476-20.247-fold greater risk of having oral cancer compared to CCL4 wild-type (WT) carriers without the betel-nut chewing habit. Finally, patients with oral cancer who had A/G heterozygotes of CCL4 rs10491121 A/G polymorphism showed a lower risk for an advanced tumor size (> T2) (p=0.046), compared to those patients with AA homozygotes. Our results suggest that the CCL4 rs1634507 SNP have potential predictive significance in oral carcinogenesis. Gene-environment interactions of CCL4 polymorphisms might influence oral-cancer susceptibility. CCL4 rs10491121 may be a factor to predict the tumor size in OSCC patients.
| S-EPMC5458219 | biostudies-literature
Project description:We investigated the correlation between type 2 diabetes (T2D)-related genes and the clinical characteristics of T2D in the Chinese Han population. Our study included 319 patients and 387 controls. Age, gender, clinical features, medications intake and biochemical blood profiles were analyzed. Genotyping was performed on a total of 18 single nucleotide polymorphisms previously reported to be associated with T2D. Our analyses revealed that the CT genotype of ARHGAP22 rs4838605 is associated with T2D risk. Upon analyzing the subjects' clinical characteristics, we found that for rs2811893, the TT genotype correlated with high creatinine levels, while the AA genotype of rs17045754 and the TT genotype of rs4838605 correlated with elevated triglyceride levels. In addition, the AA genotype of rs17376456 and the TT genotype of rs6214 (p = 0.006) correlated with elevated hemoglobin A1c levels. Lastly, those carrying the TT genotype of rs7772697 and the CA genotype of rs3918227 exhibited higher mean body mass index and Cystatin C than controls. Our results showing that the ARHGAP22 gene is associated with an increased risk of T2D, and that seven SNPs in MYSM1, PLXDC2, ARHGAP22 and HS6ST3 promote T2D progression and could help predict the clinical course of T2D in patients at risk.
| S-EPMC5356749 | biostudies-literature
Project description:Background & Aims Variants in the tumor necrosis factor superfamily member 15 gene (TNFSF15, also called TL1A) have been associated with risk for inflammatory bowel diseases (IBD). TL1A affects expression of multiple cytokines to promote mucosal inflammation. Little is known about the TL1A-response pathways that regulate cytokine expression. We investigated T-cell gene expression patterns to determine the mechanisms by which TL1A regulates cytokine production, and whether these associate with outcomes of patients with Crohn’s disease (CD).Methods Peripheral T cells isolated from normal donors were cultured with TL1A. We performed gene expression profile analysis, by RNA sequencing, of subsets of interferon gamma (IFNG)-producing and non-producing cells, purified by flow cytometry. Unsupervised hierarchical clustering analysis was used to identify gene expression differences between these subsets. Ribonuclease T2 gene (RNASET2) expression and methylation were assessed by quantitative trait loci analyses. Clinical characteristics of patients (complications, resistance to therapy, recurrence time) were associated with single nucleotide polymorphisms in RNASET2. We performed motif screening to identify polymorphisms that disrupt transcription factor binding sites. Levels of RNASET2 were knocked down with small interfering RNA in CD4+ T cells and the effect on protein expression was determined by proteomic analysis and cytokine production. Cell aggregation was measured by flow cytometry. ResultsWe identified 764 genes with at least a 2-fold difference in TL1A-mediated expression between IFNG-secreting and non-secreting T cells (P<1 × 10−5). Many of these genes were located near IBD susceptibility variants. RNASET2 was the only IBD risk-associated gene with greater than 5-fold downregulation in the IFNG-secreting subset. RNASET2 disease risk variants were associated with decreased expression in peripheral and mucosal tissues and DNA hypermethylation in CD patients requiring surgical intervention. RNASET2 disease risk variants were associated in CD patients with more complicated disease or resistance to therapy, defined in part by failed response to treatment, increased length of intestinal resection, shorter time to repeat surgery, and high Rutgeerts score (>2) in post-operative endoscopy. The RNASET2 variant rs2149092 was predicted to disrupt a consensus binding site for the transcription factor ETS within an enhancer region. Expression of RNASET2 correlated with expression of ETS. RNASET2 knockdown in T cells increased expression of IFNG and ICAM1 and induced T cells aggregation. A blocking antibody against LFA1, disrupting the LFA1-ICAM1 interaction, reduced T-cell production of IFNG. Conclusions We identified decreased expression of RNASET2 as a component of TL1A-mediated increase in production of IFNG and as a potential biomarker for patients with severe CD. Further study of the role of RNASET2 in regulating mucosal inflammation may lead to development of novel therapeutic targets.
2022-10-11 | GSE215144 | GEO
Project description:An increasing number of studies have explored genetic associations between the functionally important polymorphisms in estrogen receptor 1 (ESR1) gene and migraine susceptibility. The previously reported associations have nevertheless been inconsistent.The present work incorporating the published data derived from 8 publications was performed to assess the impact of these polymorphisms on incident migraine. Strength of the genetic risk was estimated by means of an odds ratio along with the 95% confidence interval (OR and 95% CI).From the results, we found individuals who harbored the 325-GG genotype, compared with those harboring the CC genotype or CG and CC combined genotypes, had almost 50% greater risk of migraine. The same genetic models showed notable associations in subgroups of Caucasians and migraine with aura (MA). For 594G>A, a moderately increased risk of migraine was seen under AG versus GG. The AA + AG versus GG model, however, showed a borderline association with migraine. Subgroup analyses according to ethnicity and subtype of migraine provided statistical evidence of significantly increased risk of migraine in Caucasians and of a marginal association with MA, respectively. Both 325C>G and 594G>A polymorphisms showed no major effects either in males or in females.Based on the statistical data, we conclude some of the ESR1 gene polymorphisms may have major contributions to the pathogenesis of migraine in Caucasian populations.
| S-EPMC4616512 | biostudies-literature
Project description:Breast and ovarian cancers increased in the last decades. Except rare cases with a genetic predisposition and high penetrance, these pathologies are viewed as a polygenic disease. In this concept, association studies look for genetic variations such as polymorphisms in low penetrance genes, i.e. genes in interaction with environmental factors. DNA repair systems that protect the genome from deleterious endogenous and exogenous damages have been shown to have significantly reduced. In particular, enzymes of the nucleotide excision repair pathway are suspected to be implicated in cancer. In this study, 2 functional polymorphisms in a DNA repair gene ERCC2 were analyzed. The population included 911 breast cancer cases, 51 ovarian cancer cases and 1000 controls. The genotyping of 2 SNP (Single Nucleotide Polymorphism) was carried out on the population with the MGB (Minor Groove Binder) probe technique which consists of the use of the allelic discrimination with the Taqman method. This study enabled us to show an increase in risk of breast cancer with no oral contraceptive users and with women exhibiting a waist-to-hip ratio (WHR) > 0.85 for Asn homozygous for ERCC2 312.
| S-EPMC2394522 | biostudies-literature
Project description:BACKGROUND:Coronary artery disease (CAD) was the second leading cause of death for the past 3 years in Taiwan. The insulin-like growth factor (IGF) system is considered a new risk factor of CAD because investigations show that the levels and bioactivity of IGF-I and IGFBP-3 (where IGFBP is insulin-like growth factor-binding protein) may be involved in elevating the risk of CAD. This study investigated the relationships among IGF-I +1770, IGF-I +6093, and IGFBP-3 -202 genetic polymorphisms and CAD in the Taiwanese population. METHODS:A total of 581 subjects, including 390 non-CAD controls and 191 patients with CAD, were recruited and the isolated DNA was subjected to real-time polymerase chain to evaluate the effects of these three polymorphic variants on CAD. RESULTS:Our results showed a significant association between the IGF-I +1770 gene polymorphism and increased risk of CAD. Furthermore, CAD patients with a minimum of one mutant C allele, T/C or C/C, in IGF-I +1770 gene polymorphism had significantly high blood pressure including systolic blood pressure (SBP; P = 0.025) and diastolic blood pressure (DBP; P = 0.004), compared to CAD patients with T/T homozygotes. Moreover, CAD patients with a minimum of one mutant A allele, G/A or A/A, in the IGF-I +6093 gene polymorphism had a 1.695-fold elevated risk of congestive heart failure (CHF), compared to CAD patients with the G/G homozygote. CONCLUSIONS:Polymorphism of IGF-I +1770 was associated with increased CAD risk. In CAD patients, the contributions of IGF-I +1770 and +6093 could be through the effect on blood pressure in CAD patients.
| S-EPMC6807539 | biostudies-literature