Genetic variability of genes in NER pathway influences the treatment outcome of gastric cancer

We performed a study to investigate the role of ERCC1, ERCC2, ERCC5, XPA and XPC polymorphisms from perspective of the whole NER pathway in the prognosis of gastric cancer. A total of 410 gastric cancer patients were recruited between January 2010 and December 2011. Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was used to analyze genotypes of ERCC1 rs11615 and rs3212986, ERCC2 rs13181 and s1799793, ERCC5 rs17655, XPA rs1800975 and XPC rs2228001. Our study found that carriers of ERCC1 rs3212986 TT genotype showed significantly favorable survival than wide-type GG genotype in multivariate analysis (OR=6.38, 95% CI=2.54-19.03), and patients with variant CC genotype of ERCC2 rs13181 exhibited better response to chemotherapy than those with AA genotype (OR=2.21, 95% CI=1.17-4.25). By Cox proportional hazards model, patients with variant TT genotype of ERCC1 rs3212986 exhibited longer PFS and OS than those who had GG genotype (for PFS, HR=0.37, 95% CI=0.17-0.75; for OS, HR=0.36, 95% CI=0.13-0.87). For ERCC2 rs13181 polymorphism, carriers with CC genotype demonstrated significantly increased hazards of progression of disease and death in multivariate model (for PFS, HR=0.48, 95% CI=0.26-0.88; for OS, HR=0.44, 95% CI=0.20-0.91). In conclusion, our finding suggests that ERCC1 rs3212986 and ERCC2 rs13181 gene polymorphism could influence the response to chemotherapy and clinical outcome of gastric cancer.     

Genetic variability of DNA repair mechanisms influences chemotherapy outcome of gastric cancer

Genetic variability of DNA repair mechanisms influences chemotherapy treatment outcome of gastric cancer. We conducted a cohort study to investigate the role of ERCC1-ERCC2 gene polymorphisms in the chemotherapy response and clinic outcome of gastric cancer. Between March 2011 and March 2013, 228 gastric patients who were newly diagnosed with histopathology were enrolled in our study. Genotypes of ERCC1 rs11615, rs3212986, rs2298881 and ERCC2 rs3212986 were conducted by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. We found that individuals carrying TT genotype of ERCC1 rs11615 and CC genotype of ERCC1 rs2298881 were associated with better response to chemotherapy and longer survival time of gastric cancer. Moreover, individuals with AA genotype of ERCC2 rs1799793 were correlated with shorter survival of gastric cancer. In conclusion, ERCC1 rs11615, rs2298881 and ERCC2 rs1799793 polymorphism play an important role in the treatment outcome of gastric cancer.     

Genetic polymorphisms in nucleotide excision repair pathway influences response to chemotherapy and overall survival in osteosarcoma

We analyzed the role of genetic polymorphisms of six important NER pathway genes in response to chemotherapy and clinical outcome of osteosarcoma patients. A prospective study including 172 osteosarcoma patients was conducted between January 2009 and January 2011. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for ERCC1 rs11615 and rs2298881, ERCC2 rs13181 and rs1799793, ERCC4 rs1800067, ERCC5 rs1047768, XPA 1800975, and XPC rs2228000 and rs2228001 gene polymorphisms. By logistic regression analysis, TT genotype of ERCC1 rs11615 genetic polymorphism was significant correlated with poor response to chemotherapy when compared with wide-type genotype (OR=0.27, 95% CI=0.10-0.71). AC and CC genotype of ERCC1 rs2298881 were significantly associated with poor response to chemotherapy when compared with AA genotype (For AC genotype, OR=0.45, 95% CI=0.21-0.97; for CC genotype, OR=0.19, 95% CI=0.06-0.58). By Cox proportional hazards regression analysis, TT genotype of ERCC1 rs11615 and CC genotype of ERCC1 rs2298881 suffered a 3.16 and 3.57-fold increased hazards of death (For ERCC1 rs11615, HR=3.16, 95% CI=1.19-9.16; for ERCC1 rs2298881, HR=3.57, 95% CI=1.10-11.35). In conclusion, our findings suggest that ERCC1 rs11615 and ERCC1 rs2298881 genetic polymorphisms are significantly associated with poor response to chemotherapy and unfavourable survival of osteosarcoma.     

Investigation on the DNA repaired gene polymorphisms and response to chemotherapy and overall survival of osteosarcoma

The aim of the present study was to evaluate the influence of polymorphisms in NER and HRR pathways on the response to cisplatin-based treatment and clinical outcome in osteosarcoma patients. 214 osteosarcoma patients treated with cisplatin-based chemotherapy were collected between January 2008 and January 2011. Genotypes of ERCC1 rs11615, ERCC2 rs1799793 and rs13181, NBN rs709816, RAD51 rs1801320, and XRCC3 rs861539 were conducted by Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) assay. By conditional logistic regression analysis, patients carrying CC genotype of ERCC1 rs11615 showed a significant more good responder than TT genotype, and the OR (95% CI) was 2.51 (1.02-6.85). In the Cox proportional hazards model, after adjusting for potential confounding factors, we found that individuals carrying CC genotype of ERCC1 rs11615 was associated with decreased risk of death from osteosarcoma, and the HR (95% CI) was 0.43 (0.15-0.93). In conclusion, our results suggest that ERCC1 rs11615 polymorphism in the DNA repair pathways play an important role in the response to chemotherapy and overall survival of osteosarcoma.     

Association of single nucleotide polymorphisms of DNA repair genes in NER pathway and susceptibility to pancreatic cancer

In our study, we conducted a case-control study to investigate the association of ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, XPA, XPC and DDB2 gene polymorphisms in the risk of pancreatic cancer. Between May 2012 and May 2014, a total of 246 patients with who were newly diagnosed with histopathologically confirmed primary pancreatic cancer and 246 controls were selected into our study. Genotyping of ERCC1 rs3212986 and rs11615, ERCC2 rs13181, ERCC3 rs4150441, ERCC4 rs6498486, ERCC5 rs873601, XPA rs2808668, XPC rs2228000, XPC rs2228001 and DDB2 rs2029298 were analyzed using polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). By conditional logistic regression analysis, individuals carrying with TT genotype of ERCC1 rs3212986 and GG genotype of ERCC2 rs13181 were associated with increased risk of pancreatic cancer when compared with wide-type genotype, and the adjusted ORs (95% CI) were 2.40 (1.29-4.52) and 2.27 (1.26-4.15), respectively. We found that individuals carrying with GT+TT genotype of ERCC1 rs3212986 and TG+GG genotype of ERCC2 rs1318 gene polymorphisms were correlated with higher risk of pancreatic cancer in smokers when compared with non-smokers, and the adjusted ORs (95% CI) were 1.89 (1.05-3.40) and 1.88 (1.06-3.34), respectively. In conclusion, our study suggests that ERCC1 rs3212986 and ERCC2 rs1318 gene polymorphisms contribute to the development of pancreatic cancer, especially in smokers.     

Nucleotide excision repair gene ERCC1 polymorphisms contribute to cancer susceptibility: a meta-analysis

Individual studies of the associations between excision repair cross-complimentary group 1 (ERCC1) polymorphisms and cancer susceptibility have shown inconclusive results. To derive a more precise estimation of the relationship between three well-characterised polymorphisms on ERCC1 and the risk of cancer, we performed a meta-analysis based on 48 publications. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the associations. We found that ERCC1 17677A (rs3212961) variant genotypes were associated with significantly increased overall risk of cancer without substantial heterogeneity (AA versus CC, OR = 1.36, 95% CIs: 1.10-1.68; AC versus CC: OR = 1.11, 95% CIs: 0.99-1.26; dominant comparison: AA/AC versus CC: OR = 1.15, 95% CIs: 1.02-1.29; recessive comparison: AA versus AC/CC: OR = 1.25, 95% CIs: 1.05-1.49). The ERCC1 19007 C (rs11615) allele had null effects on overall risk of cancer; but in the stratified analyses, we observed an elevated association in Asian populations with homozygote variants and hospital-based controls. In addition, during further stratified analyses of cancer groups, homozygote variants were found that are associated with lung cancer and smoking-related cancers. Also, the observed ERCC1 19007 C heterozygote variant contributes to the development of skin cancer. However, the ERCC1 8092C > A (rs3212986) polymorphism did not appear to have an effect on cancer risk. Additionally, no evidence of publication bias was observed in these polymorphisms. Our meta-analysis supports the conclusion that the ERCC1 17677A > C and ERCC1 19007T > C polymorphisms, but not the ERCC1 8092C > A polymorphism, are low-penetrance risk factors for cancer development.     

Polymorphisms in ERCC1 and XPF gene and response to chemotherapy and overall survival of non-small cell lung cancer

We conducted a perspective study to assess the association between ERCC1 and XPF polymorphisms and response to chemotherapy and clinical outcome of NSCLC receiving chemotherapy. Between May 2009 and May 2011, a prospective study was conducted on 240 NSCLC cases. Genotypes of ERCC1 (rs11615, rs3212986 and rs2298881) and XPF (rs2276465 and rs6498486) were performed by Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP) assay. By conditional logistic regression analysis, patients carrying AA genotype of ERCC1 rs11615 showed more CR+PR to chemotherapy when compared with GG genotype, and the adjusted OR (95% CI) was 2.73 (1.21-6.18). By Cox regression analysis, AA genotype of ERCC1 rs11615 was associated with longer overall survival of NSCLC, and the adjusted HR (95% CI) was 0.38 (0.14-0.96). In conclusion, our study found that ERCC1 rs11615 polymorphism can influence the chemotherapy response and overall survival of NSCLC patients receiving cisplatin-based chemotherapy.     

Association of NER pathway gene polymorphisms with susceptibility to laryngeal cancer in a Chinese population

We systematically analyzed the association of nine SNPs of seven key NER pathway genes with the development of laryngeal cancer patients, and investigated whether NER pathway polymorphisms could serve as potential biomarkers for laryngeal cancer risk. 271 patients with pathologically proven laryngeal cancer and 271 control subjects were included in our study. Genotyping of ERCC1 rs11615 and rs2298881, ERCC2 rs13181 and rs50871, ERCC3 rs4150441, ERCC4 rs6498486, ERCC5 rs2094258, XPA rs2808668 and XPC rs2228001 were analyzed by polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). By conditional logistic regression analysis, individuals carrying the TT genotype of ERCC1 rs11615 were correlated with an increased risk of larynx cancer when compared with the CC genotype (OR=1.89, 95% CI=1.07-3.37; P value=0.02). Moreover, individuals with the GG genotype of ERCC2 rs50871 were associated with an elevated risk of larynx cancer when compare with the TT genotype (OR=2.03, 95% CI=1.15-3.63; P value=0.01). We found a significant interaction between ERCC2 rs50871 polymorphism and tobacco smoking in the risk of larynx cancer (P for interaction <0.05). In conclusion, our study showed that ERCC1 rs11615 and ERCC2 rs50871 polymorphisms could influence the risk of larynx cancer in Chinese population, particularly among smokers.     

Genetic variability of ERCC1 genes in NER pathway influences the treatment outcome of gastric cancer

We conducted a prospective study to analyze whether six SNPs in ERCC1 gene could serve as potential biomarkers for prognosis of gastric cancer. Between January 2010 and December 2012, 270 patients with pathologically proven gastric cancer and receiving platinum-based chemotherapy were recruited in our study. Genotyping of the ERCC1 rs11615, rs2298881, rs3212955, rs3212961, rs3212986 and rs735482 were carried out using the Sequenom MassARRAY platform. By logistic regression analysis, patients carrying the GT and TT genotypes of rs3212986 showed a significantly poorer response to chemotherapy than did those carrying the GG genotype, and the ORs (95% CI) were 0.47 (0.25-0.88) and 0.18 (0.08-0.41), respectively. By Cox proportional hazards models, the GT and TT genotypes of rs3212986 were correlated with increased risk of death when compared with the GG genotype, and the adjusted HRs (95% CIs) were 1.79 (1.01-3.16) and 2.57 (1.18-5.62), respectively. However, we did not find significant association between ERCC1 rs11615, rs2298881, rs3212955, rs3212961 and rs735482 and response to chemotherapy and overall survival in patients with gastric cancer. In conclusion, the results of the present retrospective study indicate that there is a significant difference in biological behavior between ERCC1 rs3212986 gene polymorphism and treatment outcome of gastric cancer.     

Effect of TOP2A and ERCC1 gene polymorphisms on the efficacy and toxicity of cisplatin and etoposide-based chemotherapy in small cell lung cancer patients

IntroductionThe main treatment regimen for small cell lung cancer (SCLC) involves platinum-based chemotherapy (cisplatin or carboplatin) and etoposide. Single nucleotide polymorphisms (SNPs) in TOP2A and ERCC1 genes were tested as prognostic and predictive factors in non-small cell lung cancer (NSCLC). There are limited data about the clinical relevance of these genetic alterations in SCLC. We undertook this retrospective study to determine the influence of SNPs in TOP2A (rs34300454; rs13695; rs11540720) and ERCC1 (rs11615; rs3212986) genes on the efficiency and toxicity of chemotherapy with platinum and etoposide in SCLC Caucasian patients.Material and methodsThe studied group included 103 Caucasian SCLC patients (65 male, 38 female, median age 65 ±7.5 years). Detailed clinical-demographical data were collected and response to treatment was monitored. DNA was isolated from peripheral blood leukocytes using QIAamp DNA Mini Kit. Single nucleotide polymorphisms were analyzed using TaqMan hydrolyzing probes in real-time PCR technique on an Eco Illumina device.ResultsPatients with C/C genotype in rs13695 of the TOP2A gene had significantly lower risk of neutropenia during chemotherapy than C/T heterozygous patients (p = 0.02, χ² = 5.51, OR = 2.676, 95% CI: 1.165–6.143). Patients harbouring homozygous C/C genotype in rs3212986 of the ERCC1 gene had significantly higher risk of anaemia during chemotherapy, than heterozygous C/A patients (p = 0.045, χ² = 4.01, OR = 0.417, 95% CI: 0.175–0.991). Furthermore, heterozygous G/A genotype in rs11615 of the ERCC1 gene was associated with significant shortening of OS (9 vs. 12 months) compared to homozygous A/A genotype (p = 0.01, χ² = 6.31, HR = 1.657, 95% CI: 1.0710–2.5633).ConclusionsSNPs in ERCC1 and TOP2 genes may be associated with the toxicities and survival of SCLC patients treated with cisplatin and etoposide.     

Role of common ERCC1 polymorphisms in cisplatin‐resistant epithelial ovarian cancer patients: A study in Chinese cohort

Epithelial ovarian cancer (EOC) contributes the majority of death cases among various ovarian malignancies. Although a standard method of treatment is the surgical removal of malignant tissue followed by platinum‐based chemotherapy, a group of patients does not respond appropriately to cisplatin. An appropriate response to cisplatin has been linked with the nucleotide excision repair mechanism. The present study aims to investigate the role of polymorphisms in DNA repair genes, excision repair cross‐complementation group 1 (ERCC1) with susceptibility to EOC development and tumour response to platinum‐based chemotherapy in Chinese EOC patients. Patients (n = 559) reporting to the Department of Oncology and general surgery, the First Affiliated Hospital of Kunming Medical University, were enrolled in the study. Three hundred twenty‐three healthy controls hailing from similar geographical areas without a history of cancer enrolled as healthy controls. Excision repair cross‐complementation group 1 polymorphisms (rs11615, rs3212986, rs735482, rs2336219, rs3212980, rs3212964, rs3212961 and rs2298881) were genotyped by appropriate methods. Distribution of genotypes and allele for ERCC1 polymorphisms (rs11615, rs3212986, rs735482, rs2336219, rs3212980, rs3212964, rs3212961 and rs2298881) were comparable among healthy controls and EOC patients. Interestingly, homozygous mutant and the minor allele for rs11615 and rs3212986 polymorphisms were significantly higher in nonresponder EOC patients when compared to those with a proper response to cisplatin treatment. The prevalence of other SNPs was comparable among the two treated clinical categories. Furthermore, combined genotype revealed significant association of rs11615: TT/ rs3212986: AA genotype combination with cisplatin nonresponder. Variants of rs11615, rs3212986 polymorphisms are associated with cisplatin resistance in Chinese EOC patients. Combined rs11615 and rs3212986 genotypes can be used as a predictive biomarker for platinum‐based chemotherapy outcomes.     

Analysis of ERCC2/XPD functional polymorphisms in systemic lupus erythematosus

Sunlight/ultraviolet (UV) irradiation has been recognized as an important risk factor for developing systemic lupus erythematosus (SLE). However, the interpretation of genetic variations involved in UV‐light sensitivity is largely unknown. Recent studies indicated that two genetic variations of ERCC2/XPD gene (rs1799793 in exon 10 and rs13181 in exon 23) have been found to exert negative influences on nucleotide excision repair system. To analyse the possible contribution of the ERCC2/XPD functional single nucleotide polymorphisms in genetic susceptibility to SLE, the rs13181 and rs1799793 SNPs in ERCC2/XPD were genotyped by polymerase chain reaction followed by restriction fragment length polymorphism analysis. Association was studied by case–control analyses using samples from 172 SLE patients and 160 healthy controls. Haplotype analysis was performed to detect the association with genetic predisposition to SLE and the clinical features. Although these two functional genetic variations are linked to several immune dysfunction‐induced diseases, no statistically significant differences in allele or genotype frequencies were observed between SLE patients and controls. Haplotype analysis showed that none of ERCC2/XPD haplotypes was associated with the incidence of SLE disease, nor the preference of clinical features. In conclusion, the ERCC2/XPD functional polymorphisms analysed in this study showed no association in genetic susceptibility to SLE.     

No association of ERCC1 C8092A and T19007C polymorphisms to cancer risk: a meta-analysis

ERCC1 (excision repair cross complementation group 1) is a subunit of the nucleotide excision repair complex, which can perform DNA strand incision correction of DNA damage. Association studies on the ERCC1 polymorphisms (C8092A and T19007C) in cancer had shown conflicting results. We performed a meta-analysis from all eligible case-control studies to assess the purported associations. Overall, the 19007C allele (3 853 patients and 4 349 controls) showed no significant effect on cancer risk compared to 19007T allele (P=0.39, odds ratio (OR)=0.95; 95% confidence interval (CI) 0.85-1.06, P(heterogeneity)=0.001) in all subjects. Meta-analysis under other genetic contrasts did not reveal any significant association of T19007C to cancer in all subjects, Caucasians and Asians. The 19007C allele (2 279 patients and 2 808 controls) showed no significant effect on lung cancer risk compared to 19007T allele (P=0.72, OR=0.94, 95% CI 0.69-1.29, P(heterogeneity)=0.0001) in all subjects. No significant effect of 8092A allele (3 865 patients and 3 750 controls) on cancer risk in all subjects (P=0.85, OR=1.01, 95% CI 0.94-1.08, P(heterogeneity)=0.92) and in Caucasians and Asians compare to 8092C. No evidences of association of C8092A (501 patients and 620 controls) to squamous cell carcinoma were found. The accumulated evidence indicated ERCC1 T19007C and C8092A might not be risk factors for cancer. Significant between-study heterogeneity existed in T19007C, which arose from a study showing significant protecting effect of 19007C allele compare to 19007T allele in smokers. More studies based on larger, stratified case-control population should be required to further evaluate the role of ERCC1 C8092A and T19007C polymorphisms in different cancer, especially in smokers.     

Interleukin-17A gene polymorphism is associated with susceptibility to gastric cancer

We conducted a study to investigate the role of three common SNPs in the IL-17A and IL-17F genes (rs2275913G>A, rs3748067C>T and rs763780T>C) in the development of gastric cancer, and their interaction with H.pylori infection. A total of 326 patients with gastric cancer and 326 control subjects were consecutively recruited between May 2012 and May 2014. Genotyping of IL-17A rs2275913G>A and rs3748067C>T and IL-17F rs763780T>C was performed in a 384-well plate format on the Sequenom MassARRAY platform. By logistic regression analysis, individuals carrying the GA and AA genotypes of IL-17 rs2275913G>A were significantly associated with an increased risk of gastric cancer when compared with GG genotype, and the adjusted Ors (95% CI) were 1.46 (1.03-2.06) for GA genotype and 2.57 (1.51-4.43) for AA genotype. We observed that the GA+AA genotype of rs2275913 was associated with an increased risk of gastric cancer among H.pylori infection subjects (OR=2.21, 95% CI=1.29-3.79). In conclusion, we found that there was a significant association between L-17A rs2275913G>A polymorphism and increased gastric cancer risk, especially in H.pylori infection subjects.     

Lack of association between DNA repair gene ERCC1 polymorphism and risk of lung cancer in a Chinese population

The ERCC1 (Excision Repair Cross Complementation Group 1) gene is involved in the nucleotide excision repair pathway. This study was designed to examine whether ERCC1 Asn118Asn (G19007A) polymorphism, which has been associated with risk of some cancers among Caucasians, may be associated with risk of lung cancer in a Chinese population. ERCC1 Asn118Asn (G19007A) genotypes were determined in DNA samples from 151 cases and 143 controls. The distribution of genotypes between cases and controls was not associated with an increased risk of lung cancer (AA versus GG: adjusted OR (odds ratio) = 1.41, 95% CI (confidence interval) = 0.76-2.59; AG versus GG: adjusted OR = 0.78, 95% CI = 0.47-1.29; and AA + AG versus GG: adjusted OR = 0.93, 95% CI = 0.73-1.19). The frequency A (0.20) of the A-allele was significantly lower among these Chinese controls than in the Caucasian control populations (A = 0.54-0.65) (All P < 0.001). No statistically significant effects of age, histological subtype or smoking were found. These findings suggest that ERCC1 Asn118Asn (G19007A) polymorphism may play a limited role for lung cancer in this Chinese population.     

Lack of correlation between ERCC1 (C8092A) single nucleotide polymorphism and efficacy/toxicity of platinum based chemotherapy in Chinese patients with advanced non-small cell lung cancer

PurposeWe investigated whether single nucleotide polymorphism of excision repair cross-complementation group 1 C8092A affected the clinical outcomes and toxicity in advanced stage non-small cell lung cancer patients receiving first line platinum based chemotherapy.Material/MethodsA total of 300 chemotherapy treated patients were examined for C8092A genotypes in peripheral blood samples.ResultsOverall response rate was 33.6% and median overall survival was 13.5 months. There was no significant correlation between C8092A single nucleotide polymorphism and overall survival, tumor response or toxicity for platinum-based chemotherapy.ConclusionsExcision repair cross-complementing group 1 (ERCC1) showed controversial results in different studies that have been carried out until now. In our Chinese population there is no correlation between ERCC1 C8092A SNP and efficacy or toxicity. Ethnicity could be a possible explanation for these controversial results.     

DNA repair gene ERCC2 polymorphisms and risk of squamous cell carcinoma of the head and neck

Introduction

Genetic aberrations of DNA repair enzymes are known to be common events and to be associated with different cancer entities. Aim of the following study was to analyze the genetic association of single nucleotide polymorphisms (SNP) of the DNA repair genes with the risk of squamous cell carcinoma of the head and neck (HNSCC).

Materials and methods

Genetic variants ERCC2 Lys751Gln (rs13181), ERCC2 Asp312Asn (rs1799793), XRCC1 Arg194Trp (rs1799782); XRCC1 Gln399Arg (rs25487), XRCC1 Arg280His (rs25489) and XRCC3 Thr241Met (rs861539) were analyzed in a primary study group comprising 169 patients with histologically confirmed HNSCC and 463 healthy control subjects. Polymorphisms associated with HNSCC were furthermore analyzed in an independent replication study including 125 HNSCC.

Results

Only the ERCC2 751 Gln/Gln genotype was associated with HNSCC in the primary study (p = 0.033) and in the replication study (p = 0.023), resulting in an overall odds ratio of 0.54 (95% confidence interval 0.35–0.92; p = 0.006).

Conclusion

Carriers of the homozygous ERCC2 751 Gln/Gln genotype may be at lower risk for HNSCC.     

Predictive role of miR-146a rs2910164 (C>G), miR-149 rs2292832 (T>C), miR-196a2 rs11614913 (T>C) and miR-499 rs3746444 (T>C) in the development of hepatocellular carcinoma

We conducted a case-control study to evaluate the association of miR-146a rs2910164 (C>G), miR-149 rs2292832 (T>C), miR-196a2 rs11614913 (T>C) and miR-499 rs3746444 (T>C) polymorphisms with the risk of hepatocellular carcinoma. A total of 274 patients with HCC were collected between January 2013 and December 2014. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was taken to determine the polymorphism of miR-146a C>G, miR-149 T>C, miR-196a2 T>C and miR-499 T>C. By comparing with control groups, patients with HCC were more likely to be males (OR=2.01, 95% CI=1.38-2.95), have older age (OR=1.52, 95% CI=1.09-2.13), have a history of alcohol drinking (OR=2.09, 95% CI=1.49-2.93), and be infected with HBV (OR=32.98, 95% CI=19.70-55.46) and HCV (OR=56.26, 95% CI=23.28-152.98) infection. By conditional regression analysis, individuals carrying the TC and CC genotypes of miR-196a2 T>C were found to be associated with an elevated risk of HCC compared to the TT genotype, and the adjusted odds ratio were 1.50 (1.03-2.17) and 2.86 (1.60-5.16), respectively. Moreover, the TC+CC genotype was correlated with an increased risk of HCC (OR=1.69, 95% CI=1.19-2.41) compared to the wide-type genotype. In conclusion, our results suggested that miR-196a2 T>C polymorphism is associated with HCC risk in Chinese population.     

Association Between PTPN22 Polymorphisms and IgE Responses to Staphylococcal Superantigens in Chronic Urticaria

Protein tyrosine phosphatase-22 (PTPN22) gene encodes lymphoid-specific tyrosine phosphatase (Lyp), an inhibitor of T cell activation. A polymorphism of the PTPN22 gene has been found to be associated with chronic urticaria (CU). We investigated the associations between PTPN22 gene polymorphisms and CU characteristics, including serum specific IgE antibodies response to toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin A (SEA). CU patients (n=409) and normal healthy controls (n=388) were enrolled in the present study. Serum specific IgE to TSST-1 and SEA were measured by ImmunoCAP®. Five PTPN22 single nucleotide polymorphisms, -1123G>C, 1858C>T, 13145A>G, 14943C>T, and 20628A>G, were genotyped. There were no significant differences in genotype or haplotype frequencies of these polymorphisms between the 2 groups. CU patients carrying the GG genotype at 20628A>G (P=0.035) or haplotype 3 [GGG] (P=0.047) had a significantly higher prevalence of serum specific IgE to TSST-1 compared to non-carriers. Similarly, CT/TT genotype at 14943C>T had a significantly higher prevalence of serum specific IgE to SEA (P=0.045). The findings suggest that the PTPN22 gene polymorphisms at 20628A>G and 14943C>T may enhance serum specific IgE responses to TSST-1 and SEA, which may contribute to CU pathogenesis.     

MSH3 rs26279 polymorphism increases cancer risk: a meta-analysis

Previous studies have investigated the association of mutS homolog 3 (MSH3) rs26279 G > A polymorphism with the risk of different types of cancers including colorectal cancer, breast cancer, prostate cancer, bladder cancer, thyroid cancer, ovarian cancer and oesophageal cancer. However, its association with cancer remains conflicting. We performed a comprehensive meta-analysis to derive a more precise estimation of the relationship between MSH3 rs26279 G > A polymorphism and cancer susceptibility. Systematically searching the PubMed and EMBASE databases yielded 11 publications with 12 studies of 3282 cases and 6476 controls. The strength of the association was determined by crude odds ratios (OR) and 95% confidence intervals (CI). Overall, pooled risk estimates demonstrated that MSH3 rs26279 G > A was significantly associated with an increased overall cancer risk under all the genetic models (GG vs. AA: OR = 1.27, 95% CI = 1.09-1.48, P = 0.002; AG vs. AA: OR = 1.10, 95% CI = 1.00-1.21, P = 0.045; GG vs. AG + AA: OR = 1.23, 95% CI = 1.06-1.42, P = 0.005; AG + GG vs. AA: OR = 1.13, 95% CI = 1.04-1.24, P = 0.006; G vs. A: OR = 1.13, 95% CI = 1.05-1.20, P = 0.001). The association was more evident for colorectal cancer and breast cancer. Moreover, the significant association was also observed in the following subgroups: Europeans, Asians, population-based studies, hospital-based studies, and studies comprising relatively large sample size (≥ 200). Our meta-analysis results demonstrated that MSH3 rs26279 G > A polymorphism is associated with an increased risk of overall cancer, especially for the colorectal cancer and breast cancer.