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.     

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.     

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.     

Association of ERCC gene polymorphism with osteosarcoma risk

BackgroundThe relationship between ERCC gene polymorphism and osteosarcoma risk / overall survival of osteosarcoma is still conflicting, and this meta-analysis was performed to assess these associations.Material and methodsThe association studies were identified from PubMed, and eligible reports were included and calculated using meta-analysis method.ResultsFour studies were included for the association of ERCC gene polymorphism with osteosarcoma risk, and nine studies were recruited into this meta-analysis for the relationship between ERCC gene polymorphism and overall survival of osteosarcoma. The meta-analysis indicated that ERCC1 rs3212986 (8092 C>A) gene polymorphism, ERCC1 rs11615 (19007 T>C) gene polymorphism, ERCC2 rs1799793 (A>G) gene polymorphism, ERCC2 rs13181 (Lys751Gln) gene polymorphism were not associated with osteosarcoma risk. ERCC1 rs2298881 (C>A) gene polymorphism, ERCC1 rs3212986 (8092 C>A) gene polymorphism, ERCC1 rs11615 (19007 T>C) gene polymorphism, ERCC2 rs1799793 (Asp312Asn) gene polymorphism were not associated with overall survival of osteosarcoma. Interestingly, ERCC2 rs13181 A allele and GG genotype were associated with overall survival of osteosarcoma, but AA genotype not (A allele: OR = 0.78, 95% CI: 0.65–0.93, P = 0.007; GG genotype: OR = 1.32, 95% CI: 1.05–1.65, P = 0.02; AA genotype: OR = 0.69, 95% CI: 0.45–1.04, P = 0.08).ConclusionERCC2 rs13181 A allele and GG genotype were associated with overall survival of osteosarcoma.     

A 3′ untranslated region polymorphism rs2304277 in the DNA repair pathway gene OGG1 is a novel risk modulator for urothelial bladder carcinoma

Altered DNA repair capacity may affect an individual's susceptibility to cancers due to compromised genomic integrity. This study was designed to elucidate the association of selected polymorphisms in DNA repair genes with urothelial bladder carcinoma (UBC). OGG1 rs1052133 and rs2304277, XRCC1 rs1799782 and rs25487, XRCC3 rs861539, XPC rs2228001, and XPD rs13181 were genotyped using polymerase chain reaction–restriction fragment length polymorphism (PCR‐RFLP) in 200 UBC cases and 200 controls. We found association of OGG1 rs2304277 [odds ratio (OR)_GG = 3.55, 95% confidence interval (CI) = 1.79–7.06] and XPC rs2228001 (OR_AC = 2.38, 95% CI = 1.43–3.94) with UBC. In stratified analysis with respect to smoking status, OGG1 rs2304277 and XPC rs2228001 exhibited increased risk in smokers [(rs2304277 OR_GG = 4.96, 95% CI = 1.51–16.30) (rs2228001 OR_AC = 2.19, 95% CI = 1.02–4.72)] as well as nonsmokers [(rs2304277 OR_GG = 2.95, 95% CI = 1.26–6.90) (rs2228001 OR_AC = 2.57, 95% CI = 1.31–5.04)]. These polymorphisms were also associated with both low‐grade [(rs2304277 OR_GG = 3.73, 95% CI = 1.72–8.09) (rs2228001 OR_AC = 2.18, 95% CI = 1.21–3.92)] and high‐grade tumors [(rs2304277 OR_GG = 3.45, 95% CI = 1.52–7.80) (rs2228001 OR_AC = 2.81, 95% CI = 1.48–5.33)] as well as with non–muscle‐invasive bladder cancer [(rs2304277 OR_GG = 4.03, 95% CI = 1.87–8.67) (rs2228001 OR_AC = 2.14, 95% CI = 1.20–3.81)] and muscle‐invasive bladder cancer [(rs2304277 OR_GG = 3.06, 95%CI = 1.31–7.13) (rs2228001 OR_AC = 2.95, 95%CI = 1.51–5.75)]. This is the first study on DNA repair gene polymorphisms and UBC in the Pakistani population. It identifies OGG1 rs2304277 and replicates XPC rs2228001 as significant modulators of UBC susceptibility.     

Genetic polymorphisms in the nucleotide excision repair pathway and lung cancer risk: a meta-analysis

Various DNA alterations can be caused by exposure to environmental and endogenous carcinogens. Most of these alterations, if not repaired, can result in genetic instability, mutagenesis and cell death. DNA repair mechanisms are important for maintaining DNA integrity and preventing carcinogenesis. Recent lung cancer studies have focused on identifying the effects of single nucleotide polymorphisms (SNPs) in candidate genes, among which DNA repair genes are increasingly being studied. Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. We identified a sufficient number of epidemiologic studies on lung cancer to conduct a meta-analysis for genetic polymorphisms in nucleotide excision repair pathway genes, focusing on xeroderma pigmentosum group A (XPA), excision repair cross complementing group 1 (ERCC1), ERCC2/XPD, ERCC4/XPF and ERCC5/XPG. We found an increased risk of lung cancer among subjects carrying the ERCC2 751Gln/Gln genotype (odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.14 - 1.49). We found a protective effect of the XPA 23G/G genotype (OR = 0.75, 95% CI = 0.59 - 0.95). Considering the data available, it can be conjectured that if there is any risk association between a single SNP and lung cancer, the risk fluctuation will probably be minimal. Advances in the identification of new polymorphisms and in high-throughput genotyping techniques will facilitate the analysis of multiple genes in multiple DNA repair pathways. Therefore, it is likely that the defining feature of future epidemiologic studies will be the simultaneous analysis of large samples.     

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.     

Polymorphisms of the XRCC3 C722T and the RAD51 G135C genes and the risk of head and neck cancer in a Polish population

Genetic variations in DNA repair genes may affect an individual's susceptibility to head and neck cancer. We performed a case–control study to test the association between head and neck cancer risk and two polymorphisms: the C722 T of the XRCC3 and the G135C of the RAD51 —genes of DNA double strand break (DSB) repair by homologous recombination (HRR). Genotypes were determined by PCR-restriction fragment lenght polymorphism (PCR-RFLP). DNA was isolated from peripheral blood lymphocytes of a group of 288 patients consisting of 97 subjects with precancerous hyperplastic laryngeal lesions (PHLL) and 191 subjects with head and neck squamous cell carcinoma (HNSCC) as well as 353 healthy control donors. We found an association between PHLL and the 722CT (OR 6.67; 95% CI 3.02–14.74) as well as 722 TT (OR 4.65; 95% CI 2.30–9.43) variants of the XRCC3 gene. Similar relation was observed between these genotypes and HNSCC (OR 2.59; 95% CI 1.61–4.16 and OR 5.54; 95% CI 3.22–9.52, respectively). Moreover, we also observed an association between PHLL (OR 6.04; 95% CI 3.69–9.90) and HNSCC (OR 6.04; 95% CI 3.69–9.90) and the135GC variant of the RAD51 gene. The gene–gene interaction between XRCC3 and RAD51 polymorphic variants may contribute to higher prevalence of PHLL. The increased risk of this disease was observed in case of the combination of the 722CT/135GC (OR 3.81; 95% CI 1.55–9.75) as well as the 722 TT/135GC genotypes (OR 5.33; 95% CI 1.96–14.47). The presence of the same genes combinations plays a part in higher probability of HNSCC occurrence (OR 2.42; 95% CI 1.22–4.79 for 722CT/135GC and OR 3.63; 95% CI 1.69–7.76 for 722 TT/135GC). We also found an association between these XRCC3 or RAD51 polymorphic variants and smoking status in PHLL (ORs 2.85–10.28 and 1.82–7.35, respectively) and HNSCC patients (ORs 2.94–13.93 and 1.36–3.94, respectively) as well as alcohol intake among PHLL (ORs 3.44–6.12 and 3.52–8.43, respectively) and HNSCC subjects (ORs 2.71–7.01 and 2.33–4.62, respectively). In conclusion our data showed that the C722 T and the G135C polymorphisms of the XRCC3 and the RAD51 genes might be associated with HNSCC. Finally we suggested that these polymorphisms might be used as predictive factor of precancerous lesion for head and neck cancer in a Polish population.     

The effect of UGT1A and UGT2B polymorphisms on colorectal cancer risk: Haplotype associations and gene–environment interactions

UDP‐glucuronosyltransferases (UGTs) play an important role in the phase II metabolism of exogenous and endogenous compounds. As colorectal cancer (CRC) etiology is thought to involve the biotransformation of dietary factors, UGT polymorphisms may affect CRC risk by altering levels of exposure. Genotyping of over 1800 Caucasian subjects was completed to identify the role of genetic variation in nine UGT1A and five UGT2B genes on CRC risk. Unconditional logistic regression and haplotype analyses were conducted to identify associations with CRC risk and potential gene‐environment interactions. UGT1A haplotype analysis found that the T‐G haplotype in UGT1A10 exon 1 (block 2: rs17864678, rs10929251) decreased cancer risk for the colon [proximal (OR = 0.28, 95% CI = 0.11–0.69) and for the distal colon (OR = 0.32, 95% CI = 0.12–0.91)], and that the C‐T‐G haplotype in the 3′ region flanking the UGT1A shared exons (block 11: rs7578153, rs10203853, rs6728940) increased CRC risk in males (OR = 2.56, 95% CI = 1.10–5.95). A haplotype in UGT2B15 containing a functional variant (rs4148269, K523T) and an intronic SNP (rs6837575) was found to affect rectal cancer risk overall (OR = 2.57, 95% CI = 1.21–5.04) and in females (OR = 3.08, 95% CI = 1.08–8.74). An interaction was found between high NSAID use and the A‐G‐T haplotype (block 10: rs6717546, rs1500482, rs7586006) in the UGT1A shared exons that decreased CRC risk. This suggests that UGT genetic variation alters CRC risk differently by anatomical sub‐site and gender and that polymorphisms in the UGT1A shared exons may have a regulatory effect on gene expression that allows for the protective effect of NSAIDs on CRC risk. © 2014 Wiley Periodicals, Inc.     

Toll-like receptor 1 gene polymorphisms in childhood IgA nephropathy: a case-control study in the Korean population

Toll‐like receptors (TLRs) are innate immune mediators that stimulate nuclear factor kappa B and the inflammatory cytokines. TLR1 is expressed in renal tubular epithelial cells when the kidney is injured, but the role of TLR1 gene in glomerulonephritis has not been clearly elucidated. We aimed to investigate the association of TLR1 polymorphisms with immunoglobulin A nephropathy (IgAN) in children. One hundred and ninety pediatric patients with biopsy‐proven IgAN and 283 healthy control subjects were enrolled. Two single nucleotide polymorphisms of TLR1 gene [rs4833095 (missense, Asn248Ser) and rs5743557 (promoter, ?414C/T)] were selected and genotyped by direct sequencing. For rs4833095, the C/T genotype in the codominant model (vs. the T/T genotype) [odds ratio (OR) = 2.11, 95% confidence interval (CI): 1.21–3.69, P = 0.009] and the genotype containing C allele (C/T and C/C) in the dominant model (vs. the T/T genotype) (OR = 1.97, 95% CI: 1.16–3.34, P = 0.012) were associated with an increased risk of IgAN. For rs5743557, the T/T genotype in the codominant model (vs. the C/C genotype) (OR = 1.74, 95% CI: 1.02–2.96, P = 0.041) appeared to be associated with IgAN risk. In haplotype analysis, the CT haplotype revealed an association with IgAN (codominant model, OR = 1.38, 95% CI: 1.06–1.80, P = 0.017; dominant model, OR = 1.76, 95% CI: 1.16–2.67, P = 0.008). After Bonferroni correction, the association of the genotypes of rs4833095 and the CT haplotype with IgAN risk remained significant. These findings suggest that TLR1 gene polymorphisms may affect IgAN susceptibility in Korean children.     

Polymorphism in the nuclear excision repair gene ERCC2/XPD: association between an exon 6-exon 10 haplotype and susceptibility to cutaneous basal cell carcinoma

Cutaneous basal cell carcinoma (BCC) risk is mediated by interactions between ultraviolet radiation (UVR) and host factors, including DNA repair efficiency. We investigated the association between BCC risk and SNPs in exon 6 (c.466C > A, dbSNP238406:g.C > A; designated C/A156), exon 10 (c.932G > A, dbSNP1799793:g.G > A; designated G/A312), and exon 23 (c.2251A > C, dbSNP13181:g.A > C; designated A/C751) of the nucleotide excision repair gene, XPD (ERCC2; excision repair cross-complementing repair deficiency, complementation 2 [xeroderma pigmentosum D]). XPD genotype frequencies were not significantly different in 509 cases and 379 controls, although AA156 (odds ratio [OR]=0.61, 95% confidence interval [CI]=0.37-1.01, P=0.052) and AA312 (OR=0.65, 95% CI=0.40-1.05, P=0.08) were linked with reduced risk. A156-A312 and A156-A312-A751 haplotype frequencies however, were significantly lower in cases than controls (OR=0.12, 95% CI=0.05-0.31, P < 0.001; OR=0.10, 95% CI=0.03-0.33, P < 0.001). We confirmed the robustness of these findings by showing significant associations of the haplotypes with risk in two randomly selected equal sized groups of cases and controls and, using the false positive report probability (FPRP) approach (FPRP values < 0.001 and < 0.004, respectively). A156-A312 was similarly associated with reduced risk in subgroups, including cases with no family history of skin cancer, with only BCC on the head/neck, and those with a high rate of increase in BCC numbers. The association was not dependent on gender, age, or extent of UVR exposure. A156-A312 was found in 6.3% of controls and the corresponding risk haplotype, C156-G312 (OR=1.65, 95% CI=1.21-2.26, P=0.002) in 35.4% of controls. We interpret these data as showing that XPD SNP mediate susceptibility to BCC.     

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.     

A meta-analysis of DNA repair gene <Emphasis Type="Italic">XPC</Emphasis> polymorphisms and cancer risk

Polymorphisms (A33512C, C21151T and PAT −/+) of the xeroderma pigmentosum group C (XPC) were shown to contribute to genetic susceptibility to cancer. However, association studies on these polymorphisms in cancer have shown conflicting results. Thus, we performed a meta-analysis. Overall, there was no significant association between 33512C (9,091 patients and 11,553 controls) and cancer risk. No significant association was found in stratification analysis by tumor sites and ethnicities except an elevated lung cancer risk under the recessive genetic model in all subjects [P = 0.04, odds ratio (OR) = 1.20, 95% confidence interval (CI) 1.00–1.45, P _{heterogeneity} = 0.88]. There was no significant association between 21151T (5,227 patients and 5,959 controls) and cancer risk in all subjects but an increased cancer risk in Caucasians under the recessive genetic model (P = 0.006, OR = 1.45, 95% CI 1.11–1.90, P _{heterogeneity} = 0.75) and homozygote comparison (P = 0.02, OR = 1.41, 95% CI 1.07–1.81, P _{heterogeneity} = 0.41). It might be that 21151T increases bladder cancer risk under the recessive genetic model (P = 0.02, OR = 1.49, 95% CI 1.06–2.09, P _{heterogeneity} = 0.47) and homozygote comparison (P = 0.02, OR = 1.49, 95% CI 1.05–2.11, P _{heterogeneity} = 0.23). There was no significant association between PAT + (4,600 patients and 4,866 controls) and cancer risk in all subjects. An increased cancer risk in Caucasians was found under the recessive genetic model (P = 0.02, OR = 1.20, 95% CI 1.03–1.40, P _{heterogeneity} = 0.37) and homozygote comparison (P = 0.008, OR = 1.26, 95% CI 1.06–1.50, P _{heterogeneity} = 0.13). The XPC PAT + allele might increase head and neck cancer risk (P = 0.02, OR = 1.29, 95% CI 1.04–1.59, P _{heterogeneity} = 0.15). More studies based on larger, stratified, case–control population, especially studies investigate the combined effect of XPC A33512C, C21151T, and PAT, are required to further evaluate the role of these polymorphisms in different cancers.     

ERCC1 intron 1 was associated with breast cancer risk

Introduction

There are numerous studies addressing associations of polymorphisms in DNA repair genes and cancer risks because accurate and efficient DNA repair is crucial to genomic integrity and fidelity. ERCC1 is important in DNA nucleotide excision repair.

Material and methods

We genotyped constitutive variants of ERCC1 in approximately 300 adults with breast adenocarcinoma and 126 controls of Iranian women. In total, 426 Iranian sporadic breast cancer affected women compared to the control group were studied by PCR-RFLP for ERCC1 variant.

Results

The genotype ERCC1 TT has the highest frequency in both groups (36.6 in patients and 8.5 in controls). The genotype ERCC1 was the most important risk factor in our population [GG/AA odds ratio: 0.692, 95% confidence interval (CI): 0.4-1.199, p = 0.188; GG/AG odds ratio: 3.333, 95% CI: 1.917-5.795, p = 0.001; AA/AG odds ratio: 0.208, 95% CI: 0.124-0.348, p = 0.342].

Conclusions

Our patients was associated with breast cancer risk.     

The association between BANK1 and TNFAIP3 gene polymorphisms and systemic lupus erythematosus: a meta-analysis

The past decade has witnessed hundreds of reports declaring or not being able to replicable genetic association with systemic lupus erythematosus (SLE) susceptibility. BANK1 is a gene that encodes a B‐cell‐specific scaffold protein and its activation can affect B‐cell‐receptor‐induced calcium mobilization from intracellular calcium stores. TNFAIP3 encodes the ubiquitin‐modifying enzyme, also known as A20, which is a cytoplasmic zinc finger protein that inhibits nuclear factor kappa‐B (NFKB) activity and tumour necrosis factor (TNF)‐mediated programmed cell death. The association of BANK1 and TNFAIP3 polymorphism with SLE has been reported in several studies. The aim of this study was to assess whether combined evidence shows the association between BANK1 and TNFAIP3 polymorphism and SLE. We report the results of a meta‐analysis of genome‐wide association scans and replication in independent sets for BANK1 and TNFAIP3 polymorphism and SLE that includes 12 416 subjects with SLE and 19 113 control subjects. Meta‐odds ratios (ORs) and 95% confidence intervals (CIs) based on random effects models. Both of BANK1 and TNFAIP3 harbour several controversial single nucleotide polymorphisms (SNPs). We selected and identified three SNPs of BANK1 associated with SLE (rs17266594, P = 1.949e‐10; OR = 1.380; 95% CI: 1.250–1.525; rs10516487, P = 2.642e‐13; OR = 1.317; 95% CI: 1.223–1.417; rs3733197, P = 3.452e‐06; OR = 1.193; 95% CI: 1.107–1.286); one SNP of TNFAIP3 associated with SLE (rs2230926, P = 1.502e‐12; OR = 1.826; 95% CI: 1.545–2.157). This meta‐analysis demonstrates a significant association between BANK1 and TNFAIP3 gene polymorphism and SLE in multiple ethnic populations. These findings reinforce the value of large sample series for discovery and follow‐up of genetic variants contributing to the aetiology of SLE.     

All-inside versus inside-out meniscal repair: A systematic review and meta-analysis

BackgroundMeniscal repair using all-inside devices has garnered popularity compared to inside-out repair, yet few studies directly compare the two techniques in terms meniscal healing rates, surgical time, patient outcomes and incidence of complications.MethodsA systematic literature review was performed using the Medline, Cochrane and Embase databases. English-language studies comparing all-inside and inside-out arthroscopic meniscal repair techniques directly were included. Randomised controlled trials (RCTs) and observational studies with at least 10 patients in each treatment arm were included. Meta-analyses were performed using a fixed effect (when I2 < 50%) or random effects model (I2 ≥ 50%).ResultsA total of 1042 studies were identified with seven being sui for inclusion (n = 505 patients). These comprised of one RCT two prospective and four retrospective, comparative, observational studies. Meta-analyses demonstrated that there was a significant reduction in operating time favouring all-inside repair (ratio of means [ROM] 0.62, 95% confidence interval [CI] 0.48–0.79; p = 0.0002) based on 3 studies (n = 208 patients). Based on 5 studies (n = 370 patients), there was no significant difference in meniscal healing rates between the groups (OR 1.26, 95% CI 0.52–3.10; p = 0.61). Nerve injury was more common after inside-out repair. There was a 85% reduction in the odds of nerve injury with the all-inside technique (OR 0.15, 95% CI 0.05–0.47; p = 0.0013). A qualitative data analysis suggested no difference in functional outcomes between the two techniques.ConclusionsAll-inside meniscal repair is associated with reduced operative time and a lower odds of nerve injury complications compared to inside-out repair, without compromising meniscal healing or functional results.     

Interleukin-6-174G > C (rs1800795) polymorphism distribution and its association with rheumatoid arthritis: A case-control study and meta-analysis

The association of interleukin-6 (IL-6)-174G?>?C (rs1800795) single nucleotide polymorphism (SNP) with the risk of acquiring rheumatoid arthritis (RA) is a relevant issue because of conflicting and consensus lacking reports published in literature. We investigated IL-6-174G?>?C promoter polymorphism in 34 RA patients, attending a tertiary care hospital in north India. We also performed a meta-analysis, of the previously published studies reporting this genetic relationship, in overall population, and independently in Asian and Caucasian ethnicities to further elucidate this association. A total of 13 studies, including the current one, involving 3291 RA cases and 3812 controls were analyzed. Out of the 13 studies, 6 were from Asian, 6 from Caucasian and 1 from a mixed population. Our case-control study showed significant association of IL-6-174G?>?C SNP with increased RA risk: allelic (OR?=?3.750, 95% CI?=?1.800–7.813, p?<?0.001); dominant (OR?=?2.800, 95% CI?=?1.167–6.721, p?=?0.021); and recessive (OR?=?36.72, 95% CI?=?2.004–672.7, p?=?0.015). The meta-analysis revealed the increased RA risk associated with IL-6-174G?>?C SNP in overall population: allelic (OR?=?1.650, 95% CI?=?1.169–2.329, p?=?0.004); homozygous (OR?=?1.380, 95% CI?=?0.906–2.101, p?=?0.133); heterozygous (OR?=?1.559, 95% CI?=?1.001–2.428, p?=?0.049); dominant (OR?=?1.663, 95% CI?=?1.078–2.567, p?=?0.022); and recessive (OR?=?1.366, 95% CI?=?0.964–1.935, p?=?0.079). Subgroup analysis also showed this polymorphism to be associated with increased RA risk in Asian population: allelic (OR?=?3.724, 95% CI?=?1.361–10.190, p?=?0.010); dominant (OR?=?3.823, 95% CI?=?1.320–11.074, p?=?0.013); and recessive (OR?=?4.357, 95% CI?=?1.634–11.623, p?=?0.003), but not in Caucasian population. This meta-analysis shows that IL-6-174G?>?C SNP is significantly associated with increased RA risk in overall, and specifically in Asian population.     

Cytochrome P450 1A1 (<Emphasis Type="Italic">CYP1A1</Emphasis>) T3801C and A2455G polymorphisms in breast cancer risk: a meta-analysis

The cytochrome P450 1A1 gene (CYP1A1), encoding Phase I metabolic enzymes, appeared to be a candidate gene for breast cancer risk. However, studies on the association between polymorphisms in this gene and breast cancer have yielded conflicting results. We performed a meta-analysis to investigate the association with breast cancer of the CYP1A1 polymorphisms T3801C (9,316 cases and 12,714 controls) and A2455G (9,552 cases and 9,320 controls). In the genotype contrast of A2455G, both additive [GG vs AA, P = 0.04, fixed-effects OR 0.72; 95% CI (0.53–0.99), P = 0.95 for heterogeneity] and recessive [GG vs (GA + AA), P = 0.04, fixed-effects OR 0.73; 95% CI (0.53–0.99), P = 0.97 for heterogeneity] models produced significant results in east-Asians. In pre-menopausal women in a worldwide population, significant association between A2455G and breast cancer was also found using both models [additive model: P = 0.02, fixed-effects OR 0.52; 95% CI (0.29–0.92), P = 0.39 for heterogeneity; recessive model: P = 0.02, fixed-effects OR 0.51; 95% CI (0.29–0.90), P = 0.38 for heterogeneity]. Our meta-analysis suggests that an A2455G G/G genotype is associated with a trend of reduced breast cancer risk, both in east-Asian women and in pre-menopausal women worldwide, while the T3801C C allele might not be a risk factor for breast cancer. Larger scale primary studies are required to further evaluate the interaction of CYP1A1 polymorphisms and breast cancer risk in specific populations.