Association Analysis of GSTP1-rs1695 Polymorphism with the Risk of Oral Cancer: A Literature Review,an Updated Meta- Analysis,and a Structural Assessment

Background: This study aimed to investigate the association of rs1695 polymorphism in glutathione S-transferase P1 (GSTP1) with risk of oral cancer in a meta-analysis which was followed by a bioinformatics approach. Materials and methods: Related articles were collected through a systematic search in PubMed, Google Scholar, and EMBASE databases up to June 2022 and then screened. Finally, seven studies, including 1249 cases of oral cancer and 1861 healthy individuals, were included in our meta-analysis. Seven different genetic models including G vs. A, GG+GA vs. AA, GG vs. GA+AA, GA vs. GG+AA, GG vs. GA, GG vs. AA, and GA vs. AA were used for the calculation of odds ratio and 95% confidence interval in order to assess the association between GSTP1-rs1695 polymorphism and oral cancer risk. Also, the ethnicity-based stratified analyses were performed using the seven mentioned models. Some bioinformatics software was used to investigate the effect of rs1695 polymorphism on the primary, secondary, and three-dimensional structure of GSTP1. Results: Our results showed that rs1695 polymorphism was not associated with the risk of oral cancer in any seven genetic models (G vs. A: OR= 0.9331, 95%CI= 0.6339-1.3737, P= 0.726; GG vs. GA+AA: OR= 0.9112 , 95%CI= 0.6865-1.2093, P= 0.520; GG+GA vs. AA: OR= 0.9006, 95%CI= 0.5522-1.4690, P= 0.675; GA vs. GG+AA: OR= 0.8732, 95%CI= 0.5763-1.3230, P= 0.522; GG vs. AA: OR= 0.9516, 95%CI= 0.5503-1.6456, P= 0.859; GG vs. GA: OR= 1.0645, 95%CI= 0.7891-1.4359, P= 0.683; GA vs. AA: OR= 0.8825, 95%CI= 0.5499-1.4162, P= 0.604). Also, we did not observe any significant associations in ethnicity-based stratified analyses. But bioinformatics studies have shown that this polymorphism can alter the physicochemical properties and secondary structure of the protein. Conclusions: Based on results, the rs1695 polymorphism could not be considered a risk factor for oral cancer.     

Tumor Necrosis Factor-α Gene Polymorphisms and Risk of Oral Cancer: Evidence from a Meta-analysis

Numerous studies have been conducted regarding association between TNF-α and oral cancer risk, but theresults remain controversial. The present meta-analysis is performed to acquire a more precise estimation ofrelationships. Databases of Pubmed, the Cochrane library and the China National Knowledge Internet (CNKI)were retrieved until August 10, 2013. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) werecalculated with fixed- or random-effect models. The heterogeneity assumption was assessed by I-squared test.Among the eight included case-control studies, all were focused on TNF-α-308G>A and four also concernedthe TNF-α-238G>A polymorphism. It was found that oral cancer risk were significant decreased with theTNF-α-308G>A polymorphism in the additive genetic model (GG vs. AA, OR=0.19, 95% CI: [0.04, 1.00],P=0.05, I2=68.9%) and the dominant genetic model (GG+GA vs. AA, OR=0.22, 95% CI: [0.06, 0.82], P=0.03,I2=52.4%); however, no significant association was observed in allele contrast (G vs. A, OR=0.70, 95% CI: [0.23,2.16], P=0.54, I2=95.9%) and recessive genetic models (GG vs. GA+AA, OR=0.72, 95% CI: [0.33, 1.57], P=0.41,I2=93.1%). For the TNF-α-238G>A polymorphism, significant associations with oral cancer risk were found inthe allele contrast (G vs. A, OR=2.75, 95% CI: [1.25, 6.04], P=0.01, I2=0.0%) and recessive genetic models (GGvs. GA+AA, OR=2.23, 95%CI: [1.18, 4.23], P=0.01, I2=0.0%). Conclusively, this meta-analysis indicates thatTNF-α polymorphisms may contribute to the risk of oral cancer. Allele G and the GG+GA genotype of TNF-α-308G>A may decrease the risk of oral cancer, while allele G and the GG genotype of TNF-α-238G>A may causean increase.     

The Cyclin D1 G870A Polymorphism and Colorectal Cancer Susceptibility: A Meta-analysis of 20 Populations

Purpose: Studies of the association between the cyclin D1 (CCND1) G870A genetic polymorphism and riskof colorectal cancer (CRC) have generated conflicting results. In order to derive a more precise estimation, ameta-analysis was here performed. Materials and methods: An extensive search of relevant studies was carriedout as a meta-analysis of twenty studies with 5,975 cases and 8,333 controls. Results: Overall, a significantlyelevated colorectal cancer risk was associated with variant allele 870A when all studies were pooled (AA vs.GG: OR = 1.23, 95%CI = 1.04-1.44; GA vs. GG: OR = 1.13, 95%CI = 1.01-1.26; dominant model: OR = 1.16,95%CI = 1.03-1.31). In the subgroup analysis by ethnicity, significantly increased risks were detected amongCaucasians (AA vs. GG: OR = 1.27, 95%CI = 1.04-1.44; and dominant model: OR = 1.17, 95%CI = 1.02-1.34).With stratification into sporadic CRC and hereditary nonpolyposis colorectal cancer (HNPCC), the formerdemonstrated increased cancer susceptibility (AA vs. GG: OR = 1.24, 95%CI = 1.04-1.48; dominant model:OR = 1.17, 95%CI = 1.04-1.33). However, no significant associations were found in either Asians or HNPCCpatients for any genetic model. Conclusion: The results suggest that the cyclin D1 870A allele is a low-penetrantrisk factor for development of sporadic colorectal cancer, especially among Caucasians.     

CCND1基因G870A位点多态性与宫颈癌易感性的Meta分析

目的:运用Meta分析方法研究CCND1基因G870A位点多态性与宫颈癌易感性的发生风险。方法:检索PubMed和CNKI数据库中有关CCND1基因G870A位点多态性与宫颈癌易感性的相关性研究,根据纳入标准提取文献数据,应用STATA 11.0软件以OR值和95%可信区间为效应指标,进行Meta统计分析,并对发表偏倚及检测敏感性进行检测。结果:纳入9篇对照研究,共计2638例宫颈癌患者和3651例健康对照人群,Meta分析结果显示,总人群中,CCND1基因G870A位点多态性与宫颈癌风险之间没有显著关联(GA vs GG:OR=1.07,95%CI=0.86-1.34,P=0.53,I2=57.6%;AA vs GG:OR=1.09,95%CI=0.79-1.51,P=0.59,I2=75.0%;(GA+AA) vs GG:OR=1.08,95%CI=0.86-1.36,P=0.49,I2=64.6%;AA vs (GG+GA):OR=1.07,95%CI=0.83-1.36,P=0.61,I2=73.3%)。在针对种族和对照人群来源设计的亚组分析中,仍没有发现CCND1基因G870A位点多态性和宫颈癌的发生风险具有相关性。结论:CCND1基因G870A位点多态性可能与宫颈癌的发生无关。     

Association Between the Pre-mir-218 Polymorphism and Cancer Risk in the Chinese Population: a Meta-Analysis

Background: Several recent studies have explored associations between pre-mir-218 polymorphism(rs11134527) and cancer risk. However, published data are still inconclusive. To obtain a more precise estimationof the relationship in the Chinese population, we carried out a meta-analysis for the first time. Materials andMethods: Through retrieval from the PubMed, Medline, Embase, Web of Science databases, China NationalKnowledge Infrastructure and the Chinese BioMedical Literature Database, a total of four studies wereanalyzed with 3,561 cases and 3,628 controls for SNP pre-mir-218 rs11134527. We calculated odds ratios (ORs)and 95% confidence intervals (95%CIs) to explore the strength of associations. Results: The results showedthat the rs11134527 polymorphism was associated with decreased cancer risk in GG versus AA and GG versusAA+AG models tested ( GG vs AA: OR=0.82, 95%CI: 0.71-0.94; GG vs AA+AG: OR=0.84, 95%CI: 0.74-0.96),and significantly decreased cervical cancer risk was observed in GG versus AA and GG versus AA+AG models(GG vs AA: OR=0.79, 95%CI: 0.66-0.94; GG vs AA+AG: OR=0.80, 95%CI: 0.68-0.94). However, no significantassociation between the rs11134527polymorphism and hepatocellular carcinoma risk was observed in allcomparison models tested (AG vs AA: OR=0.94, 95%CI: 0.79-1.11; GG vs AA: OR=0.88, 95%CI: 0.70-1.10;GG+AG vs AA: OR=0.92, 95%CI: 0.79-1.08; GG vs AA+AG: OR=0.91, 95%CI: 0.75-1.11). Conclusion: Thefindings suggest that pre-miR-218 rs11134527 polymorphism may have some relation to cancer development inChinese. However, well-designed studies with larger sample size and more detailed data are needed to confirmthese conclusions.     

The -765G>C Polymorphism in the Cyclooxygenase-2 Gene and Digestive System Cancer: a Meta-analysis

Background: Published data regarding associations between the -765G>C polymorphism in cyclooxygenase-2(COX-2) gene and digestive system cancer risk have been inconclusive. The aim of this study was to comprehensivelyevaluate the genetic risk of the -765G>C polymorphism in the COX-2 gene for digestive system cancer. Materialsand Methods: A search was performed in Pubmed, Medline (Ovid), Embase, CNKI, Weipu, Wanfang and CBMdatabases, covering all studies until Feb 10, 2014. Statistical analysis was performed using Revman5.2. Results:A total of 10,814 cases and 16,174 controls in 38 case-control studies were included in this meta-analysis. Theresults indicated that C allele carriers (GC+CC) had a 20% increased risk of digestive system cancer whencompared with the homozygote GG (odds ratio (OR)=1.20, 95% confidence interval (CI), 1.00-1.44 for GC+CCvs GG). In the subgroup analysis by ethnicity, significant elevated risks were associated with C allele carriers(GC+CC) in Asians (OR = 1.46, 95% CI=1.07-2.01, and p=0.02) and Africans (OR=2.12, 95% CI=1.57-2.87, andp< 0.00001), but not among Caucasians, Americans and mixed groups. For subgroup analysis by cancer type(GC+CC vs GG), significant associations were found between the -765G>C polymorphism and higher risk forgastric cancer (OR=1.64, 95% CI=1.03-2.61, and p=0.04), but not for colorectal cancer, oral cancer, esophagealcancer, and others. Regarding study design (GC+CC vs GG), no significant associations were found in thenpopulation-based case-control (PCC), hospital-based case-control (HCC) and family-based case-control (FCC)studies. Conclusions: This meta-analysis suggested that the -765G>C polymorphism of the COX-2 gene is apotential risk factor for digestive system cancer in Asians and Africans and gastric cancer overall.     

Current Evidence on Associations Between the MMP-7 (-181A>G) Polymorphism and Digestive System Cancer Risk

Matrix metalloproteinases (MMPs) degrade various components of the extracellular matrix and functionalpolymorphisms in encoding genes may contribute to genetic susceptibility to many cancers. Up to now, associationsbetween MMP-7 (-181A>G) and digestive system cancer risk have remained inconclusive. To better understandthe role of the MMP-7 (-181A>G) genotype in digestive cancer development, we conducted this comprehensivemeta-analysis encompassing 3,518 cases and 4,596 controls. Overall, the MMP-7 (-181A>G) polymorphism wasassociated with higher digestive system cancer risk on homozygote comparison (GG vs. AA, OR=1.21, 95% CI =1.12-1.60) and in a dominant model (GG/GA vs. AA, OR=1.16, 95% CI =1.03-1.46). On subgroup analysis, thispolymorphism was significantly linked to higher risks for gastric cancer (GG vs. AA, OR=1.22, 95% CI = 1.02-1.46; GA vs. AA, OR=1.82, 95% CI =1.16-2.87; GG/GA vs. AA, OR=1.13, 95% CI =1.01-1.27; GG vs. GA/AA,OR= 1.25, 95% CI = 1.06-2.39. We also observed increased susceptibility to colorectal cancer and esophagealSCC in both homozygote (OR = 1.13, 95% CI = 1.06-1.26) and heterozygote comparisons (OR = 1.45, 95% CI= 1.11-1.91). In the stratified analysis by controls, significant effects were only observed in population-basedstudies (GA vs. AA, OR=1.16, 95% CI=1.08-1.50; GA/AA vs. GG, OR=1.10, 95% CI=1.01-1.72). According to thesource of ethnicity, a significantly increased risk was found among Asian populations in the homozygote model(GG vs. AA, OR=1.40, 95% CI=1.12–1.69), heterozygote model (GA vs. AA, OR=1.26, 95% CI=1.02–1.51), anddominant model (GG/GA vs. AA, OR=1.18, 95% CI=1.08–1.55). Our findings suggest that the MMP-7 (-181A>G)polymorphism may be a risk factor for digestive system cancer, especially among Asian populations.     

Association of TNF-α-308 and -238 Polymorphisms with Risk of Cervical Cancer: A Meta-analysis

Published data on the associations between tumor necrosis factor-alpha (TNF-α) promoter -308G>A and-238G>A polymorphisms and cervical cancer risk are inconclusive. To derive a more precise estimation of therelationship, a meta-analysis was performed. Data were collected from MEDLINE and PubMed databases.Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated in a fixed/random effect model.13 separate studies including 3294 cases and 3468 controls were involved in the meta-analysis. We found noassociation between TNF-α-308G>A polymorphism and cervical cancer in overall population. In subgroupanalysis, significantly elevated risks were found in Caucasian population (A vs. G: OR = 1.43, 95% CI = 1.00-2.03; AA vs. GG: OR = 2.09, 95% CI = 1.34-3.25; Recessive model: OR = 2.09, 95% CI = 1.35- 3.25) and Africanpopulation (GA vs. GG: OR = 1.53, 95% CI = 1.02-2.30). An association of TNF-α-238G>A polymorphism withcervical cancer was found (A vs. G: OR = 0.61, 95% CI = 0.47-0.78; GA vs. GG: OR = 0.59, 95% CI = 0.45-0.77;Dominant model: OR = 0.59, 95% CI = 0.46-0.77). When stratified by ethnicity, similar association was observedin Caucasian population (A vs. G: OR = 0.62, 95% CI = 0.46-0.84; GA vs. GG: OR = 0.59, 95% CI = 0.43-0.82;Dominant model: OR = 0.60, 95% CI = 0.44-0.83). In summary, this meta-analysis suggests that TNF-α-238Aallele significantly decreased the cervical cancer risk, and the TNF-α-308G>A polymorphism is associated withthe susceptibility to cervical cancer in Caucasian and African population     

N-Acetyltransferase 2 Gene Polymorphisms are Associated with Susceptibility to Cancer: a Meta-analysis

N-acetyltransferase 2 (NAT2) is a polymorphic enzyme that plays an important role in the metabolism ofvarious potential carcinogens. In recent years, a number of studies have been carried out to investigate therelationship between the rs1799930 and rs1799931 polymorphism in NAT2 and cancer risk in multiple populationsfor different types of cancer. However, the results were not consistent. Therefore, we performed a meta-analysisto further explore the relationship between NAT2 polymorphism and the risk of cancer. A total of 21 studiesinvolving 15, 450 subjects for rs1799930 and 13, 011 subjects for rs1799931 were included in this meta-analysis.Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess strength of associations. Wealso evaluated the publication bias and performed a sensitivity analysis. Overall, our results showed an apparentsignificant association between the NAT2 rs1799930 polymorphism and cancer susceptibility in Asians (GAvs. GG: OR=1.22, 95% CI=1.03-1.45; dominant model: OR=1.22, 95% CI=1.03-1.43) and population-basedcontrols (GA vs. GG: OR=1.10, 95% CI=1.01-1.19; dominant model: OR=1.09, 95% CI=1.01-1.18). In contrast,a significant association was observed between the NAT2 rs1799931 G>A polymorphism and decreased cancersusceptibility in overall meta-analysis (AA vs. GG: OR=0.55, 95% CI=0.33-0.93; GA vs. GG: OR=1.00, 95%CI=0.88-1.14; dominant model: OR=0.97, 95% CI=0.86-1.10; recessive model: OR=0.56, 95% CI=0.34-0.94)and the Asian group (AA vs. GG: OR=0.50, 95% CI=0.26-0.94; recessive model, OR=0.50, 95% CI=0.27-0.94).We found that the NAT2 rs1799930 may be a risk factor, while the NAT2 rs1799931 polymorphism is associatedwith a decreased risk of cancer and is likely a protective factor against cancer development.     

Association of Cytotoxic T-lymphocyte Antigen-4 Polymorphisms with Malignant Bone Tumors Risk A Meta-analysis

Background Previous studies have assessed the association between the Cytotoxic T-lymphocyte Antigen- 4(CTLA-4) polymorphism with the risk of malignant bone tumor, but the conclusions were inconsistent. We aimed to clarify association of cytotoxic T-lymphocyte antigen-4 polymorphisms with malignant bone tumors risk by performing a meta-analysis. Materials and Methods The databases including PubMed, EMBase databases and the Cochrane Library were searched to identify the eligible studies prior to January 30 2016. Odds ratio (OR) with 95% con dence interval (95%CI) were used to estimate the strengths of the association between the CTLA-4 polymorphism and the malignant bone tumor risks. The meta-analysis was performed by STATA 12.0. Results Four individual studies with a total of 1003 cases with malignant bone tumor and 1162 controls were included in our meta-analysis. The results of meta-analysis on those data demonstrated that CTLA-4 +49G>A polymorphism was associated with the risk of Ewing's sarcoma and osteosarcoma strongly (A vs. G OR1.36, 95%CI1.20- 1.54, p0.000; AA+AG vs. GG OR1.35, 95%CI1.14-1.61, p0.001; AA vs. GG OR2.24, 95%CI1.67-2.99, p0.000; AA vs. AG+GG OR2.00, 95%CI1.53-2.62, p0.000), but CTLA-4 -318C/T polymorphism was not associated with the risk of malignant bone tumor (C vs. T OR0.76, 95%CI0.76-1.08, p 0.262; CC+CT vs. TT OR0.70, 95%CI0.41-1.20, p0.198; CC vs. TT OR0.69, 95%CI0.40-1.19, p 0.183; CC vs. CT+TT OR0.92, 95%CI0.75-1.13, p 0.419). Subgroup analysis showed that there are signi cantly positive correlations between CTLA-4 +49G>A polymorphism and increased risks of malignant bone tumors in large size of sample (A vs. G OR1.347, 95%CI 1.172,1.548, p0.000; AA vs. GG OR2.228, 95%CI 1.608,3.085, p0.000), Ewing's Sarcoma or Osteosarcoma (A vs. G OR1.361, 95%CI 1.201,1.540, p0.000; AA vs. GG OR2.236, 95%CI 1.674,2.986, p0.000), and PCR-RFLP or Sequencing(A vs. G OR1.361, 95%CI 1.201,1.540, p0.000; AA vs. GG OR2.236, 95%CI 1.674,2.986, p0.000), but CTLA-4 -318C/T polymorphism was not associated with the risk of malignant bone tumors in diagnosis, genotype method, and sample size (all p>0.05). Conclusions CTLA-4 +49A/G variant was associated with an increased risk of developing the malignant bone tumors, such as Ewing's sarcoma and osteosarcoma. However, it failed to show the association between CTLA-4 -318C/T polymorphism and the risk of malignant bone tumors. Future large-scale studies remain to be done to con rm our conclusions.     

The CCND1 G870A Gene Polymorphism and Leukemia or Non-Hodgkin Lymphoma Risk: a Meta-analysis

In recent years, mounting evidence has indicated that the CCND1 G870A gene polymorphism, which impacts the mitotic cell cycle, may influence leukemia or non-Hodgkin lymphoma risk. Unfortunately, the previous results were inconsistent. Therefore, a meta-analysis was performed to obtain a more precise estimation of any association. We conducted a search in PubMed, Embase and CNKI covering all published papers up to March, 2014. A total of 9 publications including 10 case-control studies met the inclusion criteria. Odds ratios (ORs) and their 95% confidence intervals (95%CIs) were applied to assess association. The pooled ORs showed significant association in non-Hodgkin lymphoma (comparison A vs G: OR= 1.114, 95%CI=1.053-1.179, p=0.000; homozygote comparison AA vs GG: OR=1.245, 95%CI=1.110-1.396, p=0.000; heterozygote comparison AG vs GG: OR=1.095, 95%CI=1.000-1.199, p=0.05; dominant model AA/GA vs GG: OR=1.137, 95%CI=1.043-1.239, p=0.003; and recessive model AA vs GA/GG: OR=1.177, 95%CI=1.066-1.301, p=0.001). However, there was no association between the CCND1 G870A polymorphism and leukemia risk. In conclusion, the CCND1 G870A polymorphism may increase risk of non-Hodgkin lymphoma, but not leukemia. However, more primary large scale and well-designed studies are still required to evaluate the interaction of CCND1 G870A polymorphism with leukemia and non-Hodgkin lymphoma risk.     

Association of the XRCC1 c.1178G>A Genetic Polymorphism with Lung Cancer Risk in Chinese

The X-ray repair cross-complementing group 1 protein (XRCC1) plays important roles in the DNA baseexcision repair pathway which may influence the development of lung cancer. This study aimed to evaluatethe potential association of the XRCC1 c.1178G>A genetic polymorphism with lung cancer risk. The createdrestriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods were utilized to evaluatethe XRCC1 c.1178G>A genetic polymorphism among 376 lung cancer patients and 379 controls. Associationsbetween the genetic polymorphism and lung cancer risk were determined with an unconditional logistic regressionmodel. Our data suggested that the distribution of allele and genotype in lung cancer patients was significantlydifferent from that of controls. The XRCC1 c.1178G>A genetic polymorphism was associated with an increasedrisk of lung cancer (AA vs GG: OR=2.91, 95%CI 1.70-4.98, p<0.001; A vs G: OR=1.52, 95%CI 1.22-1.90, p<0.001).The allele A and genotype AA may contribute to risk of lung cancer. These preliminary results suggested thatthe XRCC1 c.1178G>A genetic polymorphism is statistically associated with lung cancer risk in the Chinesepopulation.     

基质金属蛋白酶-7启动子（-181A/G）基因多态性与消化道肿瘤易感性的Meta分析

目的:评价基质金属蛋白酶-7（MMP-7）启动子（-181A/G）基因多态性与消化道肿瘤易感性的关系。方法:计算机检索各大医学数据库,对2017年7月前公开发表的关于MMP-7（-181A/G）基因多态性的病例对照研究进行Meta分析。结果:共19项研究符合纳入标准,累计病例数3 296例,对照组4 362例。从总体效应量分析,除隐性基因模型外,MMP-7（-181A/G）基因多态性与消化道肿瘤易感性有关,差异有统计学意义（G vs A,OR=1.25,95%CI:1.09~1.43,P=0.00;GG/AG vs AA,OR=1.25,95%CI:1.12~1.39,P=0.00;GG vs AA,OR=1.42,95%CI:1.03~1.94,P=0.03;AG vs AA,OR=1.21,95%CI:1.07~1.35,P=0.00）。进一步分层分析表明MMP-7（-181A/G）基因多态性与胃癌、食管鳞癌的易感性有关,但并不能确定是否增加结直肠癌的发生风险。按照种族进行亚组分析,提示MMP-7（-181A/G）基因多态性能够显著增加亚洲人群的消化道肿瘤的发生率。结论:MMP-7（-181A/G）基因多态性与消化道肿瘤有关,G等位基因增加了食管鳞癌、胃癌的发生风险。     

Association between the HSPA1B ±1267A/G Polymorphism and Cancer Risk: a Meta-analysis of 14 Case-Control Studies

Background: Previous epidemiological studies have suggested a potential role of the HSPA1B±1267A/G polymorphism in risk of developing cancer. However, the results were inconsistent. Therefore, we performed this meta-analysis to summarize the possible association with cancer risk. Materials and Methods: We retrieved relevant articles from PubMed, EMBASE, ISI Web of Science, Chinese Biomedical Literature and Chinese National Knowledge Infrastructure. Studies were selected using specific criteria. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess those associations. All analyses were performed using STATA software. Results: Fourteen case-control studies, including 1, 834 cancer cases and 2, 028 controls were included in this meta-analysis. Overall, the results indicated that the G allele of HSPA1B gene ±1267A/G was significantly associated with an increased cancer risk in all genetic models (G vs A: OR=1.51, 95%CI 1.17-1.95, p=0.001; GG vs AA: OR=2.93, 95%CI 1.50-5.74, p=0.002; AG vs AA: OR=1.48, 95%CI 1.10-1.98, p=0.009; GG/AG vs AA: OR=1.69, 95%CI 1.22-2.33, p=0.001; GG vs AG/AA: OR=2.31, 95%CI 1.24-4.32, p=0.009). In the subgroup analysis stratified by ethnicity, a significant association was identified in Caucasians (G vs A: OR=1.35, 95%CI 1.08-1.69, p=0.008; GG/AG vs AA: OR=1.36, 95%CI 1.09-1.70, p=0.007), but not in Asians. In the stratified analysis by cancer types, individuals with the G allele showed an increased risk of hepatocellular carcinoma compared with carriers of the A allele (OR=2.40, 95%CI 1.47-3.91, p< 0.001). Inversely, individuals with the GG genotype showed a decreased risk of gastric cancer compared with carriers of the AG/GG genotypes (GG vs AG/AA: OR=0.39, 95%CI 0.20-0.70, p=0.007). Conclusions: This meta-analysis suggests associations between the HSPA1B ±1267A/G polymorphism and risk of cancer. However, this association might be Caucasian-specific and the G allele of this polymorphism probably increases risk of hepatocellular carcinoma while decreasing risk of gastric cancer. Further well-designed studies based on larger sample sizes are needed to validate these findings.     

MLH1 polymorphisms and cancer risk: a meta-analysis based on 33 case-control studies

Objective: Cumulative evidence suggests that MLH1, the key component in the mismatch pathway, plays an important role in human cancers. Two potential functional polymorphisms (-93G>A and I219V) of MLH1 have been implicated in cancer risk. The aim of this meta-analysis was to summarize the evidence for associations. Methods: Eligible studies were identified by searching the electronic literature PubMed, ScienceDirect and Embase databases for relevant reports and bibliographies. Studies were included if of case-control design investigating MLH1 polymorphisms (-93G>A and I219V) and cancer risk with sufficient raw data for analysis. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to evaluate the strength of associations. Results: Our meta-analysis from 33 published case-control studies showed the variant A allele of -93G>A polymorphism to be associated with increased risk in all genetic models (AA vs. GG: OR = 1.22, 95% CI: 1.03-1.44), especially among non-Asians (AA vs. GG: OR = 1.28, 95% CI: 1.04-1.58). For the I219V polymorphism, however, there was no main effect associated with overall cancer risk in any genetic model. Conclusions: The meta-analysis suggested that the MLH1 -93G>A polymorphism may be a biomarker of cancer susceptibility. Large sample association studies and assessment of gene-to-gene as well as gene-to-environment interactions are required to confirm these findings.     

Association between IL-27 Gene Polymorphisms and Cancer Susceptibility in Asian Population: A Meta-Analysis

Background: Interleukin 27 (IL-27) has potent antitumor activity. Several epidemiological studies have designated that genetic variants of the IL-27 gene may contribute to various cancer susceptibility, but the data were inconclusive.  Objective: The current meta-analysis aimed to address the association between IL-27 rs153109, rs17855750, and rs181206 polymorphisms and the risk of cancer. Data Sources: Our team has selected eligible studies up to May 1, 2020, from several electronic databases, including Web of Science, PubMed, Scopus, and Google Scholar databases. Results: Our meta-analysis revealed that the carriers rs153109 A>G polymorphism in the IL-27 gene have higher risks of diseases in the heterozygous (OR=1.26, 95%CI=1.06-1.49, P=0.007, AG vs AA), homozygous (OR=1.18, 95%CI=1.01-1.37, p=0.33, GG vs AA), dominant (OR=1.25, 95%CI=1.07-1.47, P=0.006, AG+GG vs AA), and allele (OR=1.15, 95%CI=1.04-1.27, P=0.008, G vs A) genetic models. Stratified analysis by cancer type indicated that this variant was significantly associated with gastrointestinal cancer, colorectal cancer and breast cancer. The findings did not support an association between rs17855750 T>G, rs181206 T>C polymorphisms of IL-27 and cancer risk. Conclusion: the current study findings suggest that IL-27 rs153109 polymorphism significantly increased the risk of cancer susceptibility. Well-designed replication in a larger independent genetic association study with larger sample sizes in diverse ethnicities is required to verify the findings.     

Adiponectin Receptor 1 (ADIPOR1) rs1342387 Polymorphism and Risk of Cancer: a Meta-analysis

Many studies have indicated possible associations between a polymorphism of adiponectin receptor 1(ADIPOR1) rs1342387 and risk of cancer, but contradictory results have been reported. The main aim ofthis study was to draw a reliable conclusion about the relationship between the rs1342387 polymorphism andcancer incidence, by conducting a literature search of Pubmed, Embase, Wanfang and Cochrane libraries.Eleven studies including 3, 738 cases and 4, 748 controls were identified in this meta-analysis. The ADIPOR1rs1342387 polymorphism was associated with risk of colorectal cancer for all genetic comparison models (GGvs AA, OR: 1.44, 95%CI: 1.21 -1.70; G carriers vs A carriers, OR: 1.23, 95%CI: 1.11 -1.36; dominant model,OR: 1.28, 95%CI: 1.10 -1.49 and recessive model, OR: 1.31, 95%CI: 1.12 -1.55). Stratified by ethnicity, thers1342387 polymorphism was significantly associated with risk of colorectal cancer in Asian ancestry for allgenetic comparison models (GG vs AA, OR: 1.56, 95%CI: 1.26-1.92; G carriers vs. A carriers OR: 1.30, 95%CI:1.18 -1.43; dominant model OR: 1.31, 95%CI: 1.08 -1.60 and recessive model OR: 1.44, 95%CI: 1.26 -1.64), butnot in Caucasian or mixed (Caucasian mainly) groups. In summary, the ADIPOR1 rs1342387 polymorphism issignificantly associated with risk of colorectal cancer among individuals of Asian ancestry.     

An updated meta-analysis between the association of XRCC1 Arg399Gln polymorphism and hepatocellular carcinoma risk

Background: Various studies have evaluated the relationship between X-ray repair cross-complementinggroup 1 (XRCC1) Arg399Gln polymorphism and hepatocellular carcinoma (HCC) risk, but the conclusionshave been inconsistent and underpowered. The purpose of this updated meta-analysis was to examine whetherXRCC1 Arg399Gln polymorphism confers susceptibility to HCC. Methods: Eligible studies extracted fromPubMed, Embase, Cochrane Library, VIP (chinese) and CNKI (chinese) up to November 2013 were included inthe study. Pooled odds ratio (OR) together with their 95% confidence interval (CI) were estimated to evaluateXRCC1 Arg399Gln polymorphism and HCC risk. Results: Finally, 21 studies with 4,170 cases and 5,030controls were involved in our meta-analysis. The results demonstrated that there was significant associationbetween Arg399Gln polymorphism and HCC risk under two contrast models in overall populations (AG vs GG:OR=1.265, 95%CI=1.036-1.545, p=0.021; AA+AG vs GG: OR=1.240, 95%CI=1.021-1.506, p=0.030). In subgroupanalyses, significant association was found in Asians (A vs G: OR=1.175, 95%CI=1.013-1.362, p=0.033; AG vsGG: OR=1.317, 95%CI=1.070-1.622, p=0.009; AA+AG vs GG: OR=1.289, 95%CI=1.055-1.575, p=0.013) andCaucasians (A vs G: OR=0.591, 95%CI=0.361-0.966, p=0.036; AA+AG vs GG: OR=0.468, 95%CI=0.234-0.934,p=0.031). Conclusions: The results suggest that XRCC1 Arg399Gln polymorphism may increase HCC riskespecially among Asians. However, XRCC1 Arg399Gln polymorphism might act as a protective role againstHCC among Caucasians.     

The 2518 A/G Polymorphism in the MCP-1 Gene and Cancer Risk: A Meta-analysis

Background: The 2518 A/G polymorphism in the MCP-1 gene has been extensively studied for associationswith cancer; however, results from replication studies have been inconsistent. The aim of this investigationwas to determine links with risk of cancer by meta-analysis. Methods: We searched Pubmed, Embase, CNKI,Weipu and Wanfang databases, covering all case-control studies until March, 2013. Statistical analyses wereperformed using the Revman 5.0 software. Results: A total of 11 case-control studies met our inclusion criteria,including 1,422 cases and 2,237 controls. The results indicated that the MCP-1 2518 gene polymorphism had noassociation with cancer risk overall (GG vs.GA+ AA: OR = 0.89, 95%CI = 0.61–1.28, P = 0.52). However, in thesubgroup analysis by ethnicity, a decrease of cancer risk was found in Asian populations (GG vs.GA+ AA: OR =0.79, 95%CI = 0.63–0.99, P = 0.04). Conclusion: This meta-analysis suggested that the 2518A/G polymorphismof MCP-1 gene is associated with risk of cancer among Asian, but not in Caucasian populations.