Genetic Association Between CDKN1B rs2066827 Polymorphism and Susceptibility to Cancer

Much attention has been directed to the association between cancer risk and rs2066827 polymorphism of the CDKN1B gene. However, the results are indefinitive and inconclusive. This study was devised to evaluate the hypothesis that rs2066827 polymorphism is associated with the risk of cancer.Computer-based databases (EMBASE, PubMed, and CNKI) were used to seek all case–control studies evaluating rs2066827 polymorphism and susceptibility to cancer. The genetic risk was assessed by calculating pooled odds ratio (OR) with its corresponding 95% confidence interval (CI). Fixed-effects pooled ORs were calculated by the Mantel–Haenszel method (P_h > 0.05), and random-effects pooled ORs were estimated by the DerSimonian–Laird method (P_h < 0.05).Data on rs2066827 polymorphism and cancer risk were available for 9038 cancer cases and 11,596 controls participating in 17 studies. Carriage of a TG genotype was associated with a minor but significant decrease in the risk of cancer (pooled OR 0.92, 95% CI: 0.86–0.99; model, TG vs. TT). We observed a moderately decreased risk of ovarian cancer based on 1829 cases and 2868 controls (pooled OR 0.85, 95% CI: 0.74–0.97; model, TG vs. TT). A slightly deceased risk of cancer was also indicated in Caucasians consisting of 6707 cases and 8279 controls (pooled OR 0.91, 95% CI: 0.85–0.98; model, TG vs. TT).These data suggest that carriage of a TG genotype at rs2066827 polymorphism may be associated with decreased susceptibility to cancer, ovarian cancer in particular.     

hTERT基因多态性与胃癌易感性的研究

人端粒酶逆转录酶(hTERT)作为端粒酶的关键酶参与了包括胃癌在内的多种肿瘤的发生和发展,有研究发现该基因的多个单核苷酸多态性(SNP)位点与多种恶性肿瘤具有不同程度的相关性。目的:探讨hTERT基因rs2853676和rs2853677位点SNP与胃癌遗传易感性的关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法检测297例胃癌、105例萎缩性胃炎和402例对照组患者rs2853676和rs2853677位点的基因多态性,采用病理学检查和~(13)C-尿素呼气试验检测幽门螺杆菌(Hp)感染。结果:胃癌组rs2853676位点AA基因型频率显著高于对照组(15.2%对6.5%,P=0.01),AA基因型携带者患胃癌的风险增加2.47倍(95%CI:1.46~4.16)。三组rs2853677位点CC、TC、TT基因型频率差异无统计学意义。与对照组相比,萎缩性胃炎组和胃癌组Hp感染率显著升高(64.8%、56.9%对40.3%,P均0.01),OR值分别为2.73(95%CI:1.74~4.26)、1.96(95%CI:1.44~2.67)。Logistic回归分析发现,Hp感染与基因突变无明显交互作用。结论:hTERT基因rs2853676基因多态性与胃癌遗传易感性有关,其增加胃癌的风险与Hp感染可能无关。     

Association Between NAT2 Polymorphisms and Lung Cancer Susceptibility

To further investigate the association between NAT2 polymorphisms and lung cancer susceptibility.In terms of phenotypes, we investigated the acetylator status of NAT2 polymorphisms associated with lung cancer risk. Additionally, in view of genotypes, we mainly analyzed 5 single nucleotide polymorphisms (SNPs) in NAT2 gene, namely C282T, A803G, C481T, G590A, and G857A. Twenty-six eligible studies were included in our meta-analysis by searching PubMed, Embase, and CNKI databases. We used odds ratios (ORs) with corresponding 95% confidence intervals (CIs) to evaluate the susceptibility to lung cancer associated with NAT2 polymorphisms.Overall, based on phenotypes, the pooled ORs showed no significant association between NAT2 polymorphisms and lung cancer susceptibility. In the subgroup analyses by ethnicity and source of control, there was still no significant association. In terms of genotypes, overall, no obvious relationship was observed between NAT2 polymorphisms and lung cancer risk. But increased risk of lung cancer was found in association with NAT2 C282T polymorphism (TT vs. CC + TC: OR = 1.58, 95% CI = 1.11–2.25).Our meta-analysis demonstrates that TT genotype in NAT2 C282T polymorphism may be a risk factor for lung cancer susceptibility. Additionally, the acetylator status of 5 SNPs in NAT2 gene may not be associated with lung cancer risk.     

Association Between Epidermal Growth Factor Polymorphism and Esophageal Squamous Cell Carcinoma Susceptibility

Genetic factors are known to be important in the development of esophageal squamous cell carcinoma (ESCC). Epidermal growth factor (EGF) can activate several signaling pathways leading to proliferation, differentiation, and tumorigenesis of epithelial tissues by binding with its receptor. Interindividual variations in EGF production were genetically contributed to EGF +61 G/A polymorphism. The purpose of this study is to investigate the potential association between EGF gene polymorphism and ESCC in a Chinese population. In this study, we analyzed single nucleotide polymorphism of EGF +61 G/A in 158 patients with ESCC and 212 age- and sex-matched controls in a Chinese population using a polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) strategy and DNA sequencing. The variant genotypes of GA/AA were associated with a significantly decreased risk of ESCC compared with the wild-type homozygote GG (OR = 0.657, 95% CI: 0.434–0.996). However, no significant difference was observed between the EGF +61 G/A polymorphism and the risk of ESCC when the analyses were stratified in terms of age, gender, smoking status, different clinical stage, and lymph node status. The EGF +61 G/A polymorphism is associated with ESCC in a Chinese population. Our data suggests that the EGF gene may play a role in the development of ESCC.     

Association of Matrix Metalloproteinase-7 (-181A>G) Polymorphism with Risk of Esophageal Squamous Cell Carcinoma in Kashmir Valley

Background/Aim:

Degradation of the basement membrane and extracellular matrix by matrix metalloproteinases (MMPs) is believed to be an essential step in the complicated process of hematogenous metastasis. Matrix metalloproteinase-7 (MMP-7) is a small secreted proteolytic enzyme with a broad substrate specificity, and its expression has been shown to be associated with tumor invasion and metastasis for various cancers.

Patients and Methods:

To document the role of MMP-7 polymorphism in esophageal carcinogenesis, a case-control study was performed comprising 135 patients with esophageal cancer (EC) and 195 healthy controls. Genotyping was done by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Data were statistically analyzed using χ² - test and logistic regression models.

Results:

Carriers for the MMP-7 (-181A>G) GG were associated with an increased risk for EC [odds ratio (OR = 2.17; 95% confidence interval (CI) = 1.21-3.92; P = 0.010; P_-trend = 0.04]. Also, in a recessive model, our results showed that MMP-7 (-181A>G) GG allele conferred significantly higher risk for EC (OR =2.16; 95% CI = 1.31-3.54; P = 0.003). The high risk due to MMP-7 (-181GG) genotype was limited to squamous cell histology of EC (OR = 2.41; 95% CI = 1.27-4.56; P = 0.007). Although smoking (Hukka) and high consumption of salted tea are independent risk factors for EC, the interaction of MMP-7 (-181A>G) genotypes with these factors did not further modulate the risk of EC.

Conclusions:

In conclusion, our results show that MMP-7 (-181A>G) GG carriers are at a higher risk of esophageal squamous cell carcinoma in Kashmir valley.     

The Association Between TP53 Arg72Pro Polymorphism and Lung Cancer Susceptibility: Evidence from 30,038 Subjects

Background

The TP53 codon 72 polymorphism has been associated with the individual susceptibility to lung cancer. However, the association remains uncertain and varies with ethnicity, smoking status, cancer histology, and stage.

Methods

We performed a meta-analysis to evaluate the relationship between TP53 Arg72Pro polymorphism and lung cancer susceptibility basing on 15,647 lung cancer patients and 14,391 controls from 36 published literatures. We also performed stratified analysis in populations of different ethnicities, smoking statuses, lung cancer stages, and histological types.

Results

The analysis showed a significantly increased lung cancer susceptibility among Pro allele carriers (P < 0.001, odds ratio (OR) = 1.14, 95 % confidence interval (CI) = 1.1–1.19), especially for smokers (P < 0.001, OR = 1.29, 95 % CI = 1.12–1.47). Stratified analysis indicated that Pro72 elevates lung cancer susceptibility in Asians, while it has no effect on lung cancer risk of Caucasians. Moreover, Pro carriers present an increased risk of developing squamous cell carcinoma and adenocarcinoma, instead of large cell carcinoma and small cell carcinoma. Interestingly, patients with the Pro allele seemed to be diagnosed with lung cancer at the early stages (stage I–II, P = 0.008, OR = 1.2, 95 % CI = 1.05–1.37).

Conclusions

Our results suggest that the Pro allele acts as a risk factor for development of lung cancer, especially for smokers and Asians.     

Association Between p53 codon 72 Genetic Polymorphism and Tobacco Use and Lung Cancer Risk

Lung cancer (LCa) is the leading cause of death by cancer in men. Genetic and environmental factors play a synergistic role in its etiology. We explore in 111 lung cancer cases and 133 unrelated noncancer controls the gene-environment interaction (G × E) between p53cd72 polymorphism variants and smoking and the effect on LCa risk in two kinds of case-control designs. We assessed the interaction odds ratio (IOR) using an adjusted unconditional logistic model. We found a significant and positive interaction association between Pro* allele carriers and smoking habits in both case-control and case-only designs: IOR = 3.90 (95% confidence interval [CI] = 1.10–13.81) and 3.05 (95% CI = 1.63–5.72), respectively. These exploratory results suggest a synergistic effect of the smoking habit and the susceptibility of the Pro allele on lung cancer risk compared with each risk factor alone.     

Genetic Association Between Angiotensinogen Polymorphisms and Lung Cancer Risk

Earlier published studies investigating the association between polymorphisms in the angiotensinogen gene and lung cancer risk showed no consistent results. In this study, we have summarized all currently available data to examine the correlation by meta-analysis.Case–control studies addressing the association being examined were identified through Embase, the Cochrane Library, ISI Web of Science (Web of Knowledge), Google Scholar, PubMed, and CNKI databases. Risk of lung cancer (odds ratio [OR] and 95% confidence interval [CI]) was estimated with the fixed or the random effects model assuming homozygous, allele, heterozygous, dominant, and recessive models for all angiotensinogen polymorphisms.We identified a total of 10 articles in this meta-analysis, including 7 for Leu84Phe, 4 for Ile143Val, and 3 for Leu53Leu. In the meta-analysis of Leu84Phe polymorphism, the homozygous model provided an OR of 1.44 (Phe/Phe vs Ile/Ile: OR = 1.44, 95% CI = 1.04–1.99, P values for heterogeneity test (Q-test) [P_Het] = 0.382). The significantly increased risk was similarly indicated in the recessive model (Phe/Phe vs Phe/Ile + Ile/Ile: OR = 1.41, 95% CI = 1.02–1.95, P_Het = 0.381). We also observed a positive association in the Caucasian subgroup. The heterozygous model and the dominant model tested for the Ile143Val polymorphism showed a marginally increased risk (Ile/Val vs Ile/Ile: OR = 1.16, 95% CI = 1.00–1.36, P_Het = 0.323; Val/Val + Ile/Val vs Ile/Ile: OR = 1.15, 95% CI = 0.99–1.34, P_Het = 0.253).These data suggest that Leu84Phe and Ile143Val polymorphisms in the angiotensinogen gene may be useful biomarkers for lung cancer in some specific populations.     

Genetic Association Between Alcohol Withdrawal Symptoms and Polymorphism of CCK Gene Promoter

In the central nervous system, cholecystokinin (CCK) is an important neurotransmitter that gives the influences on firings, anxiety, notiception, and dopamine-related behavior. CCK co-exists in the dopaminergic neurons, interacting with dopamine. In this study, we examined the genetic variant −45 C to T substitution of the CCK gene promoter region among 195 healthy Japanese and 174 patients with alcohol withdrawal syndrome (52 delirium tremens, 39 hallucinosis, 20 seizures, and 92 lack of these symptoms) by using polymerase chain reaction-based single-strand conformational polymorphism analysis. Patients with delirium tremens showed a significantly higher frequency of the variant, compared with the controls (X²= 4.91, p < 0.03), but patients with other symptoms showed no difference. These data suggested that the individuals possessing allelic mutation (−45T) in the promoter region of the CCK gene might be susceptible to delirium tremens caused by alcohol abuse.     

Association between the TLR4 +896A>G (Asp299Gly) Polymorphism and Asthma: A Systematic Review and Meta-Analysis

Objective. To determine whether there is an association between the toll-like receptor 4 (TLR4) +896A>G single nucleotide polymorphism and asthma by conducting a systematic review and meta-analysis. Methods. The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search for relevant studies was performed using PubMed (MEDLINE), Scopus, and HuGE Literature Finder databases with additional consultation of the reference lists of included studies. Summary odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated for the allelic comparison (G vs. A) and the genotypic comparison assuming a dominant genetic model (AG + GG vs. AA). I² statistics were calculated to assess the presence of between-study heterogeneity and funnel plots were inspected for indication of publication bias. Sensitivity analysis was performed to evaluate the influence of individual studies on the overall effect estimates. Results. Meta-analysis of nine studies consisting of 1838 asthma cases and 1764 controls did not find a significant association between TLR4 +896A>G and asthma (genotypic OR = 1.12, 95% CI: 0.91–1.39, p = .27). Between-study heterogeneity was not detected (I² = 0%) and publication bias was not evident. Sensitivity analysis demonstrated the stability of the null association. Conclusions. The meta-analysis findings suggest a lack of direct association between the TLR4 +896A>G polymorphism and asthma, but gene–environment and gene–gene interaction effects and other considerations involving this polymorphism may exist. Therefore, further study is necessary to fully elucidate the role of TLR4 +896A>G in asthma.     

Association Between Plasminogen Activator Inhibitor-1-675 4G/5G Insertion/Deletion Polymorphism and Chronic Obstructive Pulmonary Disease

Molecular pathology of chronic obstructive pulmonary disease (COPD) is still being investigated to discover relationships with disease pathogenesis. Evidence of plasminogen activator inhibitor-1 (PAI-1) overexpression in the sputum and the blood of COPD patients is growing. We aimed to investigate the potential relation between PAI-1 promoter 4G/5G insertion/deletion polymorphism and COPD development. In a case-control study, we genotyped 117 COPD patients and 160 control subjects for PAI-1 promoter 4G/5G polymorphism by an allele-specific polymerase chain reaction analysis. All subjects were male smokers. In the co-dominant model, there was a significant difference in the distribution of 5G/5G, 4G/5G and 4G/4G genotypes between COPD patients and controls (p = 0.002). In the recessive model, carriers of 4G/4G genotype were significantly higher in COPD patients than controls (p = 0.01). Carriers of 4G/4G genotype were at higher risk to develop COPD than those carrying 5G/5G or 4G/5G genotypes (crude odds ratio (OR) = 2.10, 95% confidence interval (CI) = 1.19–3.73, adjusted OR = 2.5, 95% CI = 1.22–3.99). In conclusion, PAI-1 4G/5G genetic variations are associated with COPD development in males.     

亚甲基四氢叶酸还原酶基因多态性与结肠癌发生关系的荟萃分析

背景：亚甲基四氢叶酸还原酶（methylene tetrahydrofolate reductase，MTHFR）基因多态性与结肠癌发生密切相关，目前多数病例对照研究结果表明MTHFR TT型多态性对结肠癌发生具有保护作用．尤其是在叶酸充足和摄人低乙醇的个体。目的：探讨亚甲基四氢叶酸还原酶基因多态性与结肠癌的相关性。方法：通过文献检索收集肿瘤组和非肿瘤组的病例对照研究，剔除不符合要求的文献，在全面文献回顾的基础上进行荟萃分析。结果：共有12篇符合条件的文献纳入分析，荟萃分析结果表明，以野生型677CC的基因型为参照，携带TT基因型个体发生结肠癌的危险性明显下降，OR为0．84（95％CI：0．76～0．94）；1298CC型相对AA型发生结肠癌的危险性为0．85（95％CI：0．72～1．01）。携带677TT基因型同时摄人高叶酸的个体相对于CC／CT基因型伴摄人低叶酸者发生结肠癌的危险性明显下降，OR为0．76（95％CI：0．52～1．10）；摄人高叶酸的1298AA和AC／CC携带者相对于携带AA基因型伴摄人低叶酸者发生结肠癌的危险性显著降低，OR分别为0．78（95％CI：0．63～0．95）和0．78（95％CI：0．64～0．96）。携带677 TT基因型者不论乙醇摄人高低，发生结肠癌的危险性均为0．92，而CC／CT基因型同时摄人高乙醇者发生结肠癌的危险性为1.34（95％CI：0．92～1．95）；1298位点基因多态性与结肠癌危险性似乎同乙醇摄人无多大关联。结论：MTHFR多态性与结肠癌发生危险性有关．677 TT型和高叶酸摄人明显降低肿瘤发生危险性．而高乙醇摄人在677CC／CT基因型个体中有增加结肠癌发生的趋势。     

G蛋白β3亚单位基因C825T多态性与高血压患者的肥胖无关

目的　探讨G蛋白β3亚单位基因C82 5T多态性与原发性高血压患者肥胖的相关关系。 方法　采用聚合酶链反应结合限制性内切酶片段长度多态分析方法检测 14 7例健康人和 32 1例高血压患者的G蛋白 β3亚单位C82 5T多态性 ,并测定高血压患者的体质指数、总胆固醇、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇及空腹血糖浓度。结果　高血压组G蛋白β3亚单位C82 5T多态性中基因型频率 (CC为 2 8.7% ,CT为 5 2 % ,TT为19.3% )、等位基因频率 (C为 5 4 .6 72 % ,T为 4 5 .33% )与正常对照组基因型频率 (CC为 2 7.2 % ,CT为 4 6 .9% ,TT为 2 5 .9% )、等位基因频率 (C为 5 0 .7% ,T为 4 9.3% )比较无显著性差异 (P >0 .0 5 ) ;CC基因型患者的体质指数、血脂水平与CT +TT基因型患者比较无显著性差异 (P >0 .0 5 )。结论　G蛋白 β3亚单位基因C82 5T多态性可能与高血压患者的肥胖无关     

Genetic Association Between CD143 rs4340 Polymorphism and Pneumonia risk: A Meta Analysis

rs4340 polymorphism at intron 16 of the angiotensin-converting enzyme (CD143) gene was reported to repress cough reflex by reducing bradykinin and substance P levels, thus increasing the likelihood to develop pneumonia. There have been different reports regarding the correlation of CD143 rs4340 genotypes with pneumonia risk, which prompted us to perform a meta-analysis to determine the elusive association.We combined multiple keywords to identify the studies addressing the association between CD143 rs4340 genotypes and pneumonia risk covered in the EMBASE, Google Scholar, PubMed, and CNKI databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the risk of pneumonia. The fixed-effects model (FEM) was used.A total of 10 studies were analyzed in this quantitative analysis. We found a strong association between rs4340 single nucleotide polymorphism (SNP) and pneumonia risk using the recessive model (FEM: OR 1.33, 95% CI 1.13–1.57). A significantly increased risk was also indicated under the recessive model in Asian populations (FEM: OR 1.57, 95% CI 1.19–2.07), community-acquired pneumonia (CAP) (FEM: OR 1.31, 95% CI 1.08–1.60), and nosocomial pneumonia (NP) (FEM: OR 1.52, 95% CI 1.06–2.19).Our meta-analysis demonstrates that CD143 rs4340 polymorphism may represent a risk factor for pneumonia.     

内皮型一氧化氮合酶基因4A4B插入多态性与冠心病的相关性

目的探讨内皮型一氧化氮合酶(e NOS)基因4A4B多态性位点与冠心病的相关性。方法采用PCR和凝胶电泳技术检测842例冠心病患者和842例性别和年龄匹配的健康对照者e NOS基因4A4B位点基因型,并分析其与冠心病的关系。结果冠心病组吸烟、糖尿病、高血压、肥胖以及血脂代谢异常患者比例明显高于对照组;对照组4A4B位点基因型频率分布符合Hardy-Weinberg遗传平衡定律;此位点4A等位基因(10.2%比6.9%,OR=2.03,95%CI=1.39~2.44)、AA基因型(3.0%比0.9%,P=0.001,OR=2.08,95%CI=1.45~2.67)和AA+AB基因型(17.4%比13.1%,P=0.045,OR=1.58,5%CI=1.08~1.94)与冠心病显著相关。分层分析结果显示,AA基因型和4A等位基因在吸烟、糖尿病、高血压和肥胖等各分层亚组和饮酒亚组人群中与冠心病呈明显的相关性,而且糖尿病、高血压和肥胖亚组人群中AA基因型和4A等位基因携带者的冠心病发病风险分别是BB基因型和4B等位基因携带者发病风险的2.34、2.59、3.13倍和2.55、2.77和3.10倍。结论 e NOS基因4A4B位点参与冠心病的发病过程,4A等位基因和AA、AA+AB基因型可能是冠心病的遗传易感因子,上述遗传因子可与吸烟、饮酒、糖尿病、高血压和肥胖等因素相互作用,进一步提高冠心病的发病风险。