TGF-β1基因多态性与头颈部肿瘤遗传易感性关系的Meta分析

目的:综合分析TGF-β1基因多态性与头颈部肿瘤遗传易感性之间的关系。方法:按照统一的检索策略,在Pubmed、Embase、万方、CNKI等中英文数据库中全面检索,收集2017年12月31日之前发表的关于TGF-β1基因多态性与头颈部肿瘤易感性关系的相关文献,然后按照纳入及排除标准筛选文献,提取数据和评价质量后应用Stata12.0软件进行数据分析。结果:共纳入10个病例对照研究,分别对包含869T/C位点的8篇,509C/T位点的5篇,915G/C位点的3篇文章进行统计分析。在869T/C研究中我们观察到:病例组1 607例,对照组1 981例,总体分析显示其与头颈部肿瘤之间有关联,OR=1.181,95%CI:1.035~1.348,P=0.014。对不同病种、不同人种、样本量大小进行亚组分析显示,869T/C各基因位点与鼻咽癌和口腔癌这两种病种无关联,与亚裔人种有关联,OR=1.431,95%CI:1.191~1.720,P=0.000。该位点多态性同时与样本量大于100有关联性,OR=1.230,95%CI:1.078~1.404,P=0.002。在509C/T 的5篇研究中:病例组1 355例,对照组1 579例,我们仅分析了鼻咽癌相关的4项研究,很遗憾我们并没有发现该位点与鼻咽癌之间有关联,OR=1.090,95%CI:0.865~1.374,P=0.464。在915G/C位点的3篇研究中我们共收集了病例组340例,对照组368例,均为口腔癌,统计结果显示该位点与口腔癌之间有关联,OR=2.815,95%CI:1.581~5.012,P=0.000。在等位基因和显性基因中显示出有统计学差异（C vs G:OR=3.800,95%CI:1.125~12.843,P=0.032;GC+CC vs GG:OR=5.113,95%CI:1.224~21.367,P=0.025）;其余基因型未显示统计学差异。同时分别对三种基因位点的相关研究进行敏感性分析显示结果稳定,Begger和Egger检验均提示无发表偏倚。结论:Meta分析显示869T/C基因与头颈部肿瘤的遗传易感性相关,在亚组分析中与亚洲人种和样本量大于100有关联性;915G/C等位基因C vs G,显性基因GC+CC vs GG与口腔癌发生有关,但是509C/T基因与头颈部肿瘤遗传易感性无关。     

髓过氧化物酶基因多态性与肺癌遗传易感性的研究

背景与目的:髓过氧化物酶(myeloperoxidase,MPO)基因启动子区域-463bp处存在G/A多态位点,国外研究表明此位点与肺癌遗传易感性有关,但中国人MPO基因型与肺癌易感性关系尚未见报道,本研究拟对此问题作一探讨。方法:采用病例-对照分子流行病学方法,以PCR-RFLP技术检测98例原发性肺癌和112名健康对照MPO基因型,通过比较不同基因型者的比值比(oddsratio,OR)及其95%可信区间(confidenceinterval,CI)分析基因多态性与中国人肺癌易感性的关系。结果:正常人群G/G、G/A、A/A基因型频率分别为47.3%、42.9%和9.8%,肺癌病例组分别为63.3%、33.7%和3.0%,杂合子G/A在两组人群中分布无显著性差异(P>0.05),但病例组A/A基因型频率显著低于对照组(P<0.025)。携带至少一个等位基因A者患肺癌的风险是基因型为G/G者的52.0%(95%CI0.29～0.93)。在吸烟人群中,等位基因A对肺癌易感性的保护作用有显著性意义(OR=0.41,P<0.025),而在非吸烟人群,这种保护作用无显著性意义(P>0.25)。结论:本研究人群MPO基因多态与肺癌遗传易感性相关,等位基因A对吸烟人群的肺癌易感性有保护作用。     

OPN基因多态性与广西壮族人群鼻咽癌易感性的关系

目的研究骨桥蛋白(osteopontin,OPN)基因单核苷酸多态性及其单倍型与广西壮族人群鼻咽癌(nasopharyngeal carcinoma,NPC)易感性的关系。方法采用病例-对照研究方法,收集2010-03-01-2013-03-20入住右江民族医学院附属医院的广西壮族鼻咽癌患者150例,同时随机选取2012-01-01-2012-08-01右江民族医学院附属医院常规体检的广西壮族人150名作为对照。采用单碱基延伸PCR技术和DNA测序法,检测150例广西壮族鼻咽癌患者和150名壮族对照者的OPN基因rs11728697和rs4754位点单核苷酸多态性,并分析OPN基因的单倍型频率。结果在OPN基因rs11728697位点上,携带CT基因型的个体相比携带常见的CC基因型个体罹患鼻咽癌的风险更高,OR=1.78,95%CI为1.05~2.98,χ2=5.863,P=0.033;但TT基因型并不增个体罹患鼻咽癌的风险,OR=0.92,95%CI为0.55~1.77,χ2=0.012,P=0.921。同时,鼻咽癌组在该位点的等位基因型频率与对照组的频率相比差异无统计学意义,OR=1.14,95%CI为0.69~1.45,χ2=0.545,P=0.466。在OPN基因rs4754位点上,对照组和鼻咽癌组的基因型及等位基因型频率分布差异无统计学意义,P>0.05。对照组和鼻咽癌组的单倍型频率分布差异亦无统计学意义,P>0.05。结论在广西壮族人群中,OPN基因rs11728697位点的CT基因型可能增加个体鼻咽癌的易感性,而rs4754位点的多态性与鼻咽癌的易感性无关。     

DNA修复基因XPD G312A多态性与肺癌易感性关系的meta分析

背景与目的已有的研究结果显示DNA修复基因XPD G312A多态位点与肺癌发生存在相关性,但研究结果尚未有一致性结论。本研究旨在通过meta分析的方法,综合评价DNA修复基因XPD G312A多态位点与肺癌发病风险的相关性。方法检索PUBMED、EMBASE、清华CNKI全文数据库、万方全文数据库中XPD基因G312A多态位点与肺癌易感性关系的病例对照研究。对符合纳入标准的研究用meta分析的方法进行数据合并,采用RevMan5.0和STATA11.0评价研究间异质性,计算合并OR值及95%CI。并进行敏感性分析和发表偏倚检验。结果共纳入18项研究,累计病例6554例,对照8322例。总体人群中A等位基因及AA基因型携带者肺癌风险明显升高(A vs G:OR=1.06,95%CI:1.00-1.12;AA vs AG+GG:OR=1.20,95%CI:1.06-1.36;AA vs GG:OR=1.19,95%CI:1.04-1.36)。亚洲人群中,AA基因型携带者肺癌风险明显升高(AA vs AG+GG:OR=7.15,95%CI:1.90-26.94;AA vs GG:OR=7.20,95%CI:1.91-27.15)。高加索人群中,AA基因型携带者肺癌风险升高(AA vs AG+GG:OR=1.15,95%CI:1.01-1.31)。结论XPD312A等位基因为肺癌发生的风险等位基因,AA基因型携带者肺癌风险升高,尤其在亚洲人群这种影响更为明显。     

CYP2D6基因G4268C和ERCC1基因C8092A位点的单核苷酸多态性与肺癌遗传易感性

目的:探讨辽宁地区CYP2D6基因G4268C和ERCC1基因C8092A位点的单核苷酸多态性对肺癌发生的影响。方法:采用病例-对照研究方法,选取肺癌患者和健康对照者各200例。应用KI法快速抽提人外周血基因组DNA,PCR-RFLP的方法检测CYP2D6基因G4268C和ERCC1基因C8092A位点的单核苷酸多态性。结果:G4268/G、G4268/C和C4268/C这3种基因型在病例和对照组的分布频率分别为1.50%、58.00%、40.50%和2.50%、44.00%、53.50%,非C4268/C基因型的个体发生肺癌的风险是C4268/C基因型个体的1.73倍(95%CI=1.02-2.95),在腺癌中OR=2.75(95%CI=1.27-5.94);按吸烟情况进行分层分析后发现不吸烟者及轻度吸烟者中携带非C4268/C基因型的个体患肺癌的风险显著增高,OR值为2.09(95%CI=1.09-4.25)和3.41(95%CI=1.24-9.93);非A8092/A基因型的个体发生肺癌的风险是A8092/A基因型个体的0.98倍(95%CI=0.52-2.17)。结论:C4268/C基因型在不吸烟者和轻度吸烟者中可能作为保护因素而降低肺癌的易感性,ERCC1 C8092A多态性与肺癌易感性无相关性。     

MKK4基因启动子区-1304T>G多态与食管癌易感性研究

目的:探讨MKK4基因-1304T>G位点单核苷酸多态基因型在中国东部人群中的分布及其对食管癌易感性的影响。方法:设计以医院为基础的病例对照研究,进行食管癌患者与对照人群频数匹配,采用聚合酶链反应-限制性片段长度多态性的方法(PCR-RFLP)对571例食管癌患者和785名正常人的MKK4基因-1304T>G位点(rs3826392)进行基因分型。利用Logistic回归分析基因多态性与食管癌发病风险的关联,并校正年龄和性别。结果:MKK4基因-1304T>G位点基因多态性在病例和对照组中分布差异无统计学意义,GG基因型(OR=0.98,95%CI:0.67～1.61),TG基因型(OR=1.12,95%CI:0.90～1.43),P=0.435。结论:MKK4基因-1304T>G位点的单核苷酸多态可能与中国东部人群食管癌易感性无关。     

广东鼻咽癌患者ATM基因127464G/A位点单核苷酸多态性研究

目的:研究ATM基因单核苷酸多态性位点127464G/A与鼻咽癌(nasopharyngeal carcinoma,NPC)的发生关系。方法:应用非变性聚丙烯酰胺凝胶电泳结合测序方法对38例广东NPC患者及40例对照样本ATM基因127464G/A基因分型。结果:在NPC患者及对照个体中G/A杂合型频率分别为57.9%(22/38)、62.5%(25/40),G/G纯合型频率分别为13.2%(5/38)、17.5%(7/40),A/A纯合型频率分别为28.9%(11/38)、20%(8/40)。结论:体细胞ATM基因127464G/A位点变异在广东NPC患者与正常人群中分布差异无统计学意义,推测其与广东NPC的遗传易感性相关性不大。     

DNA修复基因XPA单核苷酸多态性与肺癌遗传易感性的研究

目的研究中国汉族人群核苷酸切除修复基因XPA A23G多态与肺癌遗传易感性的关系.方法采用病例-对照研究方法,以PCR-RFLP技术分析了310例经组织学确诊的肺癌病例和341例按年龄、性别频数配对的非肿瘤医院对照XPA基因A23G多态,比较不同基因型与肺癌风险的关系,并探讨不同环境因素在其中所起的影响.结果XPA基因A23G多态三种基因型在肺癌病人和对照间的分布差异具有显著性(x2=6.607,P=0.037).与携带XPA 23AA基因型者相比较,携带至少一个23G等位基因(即23GG和23AG基因型)的个体肺癌风险降低34%(校正OR=0.66,95%CI=0.44～0.98).分层分析显示,此保护作用在肿瘤家族史阳性者中尤为明显,校正OR为0.31(95%CI=0.13～0.76).结论XPA A23G多态性可能与中国汉族人群肺癌遗传易感性有关,这一相关性有待进一步的体内和体外功能学研究来证实.     

乙醇脱氢酶2和乙醛脱氢酶2基因多态性及饮酒习惯与直肠癌易感性的研究

目的:研究乙醇脱氢酶2(ADH2)、乙醛脱氢酶2(ALDH2)基因多态性与直肠癌易感性的关系。方法:采用病例-对照研究方法,以PCR-DH-PLC检测研究对象的ADH2/ALDH2基因型,比较不同的基因型及生活习惯与直肠癌的关系。结果:1)与不饮酒者相比较,饮酒者患直肠癌的危险性显著增高(OR=2.20,95%CI:1.47～3.28,P=0.000);2)多因素分析结果未发现ADH2、ALDH2各基因型与直肠癌的危险性有关。3)对ADH2、ALDH2基因多态相互作用的分层分析发现,同时携带ADH2A/A和ALDH2G/G基因型者,发生直肠癌的危险性显著增高(性别、年龄和吸烟调整OR=1.82,95%CI:1.07～3.09)。4)在饮酒者中,ADH2A/A、A/G G/G基因型者患直肠癌的调整OR分别为2.56(95%CI:1.38～4.73)和2.10(95%CI:1.15～3.84);ALDH2G/G基因型者发生直肠癌的调整OR为1.82(95%CI:1.07～3.09)。结论:饮酒是直肠癌的危险因素;ADH2A/A与ALDH2G/G基因型在增加直肠癌易感性上有协同作用;ALDH2G/A A/A基因型可减弱饮酒患直肠癌的危险性。     

CYP2D6基因G4268C和ERCC1基因C8092A位点的单核苷酸多态性与肺癌遗传易感性

目的：探讨辽宁地区CYP2D6基因G4268C和ERCC1基因C8092A位点的单核苷酸多态性对肺癌发生的影响。方法：采用病例-对照研究方法,选取肺癌患者和健康对照者各200例。应用KI法快速抽提人外周血基因组DNA,PCR-RFLP的方法检测CYP2D6基因G4268C和ERCC1基因C8092A位点的单核苷酸多态性。结果：G4268/G、G4268/C和C4268/C这3种基因型在病例和对照组的分布频率分别为1.50%、58.00%、40.50%和2.50%、44.00%、53.50%,非C4268/C基因型的个体发生肺癌的风险是C4268/C基因型个体的1.73倍（95%CI=1.02-2.95）,在腺癌中OR=2.75（95%CI=1.27-5.94）;按吸烟情况进行分层分析后发现不吸烟者及轻度吸烟者中携带非C4268/C基因型的个体患肺癌的风险显著增高,OR值为2.09（95%CI=1.09-4.25）和3.41（95%CI=1.24-9.93）;非A8092/A基因型的个体发生肺癌的风险是A8092/A基因型个体的0.98倍（95%CI=0.52-2.17）。结论：C4268/C基因型在不吸烟者和轻度吸烟者中可能作为保护因素而降低肺癌的易感性,ERCC1 C8092A多态性与肺癌易感性无相关性。     

Relationships between genetic polymorphisms in inflammation-related factor gene and the pathogenesis of nasopharyngeal cancer

Our study aims to discuss the association between inflammation-related factors such as single nucleotide polymorphisms (SNPs) with susceptibility and recurrence in nasopharyngeal carcinoma. We used Taqman real-time polymerase chain reaction (PCR) to characterize the genetic variation of five SNPs in 194 nasopharyngeal carcinoma patients and 231 healthy subjects. All statistical analysis is performed with statistical product and service solutions v13.0; odds ratio (OR) value and 95 % confidence interval (CI) were calculated. There is no relationship between TGFβ1 –869 T/C, IL-6 –634C/G, TGFβ1 –509C/T, IL1 –511C/T and nasopharyngeal carcinoma susceptibility. Both single factor and multiple factors analysis showed that IL1a –889 T/T genotype is significantly associated with nasopharyngeal carcinoma in decreasing the risk of nasopharyngeal carcinoma. A highly significant association was found between IL1a –889 T/T genotype and protective genotype as defined by various pathological types. This is more obvious in the protective genotype of the non-keratin-type squamous carcinoma undifferentiated type. We also discovered that genotype G/G and C/G?+?G/G of IL6 –634 gene are associated with reduced recurrence of nasopharyngeal carcinoma. IL1a –889 gene polymorphism and susceptibility is related to nasopharyngeal carcinoma and can potentially decrease the risk of nasopharyngeal carcinoma in the Han Chinese population in north China. IL1-889 TT genotype is protective genotype for nasopharyngeal carcinoma. We have provided evidence that the GG genotype of the IL6 –634 gene is associated with recurrent risk of nasopharyngeal carcinoma. The G allele is the protective gene of nasopharyngeal carcinoma recurrence.     

Association of a haplotype of matrix metalloproteinase (MMP)-1 and MMP-3 polymorphisms with renal cell carcinoma

It has been shown that the matrix metalloproteinase (MMP)-1 promoter polymorphism 1G/2G is associated with an increased risk of developing various cancers including renal cell carcinoma (RCC), and is in linkage disequilibrium (LD) with the MMP-3 promoter polymorphism 5A/6A. These two genes are localized in 11q22 adjacent to each other. However, the relationship between the MMP-3 5A/6A polymorphism and susceptibility to cancer remains ambiguous. In this study, we genotyped eight polymorphisms in the region containing the MMP-1 and MMP-3 genes in 177 healthy subjects, and explored the relationships between RCC and these polymorphisms or haplotypes in 156 RCC cases and 230 age- and gender-matched controls. All the subjects studied were of Japanese descent. There were three polymorphisms that showed stronger LD with the MMP-1 1G/2G promoter variant than with the MMP-3 5A/6A promoter variant. One of these three polymorphisms was present in exon 2 of the MMP-3 gene and caused an amino acid change, Glu45Lys (G/A). When the genotype distribution of Glu45Lys was compared between RCC patients and controls, the frequency of the G/G genotype was significantly higher in the patients [age- and gender-adjusted odds ratio (OR) = 1.81, 95% confidence interval (CI) = 1.20-2.74]. A significant increase in the frequency of the 2G/2G genotype of the MMP-1 1G/2G polymorphism was also observed in the patients (age- and gender-adjusted OR = 1.86, CI = 1.23-2.82), whereas there was no significant difference for the MMP-3 5A/6A polymorphism. As expected based on these genotype-level results, the frequency of the 2G-G haplotype of MMP-1 1G/2G and MMP-3 Glu45Lys (G/A) polymorphisms was significantly higher in the patients than in the controls (crude OR = 1.95, CI = 1.31-2.91). These findings suggest that this haplotype of MMP-1 and MMP-3 variants may be associated with the risk of developing RCC.     

The G801A Polymorphism in the CXCL12 Gene and Risk of Breast Carcinoma: Evidence from a Meta-Analysis Including 2,931 Subjects

More and more evidence indicates that the G801A polymorphism in the CXCL12 gene might be associatedwith susceptibility to breast carcinoma in humans being. However, individually published results havebeen inconsistent. The purpose of this meta-analysis was to investigate the association between the G801Apolymorphism in the CXCL12 gene and breast carcinoma risk. A complete search strategy was done by theelectronic databases including PubMed and Chinese Biomedical Literature Database. A meta-analysis includingseven individual studies was carried out in order to explore the association between the G801A polymorphism inthe CXCL12 gene polymorphisms and breast carcinoma. The pooled odds ratios (ORs) and their corresponding95% confidence intervals (95%CIs) between the G801A polymorphism in the CXCL12 gene and breast carcinomarisk were assessed by the random-effects model. A significant relationship between the G801A polymorphism inthe CXCL12 gene and breast carcinoma was discovered in an allelic genetic model (OR: 1.214, 95%CI: 1.085-1.358, p=0.001), a homozygote model (OR: 1.663, 95%CI: 1.240-2.232, p=0.001), a heterozygote model (OR:1.392, 95%CI: 1.190-1.629, p=0.000), a recessive genetic model (OR: 1.407, 95%CI: 1.060-1.868, p=0.018) and adominant genetic model (OR: 1.427, 95%CI: 1.228-1.659, p=0.000). On sub-group analysis based on ethnicity,significance was observed between the European group and the mixed group. A significant relationship wasfound between the G801A polymorphism in the CXCL12 gene and breast carcinoma risk. Individuals with theA allele of the G801A polymorphism in the CXCL12 gene are under a higher risk for breast carcinoma.     

Genetic polymorphism of gluthation-S transferases and N-acetyl transferases 2 and nasopharyngeal carcinoma: the Tunisia experience

Interindividual differences observed in the metabolism of xenobiotics have been attributed to the genetic polymorphism of genes, which code for enzymes involved in detoxification. This genetic variability seems to be associated with the individual's susceptibility to certain cancers, including nasopharyngeal carcinoma. In this study, we have investigated the genotypic frequencies of DNA polymorphisms of two detoxification's genes: the gluthatione-S-transferase (GST) and the N-acetyl transferase 2 (NAT2). The study has included 45 patients with nasopharyngeal carcinoma compared to 100 healthy Tunisian controls. The presence of the GSTM1 null and GSTT1 null polymorphism was screened by using a multiplex PCR procedure. A PCR-RFLP method was used to detect polymorphism for the most common alleles of the NAT2 gene. Allelic frequencies between the two groups were compared using a chi2 test and odds ratio with 95% confidence intervals were calculated. The results indicate that the genotypic frequency of GSTM10/0 between controls and patients was significantly different. This genotype confers an increased risk of nasopharyngeal carcinoma (Odds Ratio = 2.12, [0.64-4.7]). However, genotypic frequencies of NAT2*6/NAT2*6 were significantly higher in the group of nasopharyngeal carcinoma patients. The calculated Odds Ratio showed an association between this genotype and nasopharyngeal carcinoma. In conclusion, the increase of nasopharyngeal carcinoma risk in Tunisia seems to be associated with GSTM10/0 and NAT2*6/6 genotype.     

基质金属蛋白酶3、7基因多态性与脑星形胶细胞瘤发病风险的关系

背景与目的:基质金属蛋白酶(matrix metalloproteinases,MMPs)是肿瘤发生、侵袭和转移过程中的关键酶之一.MMPs基因启动子区的单核苷酸多态性(single nucleotide polymorphism,SNPs)可通过影响基因的转录和蛋白的表达而影响肿瘤的发生、发展.本研究旨在探索MMP-3、MMP-7启动子区基因多态性与脑星形胶质细胞瘤发病风险的关系.方法:以聚合酶链反应-限制性片段长度多态性分析方法,检测236例成人星形胶质细胞瘤及365例健康对照的MMP-3-1171 5A/6A及MMP-7-181A/G多态性的基因型.结果:(1)MMP-3等位基因型及基因型总体分布在肿瘤患者组和健康对照组之间差异无统计学意义(P＞0.05).根据性别、发病年龄、病理分级进行的分层分析显示,与6A/6A基因型相比,MMP-35A/5A和5A/6A基因型个体患肿瘤的发病风险与其它基因型个体差异无统计学意义:(2)MMP-7基因型在肿瘤患者组及健康对照组中的分布差异有统计学意义(P=0.001).与A/A基因型相比,A/G及G/G基因型可显著增加星形胶质细胞瘤的发病风险,经性别、年龄较正的OR值分别为1.69及2.77(95%CI=1.01～2.84及1.27～6.02).分层分析显示,G/G基因型可使45岁以下人群及男性个体发生星形胶质细胞瘤的风险增加3倍左右,G/G基因型携带者发生Ⅱ～Ⅳ级星形胶质细胞瘤的风险增加3倍左右,且A/G基因型可增加Ⅱ级星形胶质细胞瘤的发病风险约2倍.结论:MMP-7-181A/G多态性可能影响星形胶质细胞瘤的发病风险,而MMP-3-1171 5A/6A多态性与此肿瘤的易感性可能无关.     

Relationship between XPG codon 1104 polymorphism and risk of primary lung cancer

DNA repair plays a critical role in protecting the genome from insults of cancer-causing agents, such as those found in tobacco smoke. Therefore, reduced DNA repair capacity can increase the susceptibility to smoking-related cancers. Recently, several polymorphisms have been identified in the xeroderma pigmentosum group G (XPG) gene, and it is possible that these polymorphisms may affect the DNA repair capacity, thereby modulating cancer susceptibility. We investigated the relationship between the His1104Asp polymorphism in the XPG gene and the risk of lung cancer. The study population consisted of 310 lung cancer patients and 311 healthy controls who were frequency (1:1) matched based on age and sex. The Asp/Asp genotype was more frequent in the controls (28.9%) than in the cases (18.7%) and associated with a significantly decreased risk of lung cancer [adjusted odds ratio (OR) = 0.54, 95% confidence interval (CI) = 0.37-0.80] when the combined His/His and His/Asp genotype was used as the reference. The protective effect of the Asp/Asp genotype against lung cancer was statistically significant in the older subjects (adjusted OR = 0.51, 95% CI = 0.37-0.80), males (adjusted OR = 0.54, 95% CI = 0.35-0.83), and lighter smokers (adjusted OR = 0.48, 95% CI = 0.25-0.94) in a stratification analysis. When the lung cancers were analyzed by histologic type, the Asp/Asp genotype was associated with a significantly decreased risk of squamous cell carcinoma (adjusted OR = 0.55, 95% CI = 0.34-0.88) and small cell lung cancer (adjusted OR = 0.44, 95% CI = 0.20-0.97), but non-significant decreased risk of adenocarcinoma (adjusted OR = 0.64, 95% CI = 0.36-1.12). These results suggest that the XPG codon 1104 polymorphism contributes to genetic susceptibility to lung cancer.     

A polymorphism in FAS gene promoter associated with increased risk of nasopharyngeal carcinoma and correlated with anti-nuclear autoantibodies induction

Loss of FAS (CD95) expression is a common feature of malignant transformation, which has been related to loss of epithelial cell differentiation and loss of sensitivity to apoptosis. We investigated the potential association between FAS promoter polymorphism and the genetic susceptibility to the Epstein-Barr virus (EBV)-related nasopharyngeal carcinoma. The in vivo functional significance of the FAS polymorphism was investigated by assessing the correlation between FAS genotypes and the presence of autoantibodies to cytoskeleton and nuclear antigens frequently detected in nasopharyngeal carcinoma. We determined the FAS polymorphism distributions by RFLP-PCR in 170 patients with nasopharyngeal carcinoma and in 224 sex and age-matched controls. We used ELISA and the immunofluorescence analysis to characterize the presence of IgG autoantibodies to the cytoskeleton and nuclear proteins in patients' sera. A significantly increased risk of nasopharyngeal carcinoma was associated with heterozygote FAS-A/G (OR=2.00, P=0.001) and homozygote FAS-G/G (OR=3.19, P=0.0001) variants. The increased frequency of FAS-G/G genotype is correlated with the presence of anti-nuclear autoantibodies in patients with nasopharyngeal carcinoma (P=0.0298). Our results demonstrated that FAS promoter polymorphism was significantly associated with the nasopharyngeal carcinoma in Tunisians. The anti-nuclear autoantibodies induction was also found to be related to FAS polymorphism. The FAS promoter polymorphism associated not only with the increased risk of nasopharyngeal carcinoma in Tunisians but also with immune response deregulation observed in this cancer.     

Evaluation of Genetic Polymorphisms of N-acetyltransferase 2 and Relation with Chronic Myeloid Leukemia

Objectives: The N-Acetyltransferase 2 (NAT2) gene encodes a key enzyme involved in xenobiotic metabolism, which contributes to the detoxification of numerous cancer therapy-induced products. However, the NAT2 genotype/phenotype is not fully understood and few studies have reported its relationship with CML. The aim of this study was to determine whether its polymorphisms (C481T, G590A, 803A>G and 857G>A) have a role in chronic myeloid leukemia susceptibility (CML) in Sudanese population. Methods: We performed a case- control study. DNA from 200 CML patients and 100 controls was analyzed for the NAT2 polymorphisms using PCR-RFLP assay. Results: The study showed NAT2 polymorphisms 803AG are associated with CML protection by a factor of 2.3, (OR = 0.044, 95% CI: 0.020-0.095, p = 0. 000). The study indicated that the heterozygous (GA) and mutant (AA) variants of the G857A genotype also offer protection, (OR = 0.002, 95% CI: 0.002-0.019, p = 0. 000) and (OR = 0.018, 95% CI: 0.002-0.133, p = 0. 000), respectively. Conclusion: There was no significant difference in CML diagnosis among Sudanese cases with the 481C→T and 590G→A polymorphisms. But patients with the compound NAT2 genotypes 481CT/803 AG, 590AG/ 803AG, 590AG/ 803GG, 590AA/ 803AG and 590GG/ 803AG were found to have a reduced risk. The current study demonstrates that polymorphisms of NAT2 A803G and G857A might also act as protective factors against developing the disease.     

Quantitative assessment of the association between three polymorphisms in FAS and FASL gene and breast cancer risk

FAS and FAS ligand (FASL) play crucial roles in apoptotic signaling, and deregulation of this pathway may facilitate carcinogenesis. Studies on the association between the FAS/FASL polymorphisms (FAS-1377G/A rs2234767, FAS-670A/G rs1800682, and FASL-844C/T rs763110) and breast cancer risk have reported inconsistent results. Therefore, to characterize the relationship between those polymorphisms and breast cancer risk, we undertook a meta-analysis of those studies. Several electronic databases were searched for articles on the FAS/FASL polymorphisms and breast cancer risk. The genotype data were extracted; pooled odds ratios (OR) with 95 % confidence intervals (CIs) were used to estimate the strength of the association. Five studies were eligible for our meta-analysis. Overall, we observed significant associations of the FAS-1377G/A polymorphism with breast cancer susceptibility (AG vs. GG: OR?=?1.15, 95 % CI 1.02–1.30; AA vs. GG: OR?=?1.39, 95 % CI 1.12–1.72; AG/AA vs. GG: OR?=?1.18, 95 % CI, 1.16–1.32; A vs. G: OR?=?1.16, 95 % CI 1.06–1.26), but we did not observe significant association of the Fas-670A/G and FasL-844C/T polymorphisms with breast cancer risk. In the subgroup analysis, we observed that the FAS-1377G/A and FASL-844C/T polymorphisms were associated with breast cancer risk in Chinese but not Whites; we still did not observed association of the FAS-670A/G polymorphism with breast cancer risk. Our meta-analysis revealed that FAS-1377G>A polymorphism was associated with an increased risk of breast cancer. FASL-844C>T polymorphism might be associated with a reduced breast cancer risk in Chinese. However, FAS-670A/G had no any effect on breast carcinogenesis.