2q35 rs13387042和8q24 rs13281615单核苷酸多态性与中国东北汉族绝经前妇女乳腺癌风险关系

背景与目的：乳腺癌作为中国女性最常见的恶性肿瘤,每年的新发数量和死亡数量分别占全世界的12.2%和9.6%,但与中国乳腺癌患者明显相关的基因多态位点至今尚不清楚。本研究旨在探讨2q35 rs13387042和8q24 rs13281615单核苷酸多态性与中国北方汉族绝经前妇女乳腺癌风险关系,为预防和治疗乳腺癌提供循证依据。方法：采用多重单碱基延伸单核苷酸多态性分型技术(SNaPshot)分析方法,检测了280例绝经前乳腺癌患者和287例绝经前正常对照者2q35 rs13387042和8q24 rs13281615多态性位点基因型,并比较不同基因型和等位基因与乳腺癌风险的关系。结果：2q35 rs13387042多态性位点基因型频率在乳腺癌和对照样本之间差异有统计学意义(P=0.017);8q24 rs13281615多态性位点基因型频率在乳腺癌和对照样本之间差异无统计学意义(P=0.967)。Logistic回归分析结果显示,对于2q35 rs13387042位点,与GG相比,GA和GA+AA基因型携带者显著增加乳腺癌的患病风险(OR=1.793,95%CI：1.177～2.733,P=0.007;OR=1.691,95%CI：1.122～2.550,P=0.012),而AA携带者与乳腺癌的患病风险无关(OR=0.572,95%CI：0.104～3.153,P=0.521);与G等位基因相比,A等位基因显著增加乳腺癌的患病风险(OR=1.505,95%CI：1.033～2.193,P=0.033)。对于8q24rs13281615位点,与AA相比,AG、GG和AG+GG基因型携带者与乳腺癌的患病风险无关(OR=0.992,95%CI：0.660～1.490,P=0.968;OR=1.047,95%CI：0.642～1.708,P=0.853;OR=1.007,95%CI：0.682～1.487,P=0.971);与A等位基因相比,G等位基因不增加乳腺癌患病风险(OR=1.021,95%CI：0.809～1.288,P=0.863)。结论：本实验证实2q35 rs13387042多态性位点能够增加中国北方汉族绝经前妇女乳腺癌易感风险,而8q24 rs13281615多态性位点与中国北方汉族绝经前妇女乳腺癌易感性无明显相关性。     

rs6983267和rs1447295与北京地区前列腺癌的关联研究

目的:探讨染色体8q24两个单核苷酸多态性位点(SNPs) rs6983267和rs1447295,与北京地区前列腺癌(PCa)的相关性.方法:采用病例-对照研究,入选了154例PCa患者和138名正常对照者,检测2个SNPs在病例组和对照组间的等位基因及基因型的分布情况,并分析危险基因型的累积效应.结果:rs6983267有TT、GT及GG 3种基因型,在病例组的分布分别为33.1％、46.4％及20.5％,在对照组的分布分别为32.6％、48.5％及18.9％;rs1447295也有AA、AC及CC 3种基因型,在病例组的分布分别为3.3％、38.2％及58.6％,在对照组的分布分别为1.5％、32.1％及66.4％.2个SNPs的风险等位基因和基因型频率在病例组和对照组间的分布差异无统计学意义,P＞0.05.与不具有风险基因型的个体相比,具有1个和同时具有2个风险基因型的个体PCa的发病风险虽然分别提高了1.231和1.571倍,但差异无统计学意义,P＞0.05.结论:SNPs rs6983267和rs1447295可能与北京地区PCa的易感性无关.     

肿瘤转移抑制基因NME1多态性与河北地区非小细胞肺癌相关性研究

目的 肿瘤转移抑制基因NME1启动子区的多态位点rs16949649T＞C和rs2302254C＞T与多种恶性肿瘤的侵袭能力及预后相关,但其与非小细胞肺癌(non-small cell lung cancer,NSCLC)的研究报道较少见.本研究探讨NME1基因rs16949649和rs2302254多态性与河北地区NSCLC的相关性.方法 选取2005-10-01-2010-01-31河北医科大学第四医院胸外科手术治疗的190例NSCLC患者以及190名性别与年龄相匹配的同一地区健康对照作为研究对象.应用聚合酶链反应(polymerase chain reaction,PCR)-连接酶检测反应(ligase detection reaction,LDR)的方法进行rs16949649和rs2302254基因分型.应用x2检验比较基因型和等位基因频率在不同组间的分布;非条件Logistic回归模型计算相对风险度的比值比(odds ratio,OR)及95％可信区间(confidential interval,CI);应用SHEsis在线软件构建单倍型并计算单倍型的OR值.结果 对照组NME1基因的rs16949649 TT基因型和rs2302254 CC基因型所占比例分别为40.5％和68.9％,显著高于NSCLC组的27.9％和53.7％,P值分别为0.012和0.007.携带rs16949649 C等位基因的基因型(TC+CC)个体患NSCLC的风险是携带TT基因型个体的1.86倍(95％CI:1.20～2.88),携带rs2302254T等位基因的基因型(CT+TT)个体患NSCLC的风险是携带CC基因型个体的1.94倍(95％CI:1.27～2.96).单倍型分析显示,携带rs16949649 C/rs2302254 T单倍型可显著增加NSCLC的发病风险(OR=1.82,95％CI:1.28～2.58).rs16949649和rs2302254基因型与肿瘤的病理类型、原发瘤大小、TNM分期和肿瘤转移无关,均P＞0.05;但是随着肿瘤转移程度的加重,风险型基因型所占比例出现逐步增高的趋势.结论 NME1基因的rs16949649和rs2302254多态性与河北地区NSCLC的发病风险相关.携带rs16949649 C等位基因的基因型(TC+CC)和携带rs2302254 T等位基因的基因型(CT+TT)可分别增加NSCLC的发病风险;携带rs16949649 C/rs2302254 T单倍型亦可显著增加NSCLC的发病风险.     

miR-196a-2基因多态位点rs11614913与乳腺癌易感性关系的Meta 分析

[目的]分析miR-196a-2基因多态位点rs11614913与乳腺癌易感性的关系.[方法]检索外文数据库Pubmed、Science Direct和中文数据库CNKI、万方,收集截止到2016年5月31日发表的关于miR-196a-2基因多态位点rs11614913与乳腺癌易感关系的病例对照研究,按纳入与排除标准筛选文献,利用Meta分析的方法对各研究数据进行统计学处理及异质性检验,评估发表偏倚并进行敏感性分析.[结果]共纳入15篇研究miR-196a-2基因多态位点rs11614913与乳腺癌易感关系的文献,包括6362例病例和7392例对照,结果显示:等位基因模型(T vs C)、隐形模型(TT vs CC+CT)和相加模型(TT vs CC)与降低乳腺癌发病风险相关,差异均有统计学意义(OR=0.89,95％CI:0.81～0.99;OR=0.83,95％CI:0.72～0.96;OR=0.79,95％CI:0.65～0.97).按种族进行亚组分析后发现,在亚洲人群中,等位基因模型(T vsC)、显性模型(TT+CT vs CC)、隐形模型(TT vs CC+CT)和相加模型(TT vs CC)也与降低乳腺癌发病风险相关(OR=0.85,95％CI:0.75～0.95;OR=0.83,95％CI:0.70～0.99;OR=0.78,95％CI:0.67～0.91;OR=0.72,95％CI:0.57～0.91),其余模型均不能认为与乳腺癌的易感性相关.高加索人群的各遗传模型均与乳腺癌的发病风险无显著相关性.[结论] miR-196a-2基因多态位点rs11614913的T等位基因和TT基因型可能与降低乳腺癌的发病风险相关.     

染色体8q24和17q24区域与中国人列腺癌的关联分析

目的 探索染色体8q24区域(rs620861C、rs1447295A)和17q24区域(rs185996,G)风险等位基因与北方中国人前列腺癌的关联.了解其基因型与前列腺癌患者表型(年龄、肿瘤分期、PSA水平、Gleason评分、有无良性前列腺肥大)的关联,分析基因之间的交互作用.方法 采用病例-对照设计,收集前列腺癌患者临床表型信息；采用PCR-HRM和测序技术对各位点进行了分型,并对基因型在病例组和正常对照组中的分布进行了年龄匹配的病例-对照间比较(病例组:124人,对照组:138人)及基因交互作用分析；对病例组中基因型在不同临床表型中的分布进行了比较.结果 在病例-对照之间三个风险位点的基因型和等位基因频率分布差异未见有统计学意义；在病例组中各位点与前列腺癌表型之间未见有显著性关联；未能检测到三个风险位点之间有交互作用.结论 染色体8q24区域(rs620861C、rs1447295A)和17q24区域(rs185996G)可能与北方中国人患前列腺癌的遗传风险无关联.     

8q24rs13281615单核苷酸多态性与乳腺癌发病风险的Meta分析

目的:探讨8q24 rs13281615单核苷酸多态性(single nucleotide polymorphism,SNP)与乳腺癌发病风险的关系.方法:检索PubMed、Medline、Embase、中国知网(China National Knowledge Infrastructure,CNKI)和万方数字化期刊等中英文数据库.以乳腺癌病例组和对照组人群基因型分布计算粗比值比(odds ratios,OR)和95％可信区间(95％ confidence interval,CI),采用RevMan 5.1软件进行Meta分析和文献偏倚的评估.结果:共纳入7篇研究文献,累积病例22 128例,累积对照29 276例.采用随机效应模型,与野生纯合子(AA)相比,携带杂合子(AG)和突变纯合子(GG)的妇女发生乳腺癌的合并风险上升(OR=1.14,95％CI:1.04～1.25),尤其是欧洲妇女乳腺癌的发病风险增加(OR=1.14,95％CI:1.02～1.28).结论:8q24 rs13281615的G等位基因型可能会增加乳腺癌的发病风险.     

COX-2基因多态性与非贲门胃癌的发病风险关联

目的 检测COX-2基因单核苷酸多态性(SNP) rs689466、rs5275、rs4648308与非贲门胃癌发病风险的关系.方法 采用TaqMan法对288例非贲门胃癌患者和281例健康对照者所检测的3个SNP进行基因分型;采用Haploview软件构建单体型,并用非条件性Logistic回归计算比值比(OR)及其95％可信区间(CI),以评估各等位基因、基因型及单体型与非贲门胃癌发病风险的关系.结果 rs5275C等位基因和rs4648308A等位基因可增加非贲门胃癌的发病风险;rs5275 CT和CC基因型及rs4648308GA基因型可使非贲门胃癌的发病风险增高(rs5275:CT vs.TT:OR=1.458,95％CI:1.015～2.096;CC vs.TT:OR=3.704,95％CI:1.184～11.59; rs4648308:GA vs.GG:OR=3.387,95％CI:1.953～5.872).单体型分析结果显示:单体型ACA与GTG相比,可增加非贲门胃癌发病风险,OR=3.198,95％CI:1.854～5.516.结论 COX-2基因多态性生rs5275、rs4648308与非贲门胃癌发病风险关联.     

染色体11q13.2和8q24常见变异与前列腺癌关联研究

目的探索染色体11q13．2（rs7931342,G）、8q24（rs13252298,G）和8q24（rs7837688,T）的常见变异与北京市区人群PCa患病风险的关联,并了解其与PCa患者中的基因型和临床表型、遗传、膳食习惯、年龄等的关系。方法采用病例一对照设计,包括124例PCa患者和138例年龄匹配的正常对照者,收集PCa患者年龄、临床表型、遗传、膳食习惯等信息,用聚合酶链式反应-高分辨率熔解曲线结合DNA测序技术,检测染色体11q13．2（rs7931342,G）、8q24（rs13252298,G）及8q24（rs7837688,T）基因型及等位基因频率在两组间的分布情况,并探讨各基因与患者的确诊年龄、BMI、Gleason评分、PSA浓度、肿瘤分期等临床特征之间的关联。采用MDR方法进行基因-基因交互作用分析。结果11q13．2（rs7931342,G）、8q24（rs13252298,G）及8q24（rs7837688,T）的基因型、等位基因频率及由8q24（rs13252298,G）和8q24（rs7837688,T）构成的4种单倍型在病例组和对照间组间的分布差异均无显著性（P〉0．05）。基因型一临床表型观察指标关联分析显示：8q24（rs13252298,G）位点与患病年龄和经常食用洋葱相关（P=0．030;P=0．040）,应用Binary Logistic回归分析,发现11q13．2（rs7931342,G）位点PCa发病与BMI指数相关（P=0．020）,8q24（rs13252298,G）位点PCa发病与饮茶、食用豆制品、食用洋葱相关（P=0．003、0．048、0．037）,8q24（rs7837688,T）位点PCa发病与BPH病史或相关症状相关（P=0．039）。3个位点的交互作用分析显示,最佳模型仅包含1个位点（rs7931342,G）,交叉验证一致性为10／10,检验平衡准确度为0．5420,交叉验证检验组P=0．6727。结论11q13．2（rs7931342,G）、8q24（rs13252298,G）和8q24（rs7837688,T）位点可能与前列腺癌的发生无关联。     

室内空气污染、HIF-1α基因单核苷酸多态性与福建汉族肺癌易感性的关系

背景与目的 低氧诱导因子-1α(hypoxia inducible factor 1α,HIF-1α)与肺癌的恶化与转移有关,但HIF-1α的单核苷酸多态性(single nucleotide polymorphisms,SNPs)与肺癌易感性的研究仍较少.本研究旨在探讨室内空气污染、rs2057482多态性与福建汉族肺癌易感性的关系.方法 采用以医院为基础的病例对照设计,选择2006年1月-2012年12月在福建医科大学附属第一医院、协和医院和南京军区福州总医院的胸外科及呼吸内科病理确诊的汉族新发原发性肺癌患者1,096例,选取无肿瘤病史、同期前往医院其他科室探视的患者汉族亲友和社区汉族人群1,110例,进行问卷调查.应用MALDI-TOF-MS技术对所有研究对象HIF-1α基因rs2057482位点多态性进行基因分型.结果携带有HIF-1αrs2057482位点T基因型的人群更容易罹患小细胞癌[TTvs CC的比值比(odds ratio,OR)值为1.725,95%CI:1.047-2.842].调整一般情况和肺癌有关影响因素后,在共显性遗传模型中,暴露于被动吸烟的rs2057482 TT携带者肺癌患病风险是CC携带者的2.195倍(95%CI:1.038-4.643).在显性遗传模型中,有肿瘤家族史的rs2057482 T基因携带者肺癌患病风险是C基因携带者的1.911倍(95%CI:1.121-3.258).在隐性遗传模型中,肺部疾病史的rs2057482Π携带者的肺癌患病风险是TC+CC携带者的0.159倍(95%CI:0.028-0.920).在加性遗传模型中,有肿瘤家族史的rs2057482 TC+Π携带者的肺癌患病风险是CC携带者的1.542倍(95%CI:1.107-2.340).结论HIF-1αrs2057482位点可能与肺癌易感性存在一定关联.     

p73和MDM2基因多态性与卵巢上皮性癌发病风险的相关性

目的:探讨p73和鼠双微基因2(murine double minute 2, MDM2)启动子区单核苷酸多态性(single nucleotide polymorphisms, SNPs)与卵巢上皮性癌发病风险的关系.方法:采用聚合酶链反应-限制性片段长度多态性方法检测257例卵巢上皮性癌患者和257例健康志愿者妇女(对照组)的p73 G4C14/A4T14、MDM2 309T/G和MDM2 Del1518+/-这3个SNPs位点的基因型频率分布情况.结果:p73 G4C14/A4T14多态的等位基因和基因型频率在卵巢癌组和对照组中的分布差异无统计学意义(P=0.55,P=0.20);病例组中MDM2 309T/G SNP的G等位基因频率(46.7%)明显低于对照组(54.7%),2组比较差异有统计学意义(P=0.01),2组间基因型频率差异也有统计学意义(P=0.046);与MDM2 309T/G SNP的T/T基因型相比,T/G+G/G基因型可明显降低卵巢上皮性癌的发病风险[比值比(odds ratio,OR)=0.65, 95%可信区间(confidence interval,CI):0.44～0.97].进一步的分层分析显示,G等位基因携带者主要降低内膜样癌、Ⅲ～Ⅳ期卵巢癌和50岁以上卵巢癌的发病风险(OR=0.53, 95%CI:0.31～0.90; OR=0.62,95%CI:0.40～0.97; OR=0.59,95%CI:0.38～0.92).MDM2 Del1518+/- SNP的基因型和等位基因频率在卵巢癌组和对照组中的分布差异无统计学意义;分层分析显示,携带MDM2 Del1518+/+基因型会增加黏液性卵巢癌和Ⅰ～Ⅱ期卵巢癌的发病风险 (OR=2.01, 95%CI:0.93～4.37; OR=1.64, 95%CI:0.99～2.72).似然比检验发现,p73 G4C14/A4T14和MDM2 309T/G SNPs之间有明显的交互作用(P=0.03).结论:MDM2基因启动子区309T/G多态的G等位基因可能是卵巢上皮性癌发病风险的一个保护因素,且可能与p73 G4C14/A4T14多态间存在交互作用.     

rs10505474 and rs7837328 at 8q24 Cumulatively Confer Risk of Prostate Cancer in Northern Han Chinese

Aims: Genome-wide association studies (GWAS) have identified several risk variants for prostate cancer(pCa) mainly in Europeans, which need to be further verified in other racial groups. We selected six previouslyidentified variants as candidates and to define the association with PCa in Northern Han Chinese. Methods:749 subjects from Beijing and Tianjin in Northern China were included. Six variants (rs10505474, rs7837328,rs4242384, rs7813, rs486907 and rs1058205) were genotyped by high resolution melting (HRM) assays. Theindividual and cumulative contribution for of the risk of PCa and clinical covariates were analyzed. Results:Among the six candidate variants, onlyrs10505474, and rs7837328, both locating at 8q24 region, were associatedwith PCa in our population.rs10505474 (A) was associated with PCa (ORrecessive= 1.56, p=0.006); and rs7837328 (A)was associated with PCa (ORdominant= 1.38, p=0.042/ORrecessive=1.99, p=0.003). Moreover, we observed a cumulativeeffects between them (ptrend=2.58×10-5). The joint population attributable risk showed the two variants mightaccount for 71.85% of PCa risk. In addition, we found the homozygotes of rs10505474 (A) and rs7837328 (A)were associated with PCa clinical covariants (age at onset, tumor stage, respectively) (page=0.046, Ptumorstage =0.048).Conclusion: rs10505474 (A) and rs7387328 (A) at 8q24 are associated with PCa and cumulatively confer risk,suggesting the two variations could determine susceptibility to PCa in the Northern Chinese Han population.     

Association of 8 Loci on Chromosome 8q24 with Prostate Carcinoma Risk in Northern Chinese Men

Multiple genetic studies have confirmed association of 8q24 variants with susceptibility to prostate cancer(PCa). As PCa risk SNPs may also influence disease outcome, we studied here eight 8q24 risk alleles, andevaluated their role in PCa clinical covariates in northern Chinese men. Blood samples and clinical informationwere collected from ethnically Chinese men from Northern China with histologically-confirmed PCa (n=289)and from age-matched normal controls (n=288). Eight 8q24 SNPs were genotyped by polymerase chain reactionhigh-resolution melting analysis in 577 subjects. We examined the prevalence distribution of 8q24 risk alleles andanalyzed the associations between the risk allele and PCa and clinical covariates to infer their impact on aggressivePCa. Three of the eight SNPs were associated with PCa risk in northern Chinese men, including rs16901966 (OR1.31, 95% CI 1.01-1.70, p=0.042), rs1447295 (OR 1.47, 95% CI 1.09-1.98, p=0.011) and rs10090154 (OR 1.55, 95%CI 1.14-2.12, p=0.005). Haplotype analysis based association with the risk alleles revealed significant differencesbetween cases and controls (OR 1.43, 95%CI 0.99-2.06, p=0.049). The risk alleles rs16901966, rs1447295 andrs10090154 were associated with age at diagnosis and tumor stage as compared with controls, while rs16901966was associated with aggressive PCa (OR 1.43, 95% CI 1.01-2.03, p=0.042). The evidence for 8q24 SNPs with PCarisk in northern Chinese men showed rs16901966, rs1447295 and rs10090154 at 8q24 (region 1, region 2) to bestrongly associated with PCa and clinical covariates. The three SNPs at 8q24 could be PCa susceptible geneticmarkers in northern Chinese men.     

8q24 rs4242382 Polymorphism is a Risk Factor for Prostate Cancer among Multi-Ethnic Populations: Evidence from Clinical Detection in China and a Meta-analysis

Background: Evidence supporting an association between the 8q24 rs4242382-A polymorphism andprostate cancer (PCa) risk has been reported in North American and Europe populations, though data fromAsian populations remain limited. We therefore investigated this association by clinical detection in China, andmeta-analysis in Asian, Caucasian and African-American populations. Materials and Methods: Blood samplesand clinical information were collected from ethnically Chinese men from Northern China with histologicallyconfirmedPCa (n=335) and from age-matched normal controls (n=347). The 8q24 (rs4242382) gene polymorphismwas genotyped by polymerase chain reaction-high-resolution melting analysis. We initially analyzed theassociations between the risk allele and PCa and clinical covariates. A meta-analysis was then performed usinggenotyping data from a total of 1,793 PCa cases and 1,864 controls from our study and previously published studiesin American and European populations, to determine the association between PCa and risk genotype. Results:The incidence of the risk allele was higher in PCa cases than controls (0.222 vs 0.140, P=7.3×10-5), suggesting thatthe 8q24 rs4242382-A polymorphism was associated with PCa risk in Chinese men. The genotypes in subjectswere in accordance with a dominant genetic model (ORadj=2.03, 95%CI: 1.42-2.91, Padj=1.1×10-4). Presenceof the risk allele rs4242382-A at 8q24 was also associated with clinical covariates including age at diagnosis ≥65years, prostate specific antigen >10 ng/ml, Gleason score <8, tumor stage and aggressive PCa, compared withthe non-risk genotype (P=4.6×10-5-3.0×10-2). Meta-analysis confirmed the association between 8q24 rs4242382-Apolymorphism and PCa risk (OR=1.62, 95%CI: 1.39-1.88, P=1.0×10-5) across Asian, Caucasian and AfricanAmerican populations. Conclusions: The replicated data suggest that the 8q24 rs4242382-A variation mightbe associated with increased PCa susceptibility in Asian, Caucasian and African American populations. Theseresults imply that this polymorphism may be a useful risk biomarker for PCa in multi-ethnic populations.     

Association of Six Susceptibility Loci with Prostate Cancer in Northern Chinese Men

Background/Aim: Six prostate cancer (PCa) susceptibility loci were identified in a genome-wide associationstudy (GWAS) in populations of European decent. However, the associations of these 6 single-nucleotidepolymorphisms (SNPs) with PCa has remained tobe clarified in men in Northern China. This study aimedto explore the loci associated with PCa risk in a Northern Chinese population. Methods: Blood samples andclinical information of 289 PCa patients and 288 controls from Beijing and Tianjin were collected. All risk SNPswere genotyped using polymerase chain reaction (PCR)-high resolution melting curve technology and genesequencing. Associations between PCa and clinical covariates (age at diagnosis, prostate-specific antigen [PSA],Gleason score, tumor stage, and level of aggressiveness) and frequencies of alleles and genotypes of these SNPswere analyzed using genetic statistics. Results: Among the candidate SNPs, 11p15 (rs7127900, A) was associatedwith PCa risk (P = 0.02, odds ratio [OR] = 1.64, 95% confidence interval [CI] = 1.09–2.46). Genotypes showeddifferences between cases and controls on 11p15 (rs7127900, A), 11q13 (rs7931342, T), and HNF1B (rs4430796,A) (P = 0.03, P = 0.01, and P = 0.04, respectively). The genotype TG on 11q13 (rs7931342, T) was positivelyassociated with an increased Gleason score (P = 0.04, OR = 2.15, 95% CI = 1.02–4.55). Patients carrying TG on17q24 (rs1859962, G) were negatively associated with an increased body mass index (BMI) (P = 0.03, OR = 0.44,95% CI = 0.21–0.92) while those with AG on HNF1B (rs4430796, A) were more likely to have PSA increase (P= 0.002). Conclusion: Our study suggests that 11p15 (rs7127900, A) could be a susceptibility locus associatedwith PCa in Northern Chinese. Genotype TG on 11q13 (rs7931342, T) could be related to an increased Gleasonscore, AG on HNF1B (rs4430796, A) could be associated with PSA increase, and TG on 17q24 (rs1859962, G)could be negatively associated with an increased BMI in Chinese men with PCa.     

Association between single nucleotide polymorphisms on chromosome 17q and the risk of prostate cancer in a Chinese population

In European populations, 7 single nucleotide polymorphisms (SNPs) on chromosome 17q, 3 SNPs on 17q12, and 4 SNPs on 17q24.3 were recently identified to be closely related to the risk of prostate cancer by a genome-wide association study. In Japanese populations, the correlation between 2 SNPs on 17q and the risk of prostate cancer and tumor aggressiveness was also confirmed by a large-scale experiment. However, whether 17q is associated with prostate cancer and its clinical manifestations in Chinese populations is still unknown. Therefore, we conducted a case-control study in a northern Chinese population and tested 2 SNPs, rs4430796 and rs1859962, on 17q in 124 prostate cancer patients and 111 controls using polymerase chain reaction-high resolution melting curve (PCR-HRM) combined with sequencing. We analyzed the association of the 2 SNPs with the risk of prostate cancer as well as patients' lifestyles, onset ages, Gleason scores, PSA levels, and pathologic stages. We found a significant difference in the G allele of SNP rs1859962 (P = 0.035, OR = 1.51, 95% CI = 1.03-2.21) but not in the rs4430796 genotype frequency or allele frequency distribution between prostate cancer patients and the controls (P > 0.05). Neither of the SNPs was significantly associated with the onset age, Gleason score, PSA level, pathologic stage, or other clinical indicators of patients with prostate cancer (P > 0.05). Our results show that polymorphism of the G allele of SNP rs1859962 is associated with the risk of prostate cancer in a Chinese population.     

Racial disparities in the association between variants on 8q24 and prostate cancer: a systematic review and meta-analysis

Recent studies implicate single nucleotide polymorphisms (SNPs) within the 8q24 region as a risk factor for prostate cancer (PCa). New developments suggest that 8q24 encodes regulators of the nearby MYC gene, a known oncogene. In order to better understand the implications of SNPs in this region, we performed meta-analyses, stratified by race, of seven SNPs and one microsatellite marker previously identified as risk loci on the 8q24 region of the genome. In addition, we reviewed the literature examining the possible associations between these polymorphisms and clinicopathological features of PCa. The results of the meta-analyses indicate that rs6983267, rs1447295, rs6983561, rs7837688, rs16901979, and DG8S737 are significantly associated with a higher risk for PCa for at least one race, whereas the variants rs13254738 and rs7000448 are not. The degree of association and frequency of the causative allele varied among men of different races. Though several studies have demonstrated an association between certain 8q24 SNPs and clinicopathological features of the disease, review of this topic revealed conflicting results.     

Chromosome 17q12 variants contribute to risk of early-onset prostate cancer

In a recent genome-wide association study by Gudmundsson and colleagues, two prostate cancer susceptibility loci were identified on chromosome 17q. The first locus, at 17q12, was distinguished by two intronic single-nucleotide polymorphisms (SNPs) in the TCF2 gene (rs4430796 and rs7501939). The second locus was in a gene-poor region of 17q24, where the strongest evidence of association was for SNP rs1859962. To determine if these loci were also associated with hereditary prostate cancer, we genotyped them in a family-based association sample of 403 non-Hispanic white families, including 1,015 men with and without prostate cancer. SNPs rs4430796 and rs7501939, which were in strong linkage disequilibrium (r(2) = 0.68), showed the strongest evidence of prostate cancer association. Using a family-based association test, the A allele of SNP rs4430796 was overtransmitted to affected men (P = 0.006), with an odds ratio of 1.40 (95% confidence interval, 1.09-1.81) under an additive genetic model. Notably, rs4430796 was significantly associated with prostate cancer among men diagnosed at an early (<50 years) but not later age (P = 0.006 versus P = 0.118). Our results confirm the prostate cancer association with SNPs on chromosome 17q12 initially reported by Gudmundsson and colleagues. In addition, our results suggest that the increased risk associated with these SNPs is approximately doubled in individuals predisposed to develop early-onset disease. Importantly, these SNPs do not account for a significant portion of our prior prostate cancer linkage evidence on chromosome 17. Thus, there likely exist one or more additional independent prostate cancer susceptibility loci in this region.     

Susceptibility Loci Associations with Prostate Cancer Risk in Northern Chinese Men

Background: KLK3 gene products, like human prostate-specific antigen (PSA), are important biomarkersin the clinical diagnosis of prostate cancer (PCa). G protein-coupled receptor RFX6, C2orf43 and FOXP4signaling plays important roles in the development of PCa. However, associations of these genes with PCa innorthern Chinese men remain to be detailed. This study aimed to investigate their impact on occurrence andlevel of malignancy. Methods: All subjects were from Beijing and Tianjin, including 266 cases with prostatecancer and 288 normal individuals as controls. We evaluated associations between clinical covariates (age atdiagnosis, prostate specific antigen, Gleason score, tumor stage and aggressive) and 6 candidate PCa risk loci,genotyped by PCR- high resolution melting curve and sequencing methods. Results: Case-control analysis ofallelic frequency of PCa associated with PCa showed that one of the 6 candidate risk loci, rs339331 in the RFX6gene, was associated with reduced risk of prostate cancer (odds ratio (OR) = 0.73, 95% confidence interval(CI) =0.57-0.94, P = 0.013) in northern Chinese men. In addition, subjects with CX (CC+TC) genotypes had adecreased risk for prostrate cancer compared to those carrying the TT homozygote (OR =0.64, 95% CI = 0.45-0.90, P = 0.008). The TT genotype of 13q22 (rs9600079, T) was associated with tumor stage (P=0.044, OR=2.34,95% CI=0.94-5.87). Other SNPs were not significantly associated with clinical covariates in prostate cancer (P> 0.05). Conclusions. rs339331 in the RFX6 gene may be associated with prostate cancer as a susceptibility locusin northern Chinese men.     

Association of four genetic variants with colorectal cancer in Kazakhstan population

The study was conducted to search for polymorphisms located in the 10th chromosome associated with colorectal adenocarcinoma in representatives of the Kazakhstan population. Study was performed with 282 colorectal cancer (CRC) patients and 159 controls. Genotyping of SNPs was performed by QuantStudio 12K Flex PCR. For four significant SNPs inheritance model analysis was performed. Increasing risk of CRC was noted for rs10795668 in log-additive model (OR = 1.45, 95% CI: 1.05–1.99, p = 0.023); for rs1035209 in log-additive model (OR = 1.79, 95% CI: 1.18–2.72, p = 0.003); for rs11190164 in log-additive model (OR = 1.67, 95% CI: 1.17–2.38, p = 0.004). Decreasing risk of CRC was noted for rs10506868 in log-additive model (OR = 0.56, 95% CI: 0.37–0.85, p = 0.006). We detected SNPs that are associated with CRC risk in the Kazakhstan population.