DNA修复基因XPD XPC XRCC4基因多态性与结直肠癌易感性的关联性研究

  目的  探讨DNA修复基因XPD rs13181（codon751A/C,Lys751Gln）、rs238406（codon156C/A,Arg156Arg）、XPC rs2279017（i11C/A）和XRCC4 rs3734091（codon247T/C,Ala247Ser）的单核苷酸多态性与结直肠癌易感性的关系。  方法  采用TaqMan技术对2013年4月至2016年1月北京肿瘤医院收治的338例结直肠癌患者（病例组）和315例健康者（对照组）进行多态位点基因型的检测。  结果  XPD rs13181基因型GT和等位基因G增加个体结直肠癌的发病风险（GT>TT,adjusted OR=1.69,95%CI:1.15~2.47,P=0.007;G>T,adjusted OR=1.77,95%CI:1.19~2.64,P=0.005）;XRCC4 rs3734091基因型GT和等位基因T增加个体结直肠癌的易感性（GT>GG,adjusted OR=9.02,95%CI:5.61~14.50,P＜0.001;T>G,adjusted OR=4.06,95%CI:2.49~6.61,P＜0.001）;XPD rs13181和rs238406的单倍体型GT显著降低结直肠癌的发病风险（adjusted OR=0.39,95%CI:0.18~0.85,P=0.018）。XPCrs2279017等位基因G和XRCC4 rs3734091等位基因T的联合效应（adjusted OR=28.43,95%CI:6.85~117.95,P＜0.001）以及XPD rs13181等位基因G和XRCC4 rs3734091等位基因T的联合效应（adjusted OR=10.24,95%CI:4.69~22.35,P＜0.001）显著增加个体结直肠癌的易感性。  结论  XPD rs13181和XRCC4 rs3734091位点的多态性与结直肠癌的易感性相关。      

rs4779584 C/T、rs4444235 T/C单核苷酸多态性与江苏泰州地区结直肠癌的发病风险研究

目的 了解单核苷酸多态性（SNP）与泰州地区人群中结直肠癌发病的关系。方法 收集泰州人民医院的76例结肠癌、84例直肠癌患者外周血样本作为疾病组,另选170例健康体检正常人群外周血样本作为对照组,选取与结直肠癌高度相关的SNP位点（rs4779584和rs4444235）进行检测,分析不同基因型和等位基因分布情况及其与结直肠癌总体和不同部位的患病风险。结果 两组rs4779584 C/T和rs4444235 T/C基因型分布均符合Hardy-Weinberg平衡。疾病组rs4779584 C/T和rs4444235 T/C的基因型和等位基因分布与对照组相比,差异均有统计学意义（P<0.05）。rs4779584 C/T中,以CC基因型为参照,CT和TT基因型与结直肠癌的患病风险无关联;以CC+CT基因型为参照,TT基因型的结直肠癌患病风险升高,以C等位基因为参照,T等位基因的结直肠癌患病风险升高,差异均有统计学意义（P<0.05）。rs4444235 T/C中,以TT、TT+TC基因型为参照,CC基因型的结直肠癌患病风险均升高;以T等位基因为参照,C等位基因的结直肠癌的患病风险升高,差异均有统计学意义（P<0.05）。结论 在江苏泰州地区人群中,rs4779584和rs4444235 位点SNP与结直肠肿瘤发病风险高度相关。     

miR-155侧翼序列rs767649A/T多态性与结直肠癌的相关性分析

摘 要：［目的］分析miR-155侧翼序列rs767649A/T多态性与结直肠癌的相关性。［方法］ 收集154例结直肠癌和203名健康对照人群外周静脉血样本,TaqMan探针法分析rs767649A/T多态性。［结果］ TT基因型显著增加了结直肠癌的发病风险（TT与AA相比：OR=2.11,95%CI：1.12～3.98,P=0.02;TT与AA/AT相比：OR=1.92,95%CI：1.09～3.38,P=0.02）。与A等位基因对比,T等位基因显著增加了结直肠癌的发病风险（OR=1.40,95%CI：1.04～1.90,P=0.03）。分层分析显示,rs767649A/T多态性与结直肠癌临床分期、分化程度和淋巴结转移等临床特征均无关。［结论］　miR-155侧翼序列rs767649A/T多态性可能是结直肠癌发病的危险因素。     

B7-H1基因rs4143815位点多态性与结直肠癌发病风险的关联研究

目的：B7-H1是肿瘤免疫治疗的一个靶点,位于其3'-非翻译区的rs4143815位点C/G多态性可影响其与miR-570的结合,进而影响B7-H1的表达。本研究旨在探讨B7-H1基因rs4143815位点多态性与结直肠癌发病风险的相关性。方法：采集215例结直肠癌患者和236例年龄性别匹配的健康对照人群外周静脉血,并收集手术切除结直肠癌和癌旁正常组织样本65例,直接测序法检测B7-H1基因rs4143815多态性,运用卡方检验分析B7-H1基因rs4143815多态性与结直肠癌发病风险的相关性;定量PCR检测B7-H1 mRNA表达。结果：结直肠癌和对照组中均检测到B7-H1基因rs4143815多态性的3种基因型,即CC、CG和GG基因型。结直肠癌和癌旁正常组织中均检测到B7-H1 mRNA的表达。与CC基因型相比,GG和CG/GG基因型显著增加了结直肠癌的发病风险[GG与CC相比：OR_调整=1.99,95% CI （1.19,3.34）,P=0.008;CG/GG与CC相比：OR_调整=1.58,95% CI （1.06,2.36） P=0.02]。与C等位基因相比,G等位基因显著增加了结直肠癌的发病风险[OR_调整=1.48,95% CI （1.14,1.93）,P=0.004]。B7-H1 mRNA在结直肠癌组织中的表达明显高于癌旁组织（P=0.02）,并且B7-H1基因rs4143815位点GG基因型携带者B7-H1 mRNA水平明显高于CC基因型携带者（P=0.03）。结论：B7-H1基因rs4143815位点GG基因型可能通过增加B7-H1 mRNA表达,进而增加了结直肠癌的发病风险。     

APC基因3'-非编码区rs1804197多态性与结直肠癌易感性的关系

目的 探讨结肠腺瘤性息肉病(APC)基因3'-非编码区rs1804197多态性与结直肠癌易感性的关系.方法 收集573例结直肠癌病例及588例对照外周静脉血标本,提取外周血DNA,使用实时荧光定量PCR进行基因分型,通过病例-对照研究方法分析rs1804197多态性位点不同基因型与结直肠癌易感性的关系.结果 结直肠癌病例组中rs1804197位点CC型387例(67.5％),AC型153例(26.7％),AA型33例(5.8％);对照组中CC型427例(72.6％),AC型144例(24.5％),AA型17例(2.9％);病例组与对照组中AA基因型比例差异有统计学意义(OR=2.14,95％ CI为1.17 ～3.91,P=0.011),A等位基因频率差异有统计学意义(P=0.011).进一步亚组分析显示,男性人群和不饮酒的人群中,病例组和对照组之间rs18041797位点基因型的频率分布差异具有统计学意义(P男性=0.048,P不饮酒=0.020);在男性人群中,携带A等位基因的个体罹患结直肠癌的风险增加了0.41倍(OR=1.41,95％ CI为1.01 ～ 1.98);在不饮酒的人群中,携带A等位基因的个体罹患结直肠癌的风险增加了0.22倍,但该结果并无统计学意义(OR=1.22,95％ CI为0.91 ～1.64).结论 APC基因3'-非编码区的rs1804197多态性与结直肠癌易感性相关,AA基因型可能增加部分人群中结直肠癌的易感性.     

红细胞补体受体1单核苷酸多态性与肝细胞癌发病风险的研究

目的 探讨红细胞补体受体1（CR1）单核苷酸多态性（SNP）与肝细胞癌（HCC）发病的关系。方法 收集102例HCC患者（HCC组）和98例健康体检者（对照组）的外周血样本,选取CR1的5个标签SNP位点（rs4844600 G＞A、rs17048010 T＞C、rs3818361 C＞T、rs11118167 T＞C和rs9429945 C＞T）进行检测,分析两组的红细胞CR1基因各SNP位点基因型、等位基因及单体型的分布差异及其与HCC患病风险的关系。同时按照性别、年龄相匹配的原则分别从对照组和HCC组中选取52例和53例样本采用流式细胞术检测其红细胞CR1的几何平均荧光强度比值（GMFIR）。结果 两组rs4844600 G＞A基因型和等位基因分布的差异有统计学意义（P＜0.01）。CR1基因rs4844600 G＞A／GG基因型携带者患HCC的风险为非携带者的2.458倍（95％ CI：1.357～4.451）,GA基因型携带者患病风险是非携带者的0.404倍（95％CI：0.218～0.746）,其等位基因G携带者患病风险为非携带者的1.945倍（95％CI：1.183～3.199）。rs17048010 T＞C、rs3818361 C＞T、rs11118167 T＞C、rs9429945 C＞T这4个SNP位点和rs11118167-rs3818361-rs17048010／TCT、TTC、CCT、TTT这4种单体型与HCC的患病风险无关（P＞0.05）。HCC组CR1的GMFIR水平为3.257±1.191,高于HCC组的2.652±0.789,差异有统计学意义（t=2.644,P=0.008）。结论 HCC患者红细胞免疫功能降低,CR1基因SNP位点rs4844600 G＞A与HCC发病关联。     

云南省汉族人群TNF-α基因多态性与非小细胞肺癌发生、发展的相关性

背景与目的：肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）不仅是一种重要的炎症因子,还与肿瘤的发生、发展密切相关。探讨TNF-α基因多态性与云南省汉族人群非小细胞肺癌（non-small cell lung cancer,NSCLC）发生、发展的相关性。方法：选取云南省425例汉族人群NSCLC病例和438名健康体检者,采用TaqMan探针基因分型法对TNF-α基因启动子区域5个单核苷酸多态性（single nucleotide polymorphism,SNP）位点rs1799964（-1031T>C）、rs1800630（-863C>A）、rs1799724（-857C>T）、rs1800629（-308G>A）和rs361525（-238G>A）进行基因分型并分析其等位基因、基因型及所构建的单倍型在NSCLC病例及健康对照者中的频率差异。结果：TNF-α基因启动子5个SNP位点的等位基因和基因型频率在NSCLC病例组和对照组间差异无统计学意义（P＞0.05）。病例分层分析发现,rs1799724（C>T）的T等位基因在腺癌组中的频率显著高于对照组（P=0.010,OR=1.56,95% CI：1.11~2.19）,在显性模式下携带T等位基因的个体（TT+CT）患肺腺癌的风险显著升高（P=0.007,OR=1.66,95% CI：1.15~2.42）。rs1800630（C>A）的A等位基因在腺鳞癌及其他类型肺癌组中的频率显著高于对照组,差异有统计学意义（P=0.013,OR=2.15,95% CI：1.16~3.96）。单倍型分析结果显示,单倍型rs1799724T-rs1800629G在腺癌组中的频率显著高于对照组（P=0.048,OR=1.42,95% CI：1.00~2.01）。结论：位于TNF-α基因启动子区域的SNP位点rs1799724（C>T）等位基因T和基因型TT可能是云南省汉族人群NSCLC中腺癌发生的风险性因素。SNP位点rs1800630（C>A）等位基因A可能是云南省汉族人群NSCLC中腺鳞癌及其他类型肺癌发生的风险性因素。     

晚期结直肠癌中DNMT3b基因多态性与FOLFOX4方案化疗疗效的关系

目的 探讨DNA甲基转移酶3b（DNMT3b）基因单核苷酸多态性（SNPs）与晚期结直肠癌患者应用FOLFOX4方案化疗疗效的关系。方法 采用SNP预测软件筛选HapMap数据库中国汉族人群DNMT3b基因的4个标签SNPs（rs6119954、rs4911107、rs4911259、rs8118663）及启动子区2个SNPs（rs1569686、rs2424913）,采用直接测序法检测178例晚期结直肠癌患者外周血DNA中以上SNPs位点的基因分布情况;采用RECIST 1.1标准评价以上患者接受FOLFOX方案化疗4个周期的近期疗效,并将患者分为有效组（CR+PR）和无效组（SD+PD）,分析不同化疗效果与临床病理参数（年龄、性别、部位、肿瘤大小、病理类型和分化程度）及以上SNPs位点基因型、等位基因的关系。结果 178例晚期结直肠癌患者DNMT3b rs6119954、rs1569686、rs4911107、rs4911259、rs8118663和rs2424913基因多态性位点各基因型分布与预测值的差异均无统计学意义（P>0.05）,符合Hardy-Weinberg平衡。178例晚期结直肠癌患者经4个周期化疗后,获CR 4例、PR 45例、SD 88例、PD 41例,故分为有效49例和无效129例。FOLFOX4化疗效果与年龄、性别、部位、肿瘤大小及病理类型均无关,而与分化程度有关（P<0.05）。rs6119954及rs2424913中携带突变等位基因者的化疗有效率较低,且化疗无效的风险升高,以上差异均有统计学意义（P<0.05）;其余SNPs位点基因分布与疗效及无效风险均无关（P>0.05）。结论 DNMT3b rs6119954及rs2424913与晚期结直肠癌患者FOLFOX4方案的疗效有关,且携带rs6119954 A或rs2424913 T等位基因者化疗无效的风险较高,对于预测晚期结直肠癌患者FOLFOX4方案的效果可能具有一定价值。     

SMAD4基因单核苷酸多态性位点rs12958604和rs10502913与宫颈癌相关性研究

  目的  探讨SMAD4基因单核苷酸多态性（single nucleotide polymorphism,SNP）位点rs12958604和rs10502913与宫颈癌遗传易感性之间的关系。  方法  收集2018年2月至2019年12月右江民族医学院附属医院和广西医科大学附属肿瘤医院确诊的宫颈癌患者和健康体检者血液样本各342例及其临床病理资料,分为宫颈癌组和对照组,采用DNA测序法和SNaPshot技术检测SNP ,分析比较两组rs12958604和rs10502913基因型、等位基因、基因模型、单倍型差异性。  结果  两组SMAD4的rs10502913基因型及等位基因进行比较差异均无统计学意义（均P>0.05）,两组SMAD4的rs12958604 GG基因型和GG+GA显性模型及G等位基因进行比较差异均具有统计学意义（OR=0.577,95%Cl:0.380～0.877,P=0.010; OR=0.670,95%Cl:0.483～0.928,P=0.016 及OR=0.743,95%Cl:0.600～0.920,P=0.006）。单倍型分析显示G-A和G-G在两组中差异均具有统计学意义（均P<0.05）。多元Logistic回归多因素分析显示高血压是独立危险因素。  结论  SMAD4基因SNP位点rs12958604与宫颈癌易感性可能存在关联。      

COX-2 单核苷酸多态性与胃癌生物学行为相关性研究

目的:研究胃癌患者外周血中环氧化酶-2(COX-2)启动子区域-1195G>A 位点单核苷酸多态性(SNP)与其生物学行为之间的相关性.方法:应用q-PCR方法检测118例胃癌患者外周血COX-2基因型,并分析其与生物学行为之间的关系.结果:含有A等位基因的GA+AA基因型相对于GG基因型,肿瘤大小、浸润深度差异显著(P=0.035及P=0.031).结论:胃癌患者COX-2 -1195G>A多态性与肿瘤大小、浸润深度以及免疫组化密切相关.该位点A等位基因提示肿瘤大,浸润深度深以及免疫组化阳性高风险.     

TIM-3基因多态性与肝细胞癌的关联性研究

目的:分析TIM-3 rs4704853、rs1036199和rs10515746基因多态性是否与肝细胞癌（HCC）易感性存在关联。方法:纳入HCC患者342例,健康对照组350例。采用血液基因组提取试剂盒（离心柱法）提取全基因组DNA。SNP分型采用多重扩增及高通量测序技术,采用多元Logistic回归方法分析TIM-3基因多态性与HCC易感性的关联性;采用多个独立样本秩和检验分析TIM-3基因多态性与HCC临床指标的关联。结果:TIM-3基因rs4704853、rs1036199和rs10515746存在完全连锁不平衡,以上3个SNP位点杂合子（OR=6.378,95%CI=1.414~28.776,P=0.016）或突变等位基因（OR=6.270,95%CI=1.396~28.165,P=0.017）患肝癌风险增加,且杂合子组血清TBA（总胆汁酸）水平明显高于野生纯合子组（P＜0.05）。结论:TIM-3 rs4704853、rs1036199和rs10515746基因多态性可能与HCC的发生和TBA水平具有关联性。     

miR-520a靶基因PIK3CA结合位点多态性与中国汉族人群大肠癌易感性的关联研究

背景与目的：越来越多的研究表明,微小RNA(microRNA,miRNA,miR)靶基因位点的多态性可能会影响miRNA的转录或生成能力,影响个体对肿瘤的易感性。本研究旨在探讨大肠癌患者miR-520a靶基因PIK3CA 3 ’端单核苷酸多态性(single nucleotide polymorphism,SNP)位点rs141178472与中国汉族人群大肠癌易感性之间的关系。方法：选取386例大肠癌标本作为实验组,394名年龄及性别比例匹配的非肿瘤个体作为对照组。病例对照研究检测rs141178472的分布频率。统计分析大肠癌易感性与多态性之间的关系。结果：携有rs141178472 CC基因型或C等位基因显著增加了大肠癌的发病风险(CC vs TT,OR=1.716,95%CI：1.084~2.716,P=0.022;C vs T,OR=1.258,95%CI：1.021~1.551,P=0.033)。通过检测大肠癌患者外周血单个核细胞PIK3CA的表达发现,PIK3CA mRNA的表达与SNP基因型rs141178472具有关联性。结论：miR-520a与PIK3CA 3’UTR的SNP位点rs141178472相互作用可能与大肠癌易感性有关。     

FGFR1基因单核苷酸多态性与中国北方汉族女性乳腺癌发病风险及临床病理特征的关系

目的:探究成纤维生长因子受体1（fibroblast growth factor receptor-1,FGFR1)基因单核苷酸多态性与中国北方汉族女性乳腺癌发病风险和临床病理特征的相关性。方法:采用多重单碱基延伸单核苷酸多态性分型技术检测747例乳腺癌患者和716例健康女性人群FGFR1基因rs13317和rs3213849多态位点基因型,并比较不同基因型与乳腺癌发病风险和临床病理特征的关系。结果:FGFR1基因rs13317和rs3213849多态位点基因型频率在乳腺癌组和对照组中的分布无统计学差异(P＞0.05)。与TT基因型携带者相比,rs13317位点的CT基因型、CC基因型和CT+CC基因型携带者与乳腺癌发病风险无关(P=0.464、P=0.136、P=0.103)。与GG基因型携带者相比,rs3213849位点的GA基因型、AA基因型和GA+AA基因型携带者与乳腺癌发病风险无关(P=0.642、P=0.222、P=0.416)。临床病理分析结果显示,rs13317位点多态性与乳腺癌患者的临床分期、肿瘤大小、组织学分级、淋巴结转移、ER、PR、HER2、Ki67及p53无关(P＞0.05)。在共显性模型下,rs3213849位点在Ki67分布上可能存在差异(P=0.055);在显性模型下,rs3213849位点与Ki67表达情况具有相关性(P=0.023),与其他临床病理因素之间均不相关(P＞0.05)。结论:在目前的样本条件下,FGFR1基因rs3213849位点与Ki67表达可能相关,而rs13317和rs3213849多态性与中国北方汉族女性乳腺癌易感性及其他临床病理特征之间无明显相关性。     

Allelic imbalance at rs6983267 suggests selection of the risk allele in somatic colorectal tumor evolution

A common single nucleotide polymorphism (SNP), rs6983267, at 8q24.21 has recently been shown to associate with colorectal cancer (CRC). Three independent SNP association studies showed that rs6983267 contributes to CRC with odds ratios (OR) of 1.17 to 1.22. Here, we genotyped a population-based series of 1,042 patients with CRC and 1,012 healthy controls for rs6983267 and determined the contribution of SNP to CRC in Finland, using germ line DNA, as well as the respective cancer DNA in heterozygous patients. The comprehensive clinical data available from the 1,042 patients and their first-degree relatives enabled us to thoroughly examine the possible association of this variant with different clinical features. As expected, a significant association between the G allele of rs6983267 and CRC [OR, 1.22; 95% confidence interval (CI), 1.08-1.38; P = 0.0018] was found, confirming the previous observations. A trend towards association of the G allele with microsatellite-stable cancer (OR, 1.37; 95% CI, 1.02-1.85; P = 0.04) and family history of cancers other than CRC was seen (OR, 1.20; 95% CI, 1-1.43; P = 0.05). Four hundred and sixty-six GT heterozygotes identified in this study were analyzed for allelic imbalance at rs6983267 in the respective cancer DNA. One hundred and one tumors showed allelic imbalance (22%). The risk allele G was favored in 67 versus 34 tumors (P = 0.0007). This finding implicates that the underlying germ line genetic defect in 8q24.21 is a target in the somatic evolution of CRC.     

Pathway-Affecting Single Nucleotide Polymorphisms (SNPs) in RPS6KA1 and MBIP Genes are Associated with Breast Cancer Risk

Background: Genetic mutations and polymorphisms play an important role in the transformation of primary cells to malignant cells as it may lead to disturbance of vital pathways regulating cell cycle, DNA damage repair, and apoptosis. In this study, we genotyped single nucleotide polymorphisms (SNPs) which were predicted to affect certain pathways and to increase the risk of breast cancer. Methods: The study included 81 Saudi breast cancer patients and 100 matching healthy controls from the Eastern Province in Saudi Arabia. The following SNPs (rs3168891, rs2899849, rs2230394, rs2229714) were then genotyped by TaqMan genotyping assay and the allele and genotype distribution was compared. Results: The minor allele frequency of the following SNPs (rs3168891, rs2899849, rs2230394, rs2229714) was T=0.17, A=0.28, A=0.22, and G=0.16 respectively. The G allele of the SNP rs3168891 was significantly associated with increased breast cancer risk (P = 0.00001) while the T allele of the same locus was associated with reduced risk of breast cancer in both heterozygous and homozygous states. The T allele of SNP rs2229714 which is located in the RPS6KA1 gene was also significantly associated with the increased risk of breast cancer. However, the rs2899849 SNP located in the Integrin beta-1 (ITGB1) gene was not associated with the increased risk of breast cancer in our study population. Haplotype analysis revealed the presence of three risk haplotypes that increases the risk of breast cancer (TGGT, TGTA, GATA). Conclusion: We showed that three, previously untested, SNPs are associated with increased risk of breast cancer in our population.  This may be added to the list of factors involved in breast cancer risk assessment studies. The benefit and the utility of the in-silico prediction of disease risk factors and their genetic association had been demonstrated in this study, yet the predicted risk alleles have to be tested in clinical studies.     

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 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.     

Genetic variants in SLC22A3 contribute to the susceptibility to colorectal cancer

Previous a genome-wide association study (GWAS) of colorectal cancer in Japanese population has identified a risk region at the chromosome 6q26-q27 associated with colorectal cancer risk. However, the causal gene at this locus remained unclear. In our study, we enrolled a total of 14 candidate functional single nucleotide polymorphisms (SNPs) at 6q26-q27 (318 kb), and then genotyped them by TaqMan method in a Chinese population including 1,147 colorectal cancer cases and 1,203 controls. Among that, 5 SNPs were identified statistical association with colorectal cancer risk by logistic regression analysis. Of which, SNP rs420038 G > A in SLC22A3 was related to decreased risk of colorectal cancer (adjusted odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.67–0.94, p = 0.007), and also associated with lower expression of SLC22A3 (p = 0.040) using expression quantitative trait loci (eQTL) analysis. Moreover, by the luciferase assays, we found that compared to the G allele of rs420038, the A allele could suppress the activity of the promoter in SLC22A3. Furthermore, the expression of SLC22A3 was significantly higher in colorectal cancer tissues than that in paired normal tissues (p < 0.001). Meanwhile, the phenotypes of proliferation, migration, invasion, cell cycle and apoptosis of colorectal cancer cell were significantly affected by SLC22A3 in vitro. Our results revealed a novel susceptible locus, rs420038 in SLC22A3, which may be involved in colorectal cancer development and progression.     

lncRNA MEG3 基因多态性与不同宫颈病变的相关性研究

目的:探讨MEG3 rs10132552 和rs7158663单核苷酸多态性（single nucleotide polymorphism，SNP）与不同宫颈病变患者发病风险的关系。方法:2018年11月到2020年11月，收集328例宫颈病变患者的外周静脉血及相关临床信息为病例，包括210例宫颈上皮内病变（cervical intraepithelial neoplasia，CIN）患者和118例宫颈癌（cervical cancer,CC）患者，以同期住院的345例无宫颈病变患者作为对照组，采用TaqMan RT-PCR方法进行基因分型，采用χ2检验和logistic 回归分析SNP位点与不同级别宫颈病变的相关性。结果:与对照组相比，MEG3 rs10132552 CT+CC基因型在宫颈病变组中分布频率显著降低（P＜0.05），其发病风险为0.701（95%CI:0.515~0.954）；且在>50岁患者中，携带MEG3 rs10132552 CT+CC基因型发生宫颈病变的风险显著降低(OR=0.634，95%CI:0.412~0.978,P＜0.05)。将宫颈病变组分为宫颈上皮内病变组和宫颈癌组进行分层分析发现，该位点CT+CC基因型主要降低了宫颈癌组的发病风险（OR=0.520，95%CI:0.333~0.811，P＜0.05)；进一步进行临床进展相关性分析，未发现MEG3 rs10132552与不同级别宫颈上皮内病变、不同病理类型、临床分期的宫颈癌具有相关性(P＞0.05)。未发现MEG3 rs7158663位点与不同级别宫颈病变具有相关性(P＞0.05)。结论:MEG3 rs10132552 SNP与宫颈癌的发病风险相关，其CT+CC基因型可能是宫颈癌发生的保护因素。