肿瘤坏死因子-α基因G308A多态性与结直肠癌发病风险Meta分析

目的:评价肿瘤坏死因子-α基因G308A多态性位点对于结直肠癌患病风险的影响。方法:以"TNF-α-308、pol-ymorphism和colorectal cancer"作为检索词,检索2000-01-01-2011-09-01PubMed和Embase数据库中所有相关文献,提取其中数据进行统计分析,以比值比(OR)和95%可信区间(95%CI)评价该位点与结直肠癌易感性的关系。结果:最终筛选出9项关于该位点的研究,其中共包含了1 708例结直肠癌病例和1 754名对照。结果显示,A等位基因和G等位基因对于结直肠癌的患病风险差异无统计学意义,OR=1.89,95%CI为0.94～3.78;各种基因模式的对比也无阳性结果,GA对比GG,OR=1.16,95%CI为0.84～1.59,AA/GA对比GG,OR=1.26,95%CI为0.90～1.77,AA对比GA/GG,OR=1.75,95%CI为0.94～3.23。人种与对照来源进行的亚组分析中,也未发现有阳性结果。结论:肿瘤坏死因子-α基因G308A多态性可能对结直肠癌易感性无影响。建议今后应纳入更多的研究证据来明确该多态性位点与结直肠癌易感性的关系。     

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。      

基质金属蛋白酶9基因多态性与肿瘤易感性Meta分析

 目的 探讨基质金属蛋白酶9基因（MMP-9）rs3918242位点多态性与肿瘤易感性的关系。 方法 使用PubMed数据库检索2011年4月以前相关文献,按纳入标准搜索研究MMP-9 rs3918242 C/T多态性与肿瘤易感性相关的文献,采用STATA软件进行统计分析。 结果 共有4 124例肿瘤患者和4 728名对照个体被纳入当前荟萃分析。分析表明MMP-9 rs3918242 C/T多态性与整个肿瘤易感性无显著相关（等位基因比 P = 0.378, OR= 0.94, 95% CI：0.83～1.07）,但在肿瘤分层分析中发现MMP-9突变型等位基因T显著降低了肺癌（P =0.026, OR=0.70,95%CI：0.51～0.96）和结直肠癌（P = 0.016, OR=0.80,95%CI：0.66～0.96）的易感性。 结论 MMP-9 rs3918242 C/T多态性与结直肠癌和肺癌易感性存在一定的相关性。     

XRCC1 Arg399Gln位点多态性和结直肠癌易感性关系的Meta分析

[目的]探讨X射线交叉互补修复基因1（X-ray repair cross-complementing group1,XRCC1）的399位点（Arg399Gln）多态性与结直肠癌（CRC）易感性的关系。[方法]检索中国生物医学数据库（CBM）、PubMed、Springer等数据库,获取有关XRCC1Arg399Gln多态性同结直肠癌易感性关系的病例对照研究并进行Meta分析,以病例组及对照组XRCC1Arg399Gln等位基因分布的比值比（OR）为效应指标,应用Meta分析软件Review Manager（version5.0.10）对各研究原始数据进行统计处理及异质性检验,计算合并OR值及其95%可信区间（95%CI）。[结果]纳入11项病例对照研究,共2287例结直肠癌患者和3485例对照,Meta分析结果显示,Gln/Gln vs.Arg/Arg OR=1.12,95%CI为0.76～1.65,Z=0.58,POR=0.56;Gln/Gln＋Arg/Gln vs.Arg/Arg OR=1.11,95%CI为0.85～1.44,Z=0.78,POR=0.43;Gln/Glnvs.Arg/Arg＋Arg/Gln OR=1.07,95%CI为0.79～1.46,Z=0.43,POR=0.67;Arg/Gln vs.Arg/Arg OR=1.14,95%CI为0.88～1.48,Z=1.02,POR=0.31。[结论]XRCC1Arg399Gln多态性与结直肠癌易感性之间无显著相关性。     

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。     

细胞周期蛋白D1基因G870A 多态性与结直肠癌易感性的系统评价

 目的 综合评价细胞周期蛋白D1(Cyclin D1) 基因G870A多态性与结直肠癌易感性的关系.方法通过CNKI、PubMed、EMCC等数据库检索文献,获得有关Cyclin D1基因G870A多态性与结直肠癌危险性关系的研究结果,并通过Meta分析进行系统评价。所有文献均采用病例对照研究或者巢式病例对照研究,以OR值为效应指标, 基因型在对照群体中的分布均符合Hardy Weinberg 遗传平衡定律,对文献进行评价筛选、异质性检验。本次Meta分析共纳入23项研究,累计病例6 344例,对照9 018例,利用RevMan5.0对各研究原始结果进行统计处理, 对突变纯合子AA 和杂合子GA 基因型与纯合基因型GG 进行比较,并计算合并OR值及其95%可信区间(CI）。结果 AA和GA与GG基因型在病例组与健康对照组之间差异有统计学意义,OR= 1.10（95%CI：1.01～1.19, P=0.02）;按不同人群进行分层分析,亚洲人群OR= 1.11（95%CI：0.98～1.26, P=0.11）,美洲人群OR= 1.13（95%CI：0.97~1.32,P=0.12),欧洲人群OR= 1.06（95%CI：0.89～1.25, P=0.52）,大洋洲人群OR= 1.05（95%CI：0.80～1.38, P=0.73）;按不同对照进行分组分析,医院基础OR= 1.07（95%CI：0.95～1.20, P=0.28）,人群基础OR= 1.13（95%CI：1.01~1.26, P=0.04）。结论 Cyclin D1基因G870A 多态性与结直肠癌易感性总体分析在统计学上具有相关性,按不同人群进行分组分析,都不支持具有相关性;按不同对照进行分组分析,以医院基础不具有相关性,以人群为基础具有相关性。     

XRCC1 R399Q基因多态性与结直肠癌易感性的Meta分析

目的探讨X—rayrepair cross—complementing group1（XRCC1）RB99Q基因多态性与结直肠癌易感性的关系。方法通过计算机检索和手工检索,收集有关XRCC1 R399Q基因多态性与结直肠癌易感性关系的文献,筛选出符合条件的文献,应用Meta分析软件对各项研究进行异质性检验,计算合并OR值及其95％可信区间,并行敏感性分析和发表偏倚的评估。结果国内外共有21篇文献纳入研究（结直肠癌组6229例;对照组10692例）。Meta分析结果显示：XRCC1 R399Q基因多态性在整个人群中与结直肠癌无明显的关联性（OR QQvs、RR=1．10,95％CI=0．90～1．35;OR QQ/RQvs.RR=1．02,95％CI=0．90～1．16;OR QQvs.RR/RQ=1．12,95％CI=0．95～1．33）。通过种族的分层分析发现XRCC1 R399Q基因多态性与结直肠癌易感性在亚洲人群和欧洲人群中无差异。结论XRCC1 R399Q基因多态性与结直肠癌间不存在明显的易感性。     

中国人群XRCC1 Arg399Gln 基因多态性与结直肠癌易感性关系的Meta分析

摘 要：［目的］探讨X线修复交叉互补基因1（X-ray repair cross complementing group 1,XRCC1）Arg399Gln基因多态性与中国人群结直肠癌易感性的关系。［方法］在PubMed、MEDLINE、EMBASE、中国知网、维普、中国生物医学文献及万方数据库中检索建库至2016年4月10日之间发表的有关XRCC1 Arg399Gln基因多态性与中国人群结直肠癌易感性关系的相关文献。按照纳入和排除标准独立选择文献、提取资料,采用Stata 12.0软件进行Meta分析,计算合并比值比（OR）及其95%可信区间（95%CI）,并进行敏感性分析和发表偏倚的估计。［结果］ 共纳入11项研究,包括3502例患者和4828例对照者。Meta分析结果显示,在Gln/Gln vs Arg/Gln遗传模型中,XRCC1 Arg399Gln基因多态性与中国人群结直肠癌发生风险有显著相关性,与基因型Arg/Gln相比,基因型Gln/Gln增加了中国人群罹患结直肠癌的风险（OR=1.23,95%CI：1.04~1.46,P=0.016）。其余遗传模型中两者间无明显相关性。［结论］ 在Gln/Gln vs Arg/Gln遗传模型中,XRCC1 Arg399Gln基因多态性与中国人群结直肠癌易感性相关,基因型Gln/Gln增加中国人群罹患结直肠癌的风险。     

生长激素1基因多态性和烟酒习惯与结直肠癌易感性的关系

目的:研究生长激素1(growth hormone1,GH1)基因T1663A多态性与结直肠癌易感性的关系。方法:在江苏省进行了一个病例-对照研究(结直肠癌患者315例,人群对照439名),调查研究对象的生活习惯,抽取静脉血,提取白细胞DNA,采用PCR-RFLP检测研究对象的GH1T1663A基因型。结果:1)GH1T/T、T/A和A/A基因型分布频度在结直肠癌组分别为42.2%、46.7%和11.1%,对照组分别为38·1%、45·9%和16·0%,两组差异无统计学意义,χ2MH=3·907,P=0·142。但在调整性别、年龄、吸烟和饮酒习惯后,A/A基因型者与T/T基因型者相比,发生结直肠癌的危险性显著降低(OR=0·88,95%CI:0·78~0·99,P=0·0287)。2)多因素分析结果显示,饮酒者患结直肠癌的危险性显著增高(OR=1·96,95%CI:1·34~2·86,P=0·0005),A/A基因型与降低结直肠癌的危险性有关,而吸烟与增加或降低结直肠癌的危险性无显著相关。3)GH1基因多态与吸烟、饮酒相互作用的分层分析发现,在不吸烟者中,GH1A/A基因型者与T等位基因型者相比,发生结直肠癌的危险性显著降低(性别和年龄调整OR=0·50,95%CI:0·27~0·93);在不饮酒者中,GH1A/A基因型者发生结直肠癌的调整OR为0·56(95%CI:0·32~0·99)。结论:T1663A GH1基因的A/A基因型可降低结直肠癌易感性,特别是在不吸烟和不饮酒者中。     

RASSF1基因SNP与陕西地区结直肠癌发病风险关系的研究

目的:探讨RASSF1基因第三外显子G133T和第六外显子A315G单核苷酸多态性(SNP)与陕西地区汉族人群结直肠癌(CRC)易感性的关系。方法:采用基于人群的病例对照研究,聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测61例CRC和122例健康对照个体RASSF1基因多态位点的基因型频率分布,比较不同基因型与CRC发生风险的关系。结果:RASSF1基因G133T多态的T等位基因频率在CRC患者组为24.6%,显著高于健康对照组的6.1%(P=0.00)。与G/G基因型相比,携带G/T基因型的个体CRC的发病风险显著增加,经性别、年龄、吸烟状况、GIC家族史校正后的OR值为2.33(95%CI=1.05-5.15)。RASSF1基因A315G多态的G等位基因频率在CRC患者组为25.4%,显著高于健康对照组的11.9%(P=0.00)。根据个体吸烟状况进行分层分析发现,与A/A基因型相比,携带A/G基因型和G等位基因(A/G+G/G基因型)可显著增加吸烟个体CRC的发病风险,经性别、年龄、GIC家族史校正后的OR值为4.5(95%CI=1.65-12.28)。根据GIC家族史进行分层分析发现,与A/A基因型相比,携带A/G基因型或G等位基因(A/G+G/G基因型)可显著增加GIC家族史阳性个体CRC的发病风险,经性别、年龄、吸烟状况校正后的OR值为3.78(95%CI=1.39-10.19)。结论:携带RASSF1基因G133T多态的T等位基因(G/T+T/T基因型)可能显著增加陕西地区人群CRC的发病风险。携带RASSF1基因A315G多态的G等位基因(A/G+G/G基因型)可能显著增加陕西地区人群CRC的发病风险。分层分析发现,G等位基因(A/G+G/G基因型)可能显著增加吸烟个体和GIC家族史阳性个体CRC的发病风险。     

Calpain-10 SNP43 and SNP19 Polymorphisms and Colorectal Cancer: a Matched Case-control Study

Objective: Insulin resistance (IR) is an established risk factor for colorectal cancer (CRC). Given thatCRC and IR physiologically overlap and the calpain-10 gene (CAPN10) is a candidate for IR, we explored theassociation between CAPN10 and CRC risk. Methods: Blood samples of 400 case-control pairs were genotyped,and the lifestyle and dietary habits of these pairs were recorded and collected. Unconditional logistic regression(LR) was used to assess the effects of CAPN10 SNP43 and SNP19, and environmental factors. Both generalizedmultifactor dimensionality reduction (GMDR) and the classification and regression tree (CART) were used to testgene-environment interactions for CRC risk. Results: The GA+AA genotype of SNP43 and the Del/Ins+Ins/Insgenotype of SNP19 were marginally related to CRC risk (GA+AA: OR = 1.35, 95% CI = 0.92-1.99; Del/Ins+Ins/Ins: OR = 1.31, 95% CI = 0.84-2.04). Notably, a high-order interaction was consistently identified by GMDRand CART analyses. In GMDR, the four-factor interaction model of SNP43, SNP19, red meat consumption, andsmoked meat consumption was the best model, with a maximum cross-validation consistency of 10/10 and testingbalance accuracy of 0.61 (P < 0.01). In LR, subjects with high red and smoked meat consumption and two riskgenotypes had a 6.17-fold CRC risk (95% CI = 2.44-15.6) relative to that of subjects with low red and smokedmeat consumption and null risk genotypes. In CART, individuals with high smoked and red meat consumption,SNP19 Del/Ins+Ins/Ins, and SNP43 GA+AA had higher CRC risk (OR = 4.56, 95%CI = 1.94-10.75) than thosewith low smoked and red meat consumption. Conclusions: Though the single loci of CAPN10 SNP43 and SNP19are not enough to significantly increase the CRC susceptibility, the combination of SNP43, SNP19, red meatconsumption, and smoked meat consumption is associated with elevated risk.     

恩施地区人群GPX1 pro200leu多态性和缺硒在儿童急性白血病中的交互作用

目的:探讨恩施人群GPX1 pro200leu多态性与儿童急性白血病关联性及其与缺硒的交互作用。方法:采用多聚酶链反应-限制性片段长度多态性(PCR-RFLP)方法分析121例儿童急性白血病患儿和129名正常对照GPX1 pro200leu基因型。非条件Logistic分析各基因型与发病中易感性关系以及与缺硒的交互作用。结果:携带L(LL/PL)基因个体患病风险较非L基因携带者(PP)风险明显增加(OR=1.44,95%CI:1.28~1.61,P=0.000;校正OR=1.53,95%CI:1.31~3.01,P=0.000);条件Logistic分析表明携带LL/PL基因型缺硒个体儿童急性白血病罹患风险是携带PP基因非缺硒的3.39倍(OR=3.39,95%CI:2.66~5.36,P=0.000)(RERI=1.83,95%CI:1.21~2.78;API=0.46,95%CI:0.28~0.76;S=1.31,95%CI:1.08~2.17)。结论:GPX1 pro200leu多态性增加恩施地区儿童急性白血病罹患风险,且与缺硒在儿童急性白血病发病中存在协同效应。     

基质金属蛋白酶1、9基因多态性与成人脑星形细胞瘤的易感性

 目的本研究旨在探索MMP-1、MMP-9基因启动子区单核苷酸多态性（Singlenucleotidepoly—morphism，SNPs）与脑星形细胞瘤易感性的关系。方法以聚合酶链反应一限制性片段长度多态性分析方法，检测236例成人星形细胞瘤及366例健康对照的MMP．1-16072G／1G及MMP-9-1562C／T多态性的基因型。结果（1）MMP-1—16072G／1GSNP等位基因型及基因型总体分布在星形细胞瘤患者组和健康对照组之间有显著性差异（P值分别为0．002和〈0．001）。与2G／2G基因型相比，1G／1G基因型可显著降低该肿瘤的发病风险（校正OR=0．58，95％CI=0．42～O．79），而2G／1G基因型对该肿瘤的易感性无显著影响（校正OR=0．74，95％CI=0．51～1．08）。根据性别、发病年龄（≤45岁或〉45岁）进行的分层分析显示了相似的结果。（2）MMP-9-1562C／T的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值分别为0．926和0．818）。与C／C基因型相比，C／T＋T／T基因型不能改变星形细胞瘤的发病风险（校正OR=1．09，95％CI：0．73～1．64）。根据性别、发病年龄、病理分级进行的分层分析，也未发现MMP-9SNP与星形细胞瘤的发病风险相关。结论MMP-1—16072G／1G多态性与星形细胞瘤的易感性有关，而MMP-9—1562C／T多态性可能不是该肿瘤的独立易感因素。     

MTHFR基因多态和饮酒习惯与结直肠癌易感相关性的研究

目的:探讨亚甲基四氢叶酸还原酶(MTHFR)与结直肠癌(CRC)风险的关系。方法:进行了以医院为基础的结直肠癌病例对照研究(结直肠癌新发病例300例,对照300例)。对叶酸代谢相关基因MTHFRC677T和A1298C多态性进行了检测,并与结直肠癌风险关联进行了分析。结果:未观察到MTH-FR677和1298多态单独对CRC发生的影响,但发现MTHFR-677CT/1298AC组合型发生结直肠癌的风险增加,OR值为2.32(95%CI,1.10～4.92,P=0.027)。未发现MTHFR单倍型和双体型基因与CRC的风险之间存在统计学的显著关联。MTHFRC677T和A1298C基因与吸烟程度之间存在交互作用(似然比检验,P=0.002,P=0.001),在吸烟<16包年者中,MTHFR-677T等位基因患结直肠癌的风险增加2.09(95%CI,1.07～4.04),而在吸烟≥16包年者中,MTHFR-1298AA基因型患结直肠癌的风险明显下降,OR值为0.37(95%CI,0.17～0.80)。MTHFRC677T多态与饮酒之间存在交互作用(似然比检验,P=0.000)。结论:MTHFR-677CT/1298AC组合型基因是CRC的危险因素,MTHFR与吸烟、饮酒之间存在一定的交互作用。     

GSTT1和GSTM1基因缺失多态与胃癌易感性

目的　探讨与致癌物解毒有关的谷胱甘肽转硫酶 (GST) T1和 M1基因遗传缺失多态与胃癌易感性的关系。方法　采用病例对照分子流行病学研究方法 ,以 PCR技术对福建省福州市 92例胃癌病例和 92例正常对照者的 GSTT1和 GSTM1基因型进行检测。结果　 GSTT1基因在胃癌病例和对照组中的缺失率分别为 5 3.3%和41.3% ,差异无显著性 (x2 =2 .6 4,P=0 .10 4)。而 GSTM1基因在胃癌病例和对照组中的缺失率分别为 6 9.6 %和5 2 .2 % ,差异具有显著性 (x2 =5 .84,P=0 .0 15 7)。携带 GSTM1(- )基因型者发生胃癌的危险性是携带 GSTM1( )基因型者的 2 .1倍 (OR=2 .10 ,95 % CI=1.10～ 4.0 1)。联合分析表明 ,GSTT1和 GSTM1基因之间可能存在联合作用 ,携带 GSTT1(- )和 GSTM1(- )基因型者发生胃癌的危险性高于携带 GSTT1( )和 GSTM1( )基因型者 (OR=4.6 7,95 % CI=1.5 5～ 14.41)。结论　 GSTM1基因缺失可能是胃癌发病的危险性因素之一     

RPSA Gene Mutants Associated with Risk of Colorectal Cancer among the Chinese Population

The primary aim of this study was to evaluate the relationship of single nucleotide polymorphisms (SNPs) inribosomal protein SA (RPSA) gene with colorectal cancer (CRC). A case-control study including 388 controls and387 patients with CRC was conducted in a Chinese population. Information about socio-demography and livingbehavior factors was collected by a structured questionnaire. Three SNPs (rs2133579, rs2269349, rs7641291)in RPSA gene were genotyped by Illumina SnapShot method. Multiple logistic regression models were used forassessing the joint effects between tea consumption and SNPs on CRC. The subjects with rs2269349 CC genotypehad a decreased risk for CRC (OR=0.60; 95%CI = 0.37-0.99), compared with TT/CT genotype after adjustmentfor covariates. A similar association of rs2269349 with rectal cancer was observed (OR=0.49; 95%CI=0.24-1.00).Further analyses indicated that this SNP could modify the protective effect of tea drinking on CRC. Amongthe subjects with rs2269349 TT/CT or rs2133579 AA/GA, there was a marginal significantly lower risk of CRC(OR and 95%CI: 0.63 and 0.39-1.01 for rs2269349; 0.64 and 0.40-1.02 for rs2133579) in tea-drinking subjects incomparison to non-tea-drinking subjects. Mutants in the RPSA gene might be associated with genetic susceptibilityto CRC and influence the protective effect of tea consumption in the Chinese population.     

Associations of Single Nucleotide Polymorphisms in miR-146a,miR-196a,miR-149 and miR-499 with Colorectal Cancer Susceptibility

Background: MicroRNAs (miRNAs) are an abundant class of endogenous small non-coding RNAs of 20-25nucleotides in length that function as negative gene regulators. MiRNAs play roles in most biological processes,as well as diverse human diseases including cancer. Recently, many studies investigated the association betweenSNPs in miR-146a rs2910164, miR-196a2 rs11614913, miR-149 rs229283, miR-499 rs3746444 and colorectalcancer (CRC), which results have been inconclusive. Methodology/Principal Findings: PubMed, EMBASE,CNKI databases were searched with the last search updated on November 5, 2013. For miR-196a2 rs11614913,a significantly decreased risk of CRC development was observed under three genetic models (dominant model:OR = 0.848, 95%CI: 0.735–0.979, P = 0.025; recessive model: OR = 0.838, 95%CI: 0.721–0.974, P = 0.021;homozygous model: OR = 0.754, 95%CI: 0.627–0.907, P = 0.003). In the subgroup analyses, miR-196a2*Tvariant was associated with a significantly decreased susceptibility of CRC (allele model: OR = 0.839, 95%CI:0.749–0.940, P = 0.000; dominant model: OR = 0.770, 95%CI: 0.653–0.980, P = 0.002; recessive model: OR =0.802, 95%CI: 0.685–0.939, P = 0.006; homozygous model: OR = 0.695, 95%CI: 0.570–0.847, P = 0.000). Asfor miR-149 rs2292832, the two genetic models (recessive model: OR = 1.199, 95% CI 1.028-1.398, P = 0.021;heterozygous model: OR = 1.226, 95% CI 1.039-1.447, P = 0.013) demonstrated increased susceptibility to CRC.On subgroup analysis, significantly increased susceptibility of CRC was found in the genetic models (recessivemodel: OR = 1.180, 95% CI 1.008-1.382, P = 0.040; heterozygous model: OR = 1.202, 95% CI 1.013-1.425, P =0.013) in the Asian group. Conclusions: These findings supported that the miR-196a2 rs11614913 and miR-149rs2292832 polymorphisms may contribute to susceptibility to CRC.     

Association between polymorphisms in UDP-glucuronosyltransferase 1A6 and 1A7 and colorectal cancer risk

Genetic polymorphisms of uridine diphosphate-glucuronosyltransferases 1A6 (UGT1A6) and 1A7 (UGT1A7) may lead to genetic instability and colorectal cancer carcinogenesis. Our objective was to measure the interaction between polymorphisms of these repair genes and tobacco smoking in colorectal cancer (CRC). A total of 68 individuals with CRC and 112 non-cancer controls were divided into non-smoker and smoker groups according to pack-years of smoking. Genetic polymorphisms of UGT1A6 and UGT1A7 were examined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We found a weak association of UGT1A6 polymorphisms with CRC risk (crude odds ratio [OR], 1.65; 95% confidence interval [95%CI], 0.9-3.1, P=0.107; adjusted OR 1.95, 95%CI 1.0-3.8, P=0.051). The ORs for the UGT1A7 polymorphisms were statistically significant (crude OR: 26.40, 95%CI: 3.5-198.4, P=0.001; adjusted OR: 21.52, 95%CI: 2.8-164.1, P=0.003). The joint effect of tobacco exposure and UGT1A6 polymorphisms was significantly associated with colorectal cancer risk in non-smokers (crude OR, 2.11; 95%CI, 0.9-5.0, P=0.092; adjusted OR 2.63, 95%CI 1.0-6.7, P=0.042). In conclusion, our findings suggest that UGT1A6 and UGT1A7 gene polymorphisms are associated with CRC risk in the Japanese population. In particular, UGT1A6 polymorphisms may strongly increase CRC risk through the formation of carcinogens not associated with smoking.