鼠双微体同源基因2遗传多态与结直肠癌患病风险的相关性

目的 探讨p53 72 Arg→Pro和鼠双微体同源基因2(MDM2) 309 T→G多态与结直肠癌(CRC)发生发展的关系.方法 采用病例-对照关联研究方法,分析1000例CRC和1300例正常对照中p53 72 Arg→Pro和MDM2 309 T→G的基因型.以多因素Logistic回归模型计算各基因型的比值比(OR)及其95%可信区间(CI).结果 携带MDM2 309 GG或TG基因型者患CRC的风险比TT基因型者显著增高,OR分别为2.06(95%CI为1.62～2.62)和1.31(95%CI为1.06～1.62).p53 72 Arg→Pro多态与CRC风险不相关.两个基因多态联合分析表明,既携带MDM2 309 GG,又携带p53 72 Pro/Pro基因型者,患CRC的OR显著高于携带MDM2 309 TT和p53 72 Pro/Pro基因型者[2.75(95%CI为1.60～4.70)比1.09(95%CI为0.63～1.88);χ2=9.83,P=0.002].结论 MDM2基因的遗传多态可能是CRC的遗传易感性因素.     

XRCC5基因多态性与高发区食管癌、贲门癌遗传易感性的相关性

背景与目的:XRCC5为DNA双链断裂修复基因,其表达异常、活性紊乱与肿瘤的发生和发展密切相关.本研究旨在探讨XRCC5基因多态性与河北省食管癌高发区一磁、涉县人群食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)和贲门腺癌(gastric cardiac adenocarcinoma,GCA)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)方法检测329例ESCC患者、255名GCA患者和631例健康对照人群XRCC5 C74468A、G74582A单核苷酸多态性(single nucleotide polymorphisms,SNP)的基因型分布.结果:XRCC5基因C74468A C和A的等位基因频率及C/C、A/C、A/A基因型频率在ESCC、GCA及对照组之间差异无显著性(P＞0.05).根据吸烟状况和上消化道肿瘤(UGIC)家族史分层分析发现,携带A等位基因(A/C A/A基因型)可能降低上消化道肿瘤阳性家族史人群的ESCC、GCA发病风险(经性别、年龄和吸烟校正后的OR分别为0.58和0.61,95%CI分别为0.38～0.90和0.38～0.97).XRCC5 G74582A基因G、A等位基因频率及鞍A/A、A/G、G/G基因型频率在ESCC、GCA及对照组之间亦差异无显著性(P＞0.05).分层分析发现,携带G等位基因(A/G G/G基因型)可能降低上消化道肿瘤阳性家族史人群的GCA发病风险(经性别、年龄和吸烟校正后的OR为0.63,95%CI为0.40～0.98).两多态性位点联合分析显示,ESCC、GCA患者与健康对照组的单体型分布差异也无显著性(P＞0.05).结论:XRCC5 C74468A A等位基因(A/C A/A基因型)可能降低磁县和涉县上消化道肿瘤阳性家族史人群的ESCC、GCA发病风险.而G74582A G等位基因(A/G G/G基因型)可能仅降低该地区上消化道肿瘤阳性家族史人群的GCA发病风险.     

XPC基因Ala499Val、Lys939Gln多态与食管癌、贲门癌发病风险的关联

背景与目的:XPC基因参与核苷酸切除修复,该基因存在单核苷酸多态性(SNP)位点,并可能通过SNP位点碱基的改变影响其修复能力及疾病易感性。本研究旨在探讨XPC基因第8外显子Ala499Val及第15外显子Lys939GlnSNP与河北省食管癌、贲门癌高发区—磁县和涉县人群食管鳞状细胞癌(esophagealsguamouscellcarcinoma,ESCC)和贲门腺癌(gastriccardiacadenocorcinoma,GCA)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)分析方法检测327例ESCC患者、253例GCA患者和612名健康对照的XPC基因第8外显子Ala499Val及第15外显子Lys939GlnSNP的基因型。结果:ESCC患者组、GCA患者组上消化道肿瘤家族史阳性个体比例明显高于对照组,上消化道肿瘤家族史可增加ESCC、GCA的发病风险(经性别和年龄校正后的OR=1.76和1.77,95%CI=1.34～2.32和1.31～2.39)。ESCC患者组和对照组的XPC基因第8外显子C、T等位基因频率及C/C、C/T、T/T基因型分布差异均无显著性(P>0.05)。GCA患者组T等位基因频率(26.5%)显著低于对照组(32.5%),两组相比差异有显著性(χ2=6.12,P=0.01);与C/C基因型相比,携带C/T基因型可显著降低GCA的发病风险(OR=0.62,95%CI=0.45～0.84)。根据吸烟状况和上消化道肿瘤家族史进行分层分析发现,与C/C基因型相比,携带C/T基因型可显著降低吸烟个体和家族史阴性个体GCA的发病风险(OR均等于0.57,95%CI=0.36～0.91和0.37～0.88)。在ESCC、GCA患者组和对照组之间,XPC第15外显子A、C等位基因频率及A/A、A/C、C/C基因型分布差异均无显著性(P>0.05)。根据吸烟状况和上消化道肿瘤家族史进行分层分析发现,与A/A基因型相比,携带C/C基因型可显著增加非吸烟个体ESCC的发病风险(OR=2.05,95%CI=1.15～3.66)。单体型分析显示,A/T、A/C、C/T、C/C四种单体型,在ESCC患者组与对照组之间分布差异无显著性(P>0.05);在GCA患者组与对照组之间分布差异有显著性(P=0.02)。与A/T单体型相比,携带A/C、C/C单体型可显著增加GCA的发病风险(OR=1.35和1.46,95%CI=1.01～1.81和1.06～2.00)。结论:在河北省食管癌、贲门癌高发区—磁县和涉县人群中,携带XPC基因第8外显子C/T基因型可能明显降低GCA的发病风险;第15外显子Lys939GlnSNP可能与ESCC、GCA的发病风险无关,但分层分析发现携带第15外显子C/C基因型可能增加非吸烟个体ESCC的发病风险;携带A/C、C/C单体型可能增加GCA的发病风险。     

RASSF1基因单核苷酸多态性与食管癌的发病风险

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食管鳞状细胞癌(ESCC)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120例ESCC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ESCC发生风险的关系.结果:RASSF1基因G133T多态的T等位基因频率和A315G多态的G等基因频率在ESCC患者组分别为17.5%和23.8%,显著高于健康对照组的6.1%和11.9%.根据个体吸烟状况进行分层分析发现,携带G/T基因型或T等位基因(G/T+T/T基因型)和携带A/G基因型或G等位基因(A/G+G/G基因型)可显著增加吸烟个体ESCC的发病风险,经性别、年龄、GIC家族史校正后的OR值分别为11.7和5.02(95%CI=3.95-34.9和2.09-12.06).GIC家族史分层分析发现,携带G/T基因型或T等位基因(G/T+T/T基因型)和A/G基因型可显著增加GIC家族史阳性个体和GIC家族史阴性个体ESCC的发病风险, 经性别、年龄、吸烟状况校正后的OR值为5.08和3.51(95%CI=1.85-13.92和1.69-7.21).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ESCC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ESCC的发病风险.     

p53codon72单核苷酸多态性与肝细胞癌发病风险的关系

[目的]探讨广西地区p53基因codon72单核苷酸多态性(SNP)与肝细胞癌(HCC)发病风险的关系。[方法]采用TaqMan MGB探针等位基因分型技术对985例肝癌病例和相匹配的992例非肿瘤对照的p53 codon72(Arg>Pro,rs1042522)基因型进行检测,并分析该SNP与肝癌发病风险的关系。[结果]p53 codon72多态性与肝癌发病风险之间无统计学关联(Arg/Pro:校正OR=1.15,95%CI:0.83～1.59;Pro/Pro:校正OR=1.16,95%CI:0.80～1.68;Arg/Pro+Pro/Pro:校正OR=1.15,95%CI:0.85～1.57)。按是否吸烟、饮酒、HBV和HCV感染分层分析,亦未发现p53 codon72多态性与肝癌发病风险有关。但基因—环境交互作用显示,该基因多态性与吸烟、饮酒和HBV感染存在交互作用,OR值分别为2.42(95%CI:1.47～3.97)、2.96(95%CI:1.82～4.80)和62.74(95%CI:34.39～114.46)。[结论]p53codon72的单独效应可能与肝癌易感性无关联,但该SNP与吸烟、饮酒和HBV感染存在基因—环境交互作用,增加肝癌的发病风险。     

XPC基因Ala499Val、Lys939Gln多态与食管癌、贲门癌发病风险的关联

背景与目的：XPC基因参与核苷酸切除修复,该基因存在单核苷酸多态性（SNP）位点,并可能通过SNP位点碱基的改变影响其修复能力及疾病易感性。本研究旨在探讨XPC基因第8外显子Ala499Val及第15外显子Lys939G1nSNP与河北省食管癌、贲门癌高发区-磁县和涉县人群食管鳞状细胞癌（esophageal sguamous cell carcinoma,ESCC）和贲门腺癌（gastric cardiac adenocorcinoma,GCA）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）分析方法检测327例ESCC患者、253例GCA患者和612名健康对照的XPC基因第8外显子Ala499Val及第15外显子Lys939Gln SNP的基因型。结果：ESCC患者组、GCA患者组上消化道肿瘤家族史阳性个体比例明显高于对照组,上消化道肘t瘤家族史可增加ESCC、GCA的发病风险（经性别和年龄校正后的OR=1．76和1．77．95％CI=1．34～2．32和1．31～2．39）.ESCC患者组和对照组的XPC基因第8外显子C、T等位基因频率及C／C、C／T、T／T基因型分布差异均无显著性（P〉0．05）。GCA患者组T等位基因频率（26．5％）显著低于对照组（32．5％）,两组相比差异有显著性（x^2=6．12,P=0．01）;与C／C基因型相比,携带C／T基因型可显著降低GCA的发病风险（OR=0．62,95％CI=0．45～0．84）。根据吸烟状况和上消化道肿瘤家族史进行分层分析发现,与C／C基因型相比,携带C／T基因型可显著降低吸烟个体和家族史阴性个体GCA的发病风险（OR均等于0．57,95％CI=0．36～0．91和0．37～0．88）。在ESCC、GCA患者组和对照组之间,XPC第15外显子A、C等位基因频率及A／A、A／C、C／C基因型分布差异均无显著性（P〉0．05）。根据吸烟状况和上消化道肿瘤家族史进行分层分析发现,与A／A基因型相比,携带C／C基因型可显著增加非吸烟个体ESCC的发病风险（OR=2．05,95％CI=1．15～3．66）。单体型分析显示,A／T、A／C、C／T、C／C四种单体型,在ESCC患者组与对照组之间分布差异无显著性（P〉0．05）;在GCA患者组与对照组之间分布差异有显著性（P=0．02）。与A／T单体型相比,携带A／C、C／C单体型可显著增加GCA的发病风险（OR=1．35和1．46,95％CI=1．01～1．81和1．06～2．00）。结论：在河北省食管癌、贲门癌高发区一磁县和涉县人群中,携带XPC基因第8外显子C／T基因型可能明显降低GCA的发病风险;第15外显子Lys939Gln SNP可能与ESCC、GCA的发病风险无关,但分层分析发现携带第15外显子C／C基因型可能增加非吸烟个体ESCC的发病风险;携带A／C、C／C单体型可能增加GCA的发病风险。     

p73及p53基因多态性与甘肃武威人群胃癌风险相关性研究

[目的]评价p73基因G4C14-to-A4T14双核苷酸多态性（p73 G4A DNP）和p53基因第72密码子单核苷酸多态性（p53 Arg72Pro SNP）与甘肃武威市人群胃癌高发风险及胃癌不同病理亚型的相关性。[方法]p73G4ADNP的基因分型采用两双相对引物多聚酶链式反应法,p53 Arg72Pro SNP基因分型采用PCR-RFLP法。[结果]共检查胃癌病例385例以及健康对照412人。胃癌组中弥漫型胃癌305例（79.22%）,肠型胃癌80例（20.78%）。对照组p73AT/AT、AT/GC及GC/GC基因型的频率分别为28.15%、47.09%和24.76%;胃癌组分别为21.98%、45.04%和32.98%;以AT/AT作为指示物,胃癌组和弥漫型胃癌的GC/GC纯合子基因型频率均高于对照组,优势比（OR）分别为1.71（95%CI,1.16～2.51）和1.87（1.24～2.81）。对照组p53基因Pro/Pro、Pro/Arg以及Arg/Arg基因型的频率分别为27.18%、50.49%及22.33%;胃癌组则分别为21.82%、45.45%和32.73%;以Pro/Pro为指示物,胃癌组和弥漫型胃癌Arg/Arg基因型频率显著高于对照组,OR分别为1.83（95%CI,1.24～2.70）和2.25（95%CI,1.47～3.43）。[结论]携带p73 G4A GC/GC基因型或p53 Arg/Arg基因型可能会增加胃癌,尤其是弥漫性胃癌的发病风险。     

MMP-12基因多态性与食管癌、贲门癌发病风险的关联

目的 本研究旨在探讨基质金属蛋白酶 12(MMP 12)基因启动子区转录起始点上游82bp处A/G单核苷酸多态性(SNP)与河北省食管癌、贲门癌高发区—磁县、涉县食管鳞状细胞癌(ESCC)和贲门腺癌(GCA)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)技术检测316名ESCC患者、243名GCA患者和609名健康对照的MMP 12 A 82G SNP的基因型。结果 MMP 12 SNP的基因型及等位基因频率在两患者组与健康对照组之间,其总体分布差异无统计学意义(P>0.05)。根据吸烟状况分层分析发现,吸烟组中GCA患者组与对照组A/A、A/G基因型频率分别是89.8%、10.2%和95.0%、5.0%,GCA患者组A/G基因型频率虽明显高于对照组,但两组相比差异无统计学意义(χ2=3.43, P=0.06),与A/A基因型相比,携带A/G基因型有增加吸烟个体GCA发病风险的趋势(OR=2.13, 95% CI=0.94～4.83)。结论 MMP 12基因A 82G SNP可能与河北省磁县和涉县人群的食管癌、贲门癌发病风险无关;但携带A/G基因型可能是吸烟人群GCA发病的危险因素。     

IL-8基因多态性与高发区食管癌发病风险的关联研究

目的: 白细胞介素-8(Interleukin-8,IL-8)属于趋化因子CXC家族的一员,是一个多细胞来源的趋化性细胞因子,介导机体的慢性炎症反应。近年来研究发现该细胞因子与肿瘤发生的关系密切,可刺激肿瘤细胞增殖,诱导肿瘤细胞移动,进而促进肿瘤的发生、发展和转移。本研究旨在探讨IL-8基因-251(A/T)位点单核苷酸多态性(Single nucleotide polymorphism,SNP)与中国太行山南麓食管癌高发区人群食管鳞状细胞癌(ESCC)发病风险的关系。 方法: 采用病例-对照研究,以聚合酶链反应-限制性片段长度多态性(PCR-RFLP)的方法,分析320例ESCC和404名健康对照者的IL-8-251A/TSNP分布情况。 结果: IL-8-251A/T基因型(AA、AT、TT)及等位基因型(A、T)在ESCC患者和健康对照组中分布总体上差异无显著性(P=0.361,P=0.969)。上消化道肿瘤(UGIC)家族史和吸烟可显著增加高发区人群ESCC的发病风险,经混杂因素校正后OR值分别为1.721(95%CI=1.251～2.367)和1.684(95%CI=1.215～2.336)。根据吸烟状况及UGIC家族史分层分析发现,在UGIC家族史阳性亚组中,与TT基因型相比,携带AA基因型明显增加ESCC的发病风险,经性别、年龄、吸烟校正后的OR值为2.378(95%CI=1.075～5.258),而其它亚组中未见IL-8-251多态性增加ESCC的发病风险。 结论: IL-8-251A/TSNP与中国太行山南麓食管癌高发区ESCC患者的发病风险无关,但携带AA基因型可增加家族聚集性ESCC的易感性。     

PLCε1基因多态性与食管癌遗传易感性的关联研究

  目的  探讨PLCε1基因rs2274223 A/G单核苷酸多态性(single nucleotide polymorphism,SNP)和rs11599672 T/G SNP与河北省磁县高发区人群食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)遗传易感性之间的关系。  方法  采用聚合酶链反应-连接酶检测反应(polymerase chain reaction-ligase detection reaction,PCR-LDR)方法对527例ESCC患者和527例健康对照PLCε1基因rs2274223 A/G SNP和rs11599672 T/G SNP进行基因分型。  结果  ESCC患者组上消化道肿瘤(upper gastrointestinal cancer,UGIC)家族史阳性个体比例为48.6%,显著高于健康对照组(39.3%,χ2=9.25,P=0.002)。ESCC患者组及健康对照组PLCε1基因rs2274223 A/G SNP AA、AG、GG基因型频率分别为48.0%、43.9%、8.1%和57.1%、37.5%、5.4%。与AA基因型相比,携带AG、GG、AG/GG基因型可能增加ESCC的发病风险,经年龄、性别、吸烟状况、UGIC家族史校正后的OR值分别为1.41(95%CI=1.09~ 1.83)、1.71(95%CI=1.03~2.86)、1.45(95%CI=1.13~1.85)。PLCε1基因rs11599672 T/G SNP等位基因频率和基因型频率总体分布在ESCC患者组及健康对照组之间无显著性差异(P>0.05)。应用2LD软件对PLCε1基因rs2274223 A/G SNP和rs11599672 T/G SNP进行联合分析显示,两个多态性位点间不存在连锁不平衡现象(D'=0.11)。与最常见的AT单体型相比,GT单体型增加了ESCC的发病风险(OR=1.36,95%CI=1.08~1.71)。  结论  PLCε1基因rs2274223 A/G SNP可以作为高发区人群ESCC遗传易感性的标志物。UGIC家族史阳性个体、携带PLCε1基因rs2274223 A/G SNP AG、GG基因型的个体罹患ESCC的风险较高,应定期接受食管内镜检查,以便真正实现ESCC的早期诊断、早期治疗。      

Genetic polymorphisms of p53 and GSTP1,but not NAT2,are associated with susceptibility to squamous-cell carcinoma of the esophagus

The interaction of genetic and environmental factors can determine an individual's susceptibility to various cancers. We present a hospital-based case-control study, which included 90 patients of esophageal squamous-cell carcinoma (ESCC) and 254 healthy people in Taiwan, to investigate the effects of genetic polymorphisms of p53, GSTP1 and NAT2 on the risk of ESCC. Polymorphisms of p53, NAT2 and GSTP1 were determined by PCR-RFLP. The codon 72 p53 Pro allele was more frequently found in ESCC patients [odds ratio (OR) 1.86, 95% confidence interval (CI) 1.04-3.35 for Arg/Pro genotype and OR 2.56, 95% CI 1.29-5.08 for Pro/Pro genotype]. In cigarette smokers, the frequency of GSTP1 Ile/Ile genotype was higher in ESCC patients (OR 2.8, 95% CI 1.4-5.7). Among alcohol drinkers, borderline significance was also found for GSTP1 Ile/Ile genotype (OR 2.0, 95% CI 0.9-4.4). Results were not similar for the NAT2 genetic polymorphism. Using logistic analyses, we found that individuals with p53 Pro/Pro genotype had a significantly higher risk of developing ESCC than those with Arg/Arg genotype (OR 2.3, 95% CI 1. 1-5.1), after adjusting for other significant environmental risk factors. This result remained similar (OR 2.2, 95% CI 1.0-4.8 for p53 Pro/Pro vs. Arg/Arg), even after further adjustment for NAT2 and GSTP1 polymorphisms. The codon 72 p53 Pro/Pro genotype in the general population and GSTP1 Ile/Ile in cigarette smokers may predict a higher risk of developing ESCC.     

Dietary selenium intake and genetic polymorphisms of the GSTP1 and p53 genes on the risk of esophageal squamous cell carcinoma.

Few studies have assessed potential effect modifications by polymorphisms of susceptibility genes on the association between selenium intake and esophageal squamous cell carcinoma (ESCC). We studied the joint effects of dietary selenium and the GSTP1 and p53 polymorphisms on ESCC risk in a population-based case-control study with 218 ESCC cases and 415 controls in Taixing City, China. Dietary selenium intake was estimated from a food frequency questionnaire with 97 food items. GSTP1 and p53 polymorphisms were detected by RFLP-PCR assays. Logistic regression analyses were done to estimate odds ratios (OR) and 95% confidence intervals (95% CI). Reduced ESCC risk was observed among individuals in the highest quartile of dietary selenium intake (adjusted OR, 0.31; 95% CI, 0.13-0.70) with a dose-dependent gradient (P(trend) = 0.01). The p53 Pro/Pro genotype was associated with increased risk of ESCC compared with the Arg/Arg genotype (adjusted OR, 2.02; 95% CI, 1.19-3.42). When combined with selenium consumption, an obvious increased risk was observed among individuals with the p53 Pro/Pro or GSTP1 Ile/Ile genotype with adjusted ORs of 3.19 (95% CI, 1.74-5.84) and 1.90 (95% CI, 1.03-3.51), respectively. Among smokers and alcohol drinkers, elevation of ESCC risk was more prominent among p53 Pro/Pro individuals who consumed a low level of dietary selenium (adjusted OR, 3.59; 95% CI, 1.49-8.66 for smokers and 6.19; 95% CI, 1.83-20.9 for drinkers). Our study suggests that the effect of dietary selenium on the risk of ESCC may be modulated by tobacco smoking, alcohol drinking, and p53 Pro/Pro and GSTP1 Ile/Ile genotypes.     

The role of P53 and MDM2 polymorphisms in the risk of esophageal squamous cell carcinoma

The tumor suppressor P53 pathway plays a crucial role in preventing carcinogenesis and genetic variations of this pathway may be associated with cancer susceptibility. We tested this hypothesis by examining the contribution of functional polymorphisms in P53 and MDM2 to risk of esophageal squamous cell carcinoma (ESCC). DNA from 758 ESCC patients and 1,420 controls were genotyped for P53 codon 72Arg>Pro and MDM2 309T>G polymorphisms. Odds ratios (OR) and 95% confidence intervals (CI) of ESCC were estimated by logistic regression. We observed an increased risk of ESCC associated with the P53 Pro/Pro (OR, 1.83; 95% CI, 1.43-2.35; P < 0.001) or MDM2 GG (OR, 1.49; 95% CI, 1.16-1.91; P = 0.002) genotype, compared with the P53 Arg/Arg or MDM2 TT genotype, respectively. Interaction between these P53 and MDM2 polymorphisms increased risk of ESCC in a multiplicative manner, with the OR being 3.10 (95% CI, 2.07-4.69) for subjects carrying both P53 Pro/Pro and MDM2 GG genotypes. Significant interactions were observed between these polymorphisms and smoking, with risk being the highest (OR, 5.29; 95% CI, 2.91-9.61) in smokers having both P53 Pro/Pro and MDM2 GG genotypes. The MDM2 GG genotype was also associated with risk of developing poorly differentiated and advanced ESCC compared with the GT or TT genotype (OR for high-grade and stages III-IV versus low-grade and stages I-II = 1.60; 95% CI, 1.00-2.64; P = 0.049). The P53 and MDM2 polymorphisms may be genetic determinants for the development of ESCC.     

P53 codon 72 polymorphism and risk of gastric cancer in a Chinese population

The p53 gene plays an important role in cell cycle control in response to DNA damage, which may increase the probability of mutations that lead to carcinogenesis. The p53 codon 72 Arg right curved arrow Pro polymorphism has been suggested to be associated with risk for different kind of cancers, but the data on gastric cancer (GC) is very limited. To evaluate the association between this polymorphism and risk of GC, we performed genotype analysis by using a polymerase chain reaction-based restriction fragment length polymorphism assay in a population-based case-control study of 324 GC patients and 317 cancer-free controls in a Chinese population. The controls were frequency-matched to the cases by age, sex and smoking status. The frequency of the p53 Arg allele was 57.4% in the cases and 54.9% in the controls, and the genotype frequencies of p53 Arg/Arg, Arg/Pro, and Pro/Pro were 29.6%, 55.6%, and 14.8%, respectively, in the cases, and 29.6%, 50.5%, and 19.9%, respectively, in the controls (p=0.207). Logistic regression analysis revealed that the p53 Arg allele (Arg/Pro and Arg/Arg genotype) was associated with a borderline significantly increased risk of gastric cancer (adjusted OR=1.44, 95% CI=0.95-2.18), particularly non-cardia gastric cancer (adjusted OR=1.67, 95% CI=1.00-2.77), compared with p53 homozygous Pro allele (Pro/Pro genotype), and the risk was significantly more evident among alcohol drinkers (adjusted OR=2.85, 95% CI=1.37-5.95). While the results suggest that the p53 codon 72 polymorphism may contribute to gastric cancer susceptibility, further larger studies are needed to substantiate our findings and to explore a possible interaction between p53 codon 72 polymorphism and alcohol in the etiology of gastric cancer.     

p21cip1和p27kip1基因遗传多态与食管癌及贲门癌发病风险的关联

背景与目的：有研究表明p21^cip1和p27^kip1的基因多态性与乳腺癌、肺癌、前列腺癌等肿瘤易感性有关。本研究分析中国北方高发区人群食管鳞状细胞癌（ESCC）和贲门腺癌（GCA）与勺p21^cip1和p27^kip1基因多态性之间的关系。方法：应用聚合酶链反应-限制性片段长度多态性（PCR—RFLP）方法检测299例ESCC患者、256例GCA患者及437名健康对照人群p21^cip1 3’非翻译区和p27^kip1第109位密码子基因多态性分布情况。结果：ESCC患者组p21^cip1 T等位基因型频率（42．8％）显著高于健康对照组（36．7％）（P=0．02）,ESCC和GCA患者组p27^kip1等位基因型频率（分别为96．8％和96．1％）均显著高于健康对照组（92．9％）（P值分别为0．00和0．02）。ESCC患者组p21^cip1基因型频率分布与健康对照组相比有显著性差异（P=0．04）,与C／C和C／T基因型相比,T／T基因型可显著增加ESCC的发病风险（校正OR=1．93,95％CI=1．12～3．94）ESCC和GCA患者细p27^kip1基因型频率分布与健康对照组相比均有显著性差异（P分别为0．00和0．01）,与V／G和G／G基因型相比,V／V基因型可显著增加ESCC和GCA的发病风险（校正OR分别为2．44和2．01,95％CI分别为1．2l～4．02和1.12～3．68）。当按吸烟和上消化道肿瘤家族史状况进行分层分析时发现,与V／G和G／G基因型相比,V／V基因型可显著增加吸烟人群患ESCC和GCA（校正OR分别为2．24和2．61,95％C1分别为1.14～4．03和1．25～3．82）以及有家族史人群患ESCC的发病风险（校正OR=2．04,95%CI=1．04～3．43）．两基因联合分析显示,携带p21^cip1T／T和p27^kip1V／V基因型可显著增加患食管癌和贲门癌的发病风险（校正OR分别为3．78和2．56,95?分别为1．46～5．89和1．06～4．78）。结论：在中国北方人群中,p21^cip1基因多态性可能与食管癌的易感性有关,p27^kip1基因多态性可能与食管癌和贲门癌的易感性有关．而且这两个基因的多念性可能存食管癌和贲门癌发病中起联合作用．     

p73基因多态性与食管癌、贲门癌遗传易感性的关系

背景与目的:p73作为一种抑癌基因,其第二外显子非编码区存在两个单核苷酸多态性(G4C14-A4T14),可以形成茎环结构而影响基因表达。本研究旨在探讨河北省食管癌高发区人群中这两个连锁多态性与食管癌、贲门癌易感性的关系。方法:采用病例-对照研究,以聚合酶链反应-限制性片段长度多态性方法,分析348例食管癌患者、259例贲门癌患者和630例健康对照者的p73基因多态性。结果:具有上消化道肿瘤家族史可明显增加食管癌和贲门癌的发病风险,经性别、年龄和吸烟状况校正的OR值分别1.68(95%CI=1.28～2.20)和1.68(95%CI=1.24～2.26)。p73G4C14-A4T14基因型及等位基因型在食管癌患者、贲门癌患者和健康对照中总体分布差异无显著性。在根据吸烟状况和上消化道肿瘤家族史进行分层分析,发现在无上消化道肿瘤家族史亚组中,携带GC/AT基因型明显增加贲门癌的发病风险(OR=1.71,95%CI=1.14～2.57),而其他亚组中未见p73G4C14-A4T14多态性增加食管癌、贲门癌的发病风险。结论:p73G4C14-A4T14多态性中,携带GC/AT基因型明显增加河北省食管癌高发区无上消化道肿瘤家族史人群贲门癌的发病风险。     

丝氨酸羟甲基转移酶基因C1420T多态性与食管鳞癌、贲门腺癌易感性的关系

背景与目的：丝氨酸羟甲基转移酶（serine hydroxymethyrltransferase,SHMT）是叶酸代谢过程中的关键酶,它通过为嘌呤、胸苷酸、蛋氨酸等重要物质的合成提供一碳单位来影响基因的甲基化和DNA的合成过程,与肿瘤的发生、发展关系密切。本研究旨在探讨河北省食管癌高发人群SHMT1 C1420T单核苷酸多态性（single nucleotide polymorphism,SNP）与食管鳞状细胞癌（esophageal squamous cell carcinoma,ESCC）和贲门腺癌（gastric cardiac adenocarcinoma,GCA）易感性的关系。方法：采用双相引物-聚合酶链反应（polymerase chain reaction-with confronting two-pair primers．PCR-CTPP）方法,检测584例ESCC患者、467例GCA患者和540名健康对照者的SHMT1 C1420TSNP的基因型．并用非条件Logistic回归模型分析多态性与食管鳞癌和贲门腺癌发病风险的关系。结果：上消化道肿瘤（upper gastrointestinal cancers,UGIC）家族史可显著增加高发区人群食管鳞癌和贲门癌的发病风险,经性别、年龄、吸烟校正后的OR值分别为2．89（95％CI=2．23～3．73）和1．68（95％CI=I．28～2．23）。ESCC组和GCA组C／T基因型频率（分别为12．0％和10．9％）明显低于健康对照组（16．5％）（P值分别〈0．05和0．01）。与C／C基因型相比,携带C／T基因型的个体ESCC、GCA的发病风险显著降低,经性别、年龄、吸烟、家族史校正后的OR值分别为0．70（95％CI=0．50～0．98）0．55（95％CI=0．38～0．81）。分层分析显示,与C／C基因型相比,C／T基因型可以显著降低非吸烟个体ESCC和GCA的发病风险,经性别、年龄、家族史校正后的OR值分别为0．54（95％CI=0．33～0．90）,0．56（95％CI=0．33～0．95）。另外,虽然C／T基因型可显著降低UGIC家族史阳性和阴性个体贲门腺癌的发病风险[校正OR值分别为0．46（95％CI=0．24～0．90）和0．62（95％CI=0．38～0．99）],该基因型仅可降低UGIC家族史阳性个体ESCC的发病风险（校正OR值为0．51,95％CI=0．29-0．89）。结论：SHMT1 C／T基因型可以显著降低中国河北省高发区ESCC、GCA的发病风险。     

P53 Arg72Pro and MDM2 SNP309 Polymorphisms Cooperate to Increase Lung Adenocarcinoma Risk in Chinese Female Non-smokers: A Case Control Study

Background: Cell cycle deregulation is a major component of carcinogenesis. The p53 tumor suppressorgene plays an important role in regulating cell cycle arrest, and mouse double minute 2 (MDM2) is a keyregulator of p53 activity and degradation. Abnormal expression of p53 and MDM2 occurs in various cancersincluding lung cancer. Methods: We investigated the distribution of the p53 Arg72Pro (rs1042522) and MDM2SNP309 (rs2279744) genotypes in patients and healthy control subjects to assess whether these single nucleotidepolymorphisms (SNPs) are associated with an increased risk of lung adenocarcinomas in Chinese female nonsmokers.Genotypes of 764 patients and 983 healthy controls were determined using the TaqMan SNP genotypingassay. Results: The p53 Pro/Pro genotype (adjusted OR = 1.55, 95% CI = 1.17–2.06) significantly correlated withan increased risk of lung adenocarcinoma, compared with the Arg/Arg genotype. An increased risk was also notedfor MDM2 GG genotype (adjusted OR = 1.68, 95% CI = 1.27–2.21) compared with the TT genotype. Combinedp53 Pro/Pro and MDM2 GG genotypes (adjusted OR = 2.66, 95% CI = 1.54–4.60) had a supermultiplicativeinteraction with respect to lung adenocarcinoma risk. We also found that cooking oil fumes, fuel smoke, andpassive smoking may increase the risk of lung adenocarcinomas in Chinese female non-smokers who carry p53or MDM2 mutant alleles. Conclusions: P53 Arg72Pro and MDM2 SNP309 polymorphisms, either alone or incombination, are associated with an increased lung adenocarcinoma risk in Chinese female non-smokers.