叶酸代谢相关酶基因多态性与消化系统肿瘤的关系

叶酸的主要生物学功能是作为甲基供体参与脱氧核糖核酸合成和细胞内甲基化反应.亚甲基四氢叶酸还原酶(methylene tetrahydrofolate reductase,MTHFR)、甲硫氨酸合成酶(methionine synthase,MTR)、甲硫氨酸合成酶还原酶(methionine synthase reductase,MTRR)、胸苷酸合成酶(thymidylate synthase,TS)和亚甲基四氢叶酸脱氢酶(methylenetetrahydrofolate dehydrogenase,MTHFD)等是叶酸代谢通路中重要的酶.叶酸代谢相关酶基因变异、叶酸缺乏或代谢障碍与肿瘤的发生和发展有关.本文就叶酸代谢相关酶基因多态性与消化系统肿瘤间的关系进行简要综述.     

DNA修复基因多态性影响晚期胃癌卡培他滨联合奥沙利铂化疗的临床预后

目的:探讨DNA修复基因(ERCC1、ERCC2、XRCC1)单核苷酸多态性对胃癌患者卡培他滨联合奥沙利铂化疗敏感性的相关性.方法:本回顾性研究选取XELOX作为一线化疗方案的100例晚期胃癌患者为研究对象,检测分析三个基因六个单核苷酸多态性位点(ERCC1 rs11615;ERCC2 rs13181,rs1799793;XRCC1 rs25487,rs25489,rs1799782),同时分析其与临床预后的关系.结果:XRCC1 rs25487的A/G等位基因频率、AG/AA/GG基因分布频率均与疾病化疗敏感性和无进展生存期有关,携带GG基因型患者疗效好(P<0.05),中位PFS为8.00个月(95%CI:6.34~9.66);ERCC2 rs13181的G/T等位基因频率、GG/GT/TT基因分布频率与疾病化疗敏感性和无进展生存期明显相关,携带TT基因型患者疗效好(P<0.05),中位PFS为7.46个月(95%CI:6.45~8.48).COX比例风险模型显示ERCC2 rs13181 G/T基因型是晚期胃癌无进展生存期的独立风险因素之一(HR=0.72,95%CI:0.53~0.97,P=0.025).结论:ERCC2 rs13181基因多态性可能是评估接受XELOX化疗晚期胃癌患者预后的关键指标.     

MTHFR多态性对晚期胃癌患者化疗作用的预测研究

目的:研究亚甲基四氢叶酸还原酶(MTHFR)基因C677T、A1298C多态与胃癌患者对5-FU为基础的化疗敏感性和毒性的关系。方法:晚期胃癌患者106例,用聚合酶链反应-限定性片段长度多态性(PCR-RFLP)技术检测白细胞DNAMTH-FR基因型。所有患者经5-FU为基础的化疗方案治疗。结果:1)在106例晚期胃癌患者中,MTHFRC677TCC、CT、TT基因型分别占31·1%、46·2%和22·6%;MTH-FRA1298CAA、AC、CC基因型者分别为69·8%、29·2%和0·9%;化疗总有效率35·8%。2)MTHFRC677TTT基因型携带者化疗有效率(83·3%)明显高于C677TCT(24·5%;P=0·000)和C677TCC(18·2%;P=0·000)。而MTHFRA1298CAA组有效率(43·2%)亦明显高于A1298CAC CC组(18·8%,P=0·009)。3)在CFL、CFH、LFP方案治疗的患者中,C677T变异子携带者对化疗敏感性更高。对A1298C多态性,患者接受CFL方案化疗时,1298AA纯合子携带者有效率高于1298CT/CC患者。4)MTHFRC677TTT、CT或A1298CAA多态性携带者化疗相关的恶心/呕吐发生率明显高于其他三种多态性者。结论:MTHFR基因多态性的检测可能是晚期胃癌患者接受5-FU为基础化疗疗效和毒副反应的良好预测指标。     

亚甲基四氢叶酸还原酶多态性与乳腺癌化疗敏感性的相关研究

目的:观察叶酸代谢的关键酶亚甲基四氢叶酸还原酶(MTHFR)基因C677T、A1298C多态性与乳腺癌FEC方案化疗敏感性的关系。方法:收集经病理学确诊的初治乳腺癌患者104例,所有病例化疗前抽静脉血,提取DNA,用PCR-RFLP技术检测MTHFR基因型,所有患者行FEC方案新辅助或姑息性化疗2~6周期,比较疗效和基因型之间的关系。结果:104例乳腺癌患者中,MTHFR C677T T/T基因型39例(37.5%)、C/C基因型55例(52.9%)、C/T基因型 10例(9.6%);T/T基因型化疗有效率79.5%(31/39)高于C/C基因型52.7%(29/55)和C/T基因型20.0%(2/10)（P＜0.05）。MTHFR A1298C A/A基因型41例(39.4%),A/C基因型56例(53.8%),C/C基因型7例(6.7%);各基因型化疗有效率之间无统计学关系（P＞0.05）。结论:本研究初步显示MTHFR C677T基因多态性对预测乳腺癌化疗效果具有较好的临床应用价值。     

BRCA1多态性与晚期胃癌铂类化疗敏感性及预后关系

目的: 探讨乳腺癌易感基因1(breast cancer susceptibility gene1,BRCA1)单核苷酸多态性(single nucleotide polymorphism,SNP)与晚期胃癌患者化疗反应及预后的关系。方法: 对2016年05月～2020年03月苏州科技城医院肿瘤科接受奥沙利铂联合卡培他滨化疗的153例初治晚期胃癌患者进行临床疗效评价,并随访总生存期(overall survival,OS)。采用TaqMan探针法检测BRCA1基因rs8176318G/T、rs799917C/T和rs1799966T/C多态性,用χ2检验比较不同基因型间化疗疗效的差异,Kaplan-Meier法进行生存分析,组间比较用Log-rank检验,Cox比例风险模型评估各种因素对生存预后的影响。结果: rs8176318G/T多态性与晚期胃癌化疗敏感性相关,随着T等位基因数目的增加,化疗有效率明显升高(GG24.44%、GT44.28%、TT50.00%),GT基因型化疗有效率为GG基因型的2.46倍(95%CI：1.074~5.620,χ2=4.534,P=0.033);TT基因型化疗有效率为GG基因型的3.09倍(95%CI：1.218~7.841,χ2=5.645,P=0.018);GT+TT基因型化疗有效率为GG基因型的2.67倍 (95%CI：1.224~5.801,χ2=6.096,P=0.014)。Kaplan-Meier法及Log-rank检验显示,rs1799966T/C多态性与患者生存预后相关,随着C等位基因的增加,OS显著延长,TT、TC和CC基因型患者中位OS分别为9.50、11.80、16.00个月(χ2=12.719,P=0.002), TC+CC基因型患者中位OS为13.90个月,与TT组比较差异有统计学意义(χ2=7.480,P=0.006)。多因素分析结果显示,rs1799966T/C多态性仍是影响患者OS的独立预后因素。未发现rs799917C/T多态性与化疗反应及预后之间存在统计学关联。结论: BRCA1基因rs8176318G/T多态性与晚期胃癌患者化疗敏感性相关,rs1799966T/C多态性可能影响患者生存预后。     

亚甲基四氢叶酸还原酶基因多态性检测在肿瘤患者中的临床价值

摘 要：亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase MTHFR)是叶酸代谢、DNA甲基化的关键酶。MTHFR的单核苷酸多态性(single nucleotide polymorphism,SNP),包括677 C→T和1298A→C突变,可使MTHFR酶活性下降,从而影响细胞内叶酸的正常代谢。全文分析MTHFR 基因多态性对叶酸代谢和DNA合成的影响及其在恶性肿瘤发生、诊治和预后的研究进展,阐述恶性肿瘤患者中检测MTHFR基因多态性的价值及存在争议。     

MTHFR 677C/T基因多态性与培美曲塞对晚期肺腺癌患者疗效的关系

目的 探索亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)677C/T基因多态性在预测培美曲塞治疗晚期肺腺癌疗效中的作用.方法 39例初治晚期肺腺癌患者入组并行培美曲塞/顺铂方案化疗,37例患者按要求完成治疗并进行随访.通过Taqman MGB探针实时荧光定量PCR方法检测患者MTHFR677 C/T位点的基因多态性,分析基因多态性与化疗客观缓解率(response rate,RR)和无进展生存时间(progressionfree survival,PFS)的关系.结果 MTHFR 677C/T基因频率:CC 40.5％ (15/37),CT 43.2％(16/37),TT16.2％ (6/37),MTHFR CC、CT和TT基因型客观缓解率之间差异无统计学意义(26.7％ vs 31.3％vs50.0％,P=0.582).CC基因型与CT或TT基因型之间PFS差异无统计学意义(4.7月vs 6.9月,P=0.499).结论 MTHFR 677C/T多态性可能与晚期肺腺癌培美曲塞化疗疗效无相关性.     

BRCA1多态性与晚期胃癌铂类化疗敏感性及预后关系

目的: 探讨乳腺癌易感基因1(breast cancer susceptibility gene1,BRCA1)单核苷酸多态性(single nucleotide polymorphism,SNP)与晚期胃癌患者化疗反应及预后的关系。方法: 对2016年05月～2020年03月苏州科技城医院肿瘤科接受奥沙利铂联合卡培他滨化疗的153例初治晚期胃癌患者进行临床疗效评价,并随访总生存期(overall survival,OS)。采用TaqMan探针法检测BRCA1基因rs8176318G/T、rs799917C/T和rs1799966T/C多态性,用χ2检验比较不同基因型间化疗疗效的差异,Kaplan-Meier法进行生存分析,组间比较用Log-rank检验,Cox比例风险模型评估各种因素对生存预后的影响。结果: rs8176318G/T多态性与晚期胃癌化疗敏感性相关,随着T等位基因数目的增加,化疗有效率明显升高(GG24.44%、GT44.28%、TT50.00%),GT基因型化疗有效率为GG基因型的2.46倍(95%CI：1.074~5.620,χ2=4.534,P=0.033);TT基因型化疗有效率为GG基因型的3.09倍(95%CI：1.218~7.841,χ2=5.645,P=0.018);GT+TT基因型化疗有效率为GG基因型的2.67倍 (95%CI：1.224~5.801,χ2=6.096,P=0.014)。Kaplan-Meier法及Log-rank检验显示,rs1799966T/C多态性与患者生存预后相关,随着C等位基因的增加,OS显著延长,TT、TC和CC基因型患者中位OS分别为9.50、11.80、16.00个月(χ2=12.719,P=0.002), TC+CC基因型患者中位OS为13.90个月,与TT组比较差异有统计学意义(χ2=7.480,P=0.006)。多因素分析结果显示,rs1799966T/C多态性仍是影响患者OS的独立预后因素。未发现rs799917C/T多态性与化疗反应及预后之间存在统计学关联。结论: BRCA1基因rs8176318G/T多态性与晚期胃癌患者化疗敏感性相关,rs1799966T/C多态性可能影响患者生存预后。     

MTHFR和ABCG2单核苷酸多态性对晚期结直肠癌—线化疗疗效的预测作用

目的:探讨亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)和乳腺癌耐药蛋白(breast cancer resistance protein,BCRP/ABCG2)基因单核苷酸多态性(single nucleotide polymorphism,SNP)对晚期结直肠癌一线化疗疗效的预测作用.方法:采用基因测序法检测154例接受FOLFOX、XELOX或FOLFIRI方案一线化疗的晚期结直肠癌患者外周血MTHFR 677C＞T、MTHFR 1298A＞C、ABCG2 34G＞A和ABCG2 421C＞A这4个位点的SNP,结合临床特征,分析其与近期疗效、无进展生存(progression-free survival,PFS)和总生存(overall survival,OS)之间的关系.结果:154例患者接受一线化疗的有效率为31.8％,中位PFS为8.1个月,中位OS为30.7个月.MTHFR和ABCG2 SNP与近期疗效和OS无显著相关性(P＞0.05).含3～4个优势基因型(MTHFR 677C/C、MTHFR 1298A/A、ABCG2 34G/A或A/A及ABCG2 421C/A或A/A)患者的中位PFS较含0～2个优势基因型患者的显著延长(分别为9.8和7.5个月,P=0.013).COX多因素分析结果显示,优势基因型数目(P=0.017)和原发灶是否根治切除(P=0.010)是影响PFS的独立因素.单因素和多因素分析结果均显示,原发灶是否根治切除是影响OS的独立因素(P=0.000,P=0.000).结论:联合分析MTHFR和ABCG2 SNP对一线化疗治疗晚期结直肠癌的PFS有一定的预测作用,原发灶是否根治切除是影响PFS和OS的独立因素.     

亚甲基四氢叶酸还原酶基因多态性与结直肠癌易感性的关系

目的:研究亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)基因C677T、A1298C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371例),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MTHFR C677T、A1298C基因型。结果:1)男女合计的结直肠癌组、结肠癌组和直肠癌组与对照组之间的MTHFR C677T、A1298C基因型分布频度和等位基因频度差异无统计学意义,MTHFR C677T、A1298C基因多态与结直肠癌、结肠癌和直肠癌的易感性无显著相关。2)在男性中,结肠癌组MTHFR C677T T/T基因型的频度为24.6%,明显高于对照组的14.8%,但差异无统计学意义,χ2=3.42,P=0.064。与C677T C等位基因携带者相比,T/T基因型者发生结肠癌的危险性显著升高,其性别、年龄、居住地区及吸烟、饮酒和饮茶习惯调整后的OR为2.15(95%CI:1.07~4.33)。与同时携带MTHFR C677T C等位基因和A1298C A/A基因型者相比,男性的MTHFR C677T T/T和A1298C A/A基因型携带者发生结肠癌的危险性显著升高,其调整OR为2.64(95%CI:1.20~5.81),而他们发生直肠癌的危险性则明显降低,(调整OR=0.47,95%CI:0.22~1.03)。结论:MTHFR C677T基因多态可以影响男性结、直肠癌的易感性,MTHFR A1298C多态与C677T多态在对男性结、直肠癌易感性的影响中有协同作用。     

Association of Two CD44 Polymorphisms with Clinical Outcomes of Gastric Cancer Patients

Objective: CD44 is an important cell adhesion molecule that plays a key role in growth, invasion, proliferation andmetastasis of cancer cells. CD44 protein over-expression is associated with a poor prognosis of gastric cancer (GC) andprevious studies have shown that CD44 gene polymorphisms could affect survival and recurrence. In this study, wetested the hypothesis that polymorphisms impacting on the CD44 signaling pathway may predict clinical outcomes inpatients with GC. Materials and Methods: DNA was extracted from blood of 150 healthy individuals and formalin-fixedparaffin-embedded (FFPE) tumor tissue of 150 patients. The two polymorphisms rs187116 and rs7116432 werestudied by RFLP-PCR and sequencing techniques. Results: There was a strong significant correlation between singlenucleotide polymorphisms (SNPs) in the CD44 gene, tumor recurrence, and overall survival (p <0.0001). The existenceof a significant relationship between tumor recurrence and overall survival was proved in this study, with at least oneallele G for the polymorphism rs187116 and at least one allele A for polymorphism rs7116432. Conclusion: These resultsprovide evidence of a relationship between CD44 gene polymorphisms and clinical outcomes in our GC patients.This result could help identify individuals with GC who have a high risk of tumor recurrence.     

SNP芯片联合质谱筛检胃癌相关基因3'UTR区SNPs的病例-对照研究

目的：探讨胃癌发生相关基因3'非翻译区（3'UTR）单核苷酸多态性位点（SNPs），为寻找有价值的胃癌分子标志物提供新的依据。方法：采用1：1配对病例-对照研究的方法。应用SNP芯片对福建省胃癌高发区96例胃腺癌患者与96例健康对照人群基因组中消化道肿瘤相关基因3'UTR区SNPs位点进行检测，应用飞行时间质谱分析质谱技术对芯片筛检出来的SNPs位点在622例胃癌患者和622例正常健康基因组中进行验证。结果：SNP芯片及生物信息学分析选取EGFR rs884225、EGFR rs10277413、FAS rs1468063、MSH2 rs17502941和MSH2 rs11125144为候选基因位点。对622对病例-对照组样本的上述候选基因位点进行SNP分型，均未发现上述5个位点与胃癌易感性相关。进一步分层分析结果发现EGFR rs884225中含有T等位基因的基因型（CT+TT）与贲门癌相关（OR=0.67，95% CI：0.46~0.99），而其他位点与贲门癌、非贲门癌的风险关联无统计学意义（P > 0.05）。结论：EGFR基因3'非翻译区的rs884225多态性位点与福建省仙游县的贲门癌发生存在关联，T等位基因可能是贲门癌发生的一个遗传保护因素。     

Association of variants in genes encoding for macrophage-related functions with clinical outcome in patients with locoregional gastric cancer

We provide the first evidence demonstrating that single-nucleotide polymorphisms in macrophage function-related genes may predict prognosis in locoregional gastric cancer patients. Our results also suggest that the immune-related component of tumor for progression may be dictated not only by the malignant epithelial component but also by the genetic predisposition of host in gastric cancer.BackgroundNuclear factor-kappaB (NF-κB) and CCL2/CCR2 chemokine axis play a central role in tumor progression such as stimulation of angiogenesis, acceleration of tumor invasion and migration, and suppression of innate immunosurveillance in the macrophage-related functions. There have been few reports regarding association of the macrophage function-related genes with the clinical outcome in gastric cancer. We hypothesized that variants in genes encoding for NF-κB and CCL2/CCR2 axis may predict prognosis in gastric cancer and tested whether the functional single-nucleotide polymorphisms (SNPs) will be associated with clinical outcome in patients with gastric cancer across two independent groups.Patients and methodsThis study enrolled two cohorts which consisted of 160 Japanese patients and 104 US patients with locoregional gastric cancer. Genomic DNA was analyzed for association of 11 SNPs in NFKB1, RELA, CCL2, and CCR2 with clinical outcome using PCR-based direct DNA sequencing.ResultsThe univariable analysis showed four SNPs had significant association with clinical outcome in the Japanese cohort, NFKB1 rs230510 remained significant upon multivariable analysis. The patients with the A allele of the NFKB1 rs230510 had significantly longer overall survival (OS) compared with those with the T/T genotype in both the Japanese and US cohort in the univariable analysis. In contrast, genotypes with the T allele of CCL2 rs4586 were significantly associated with shorter OS compared with the C/C genotype in the US cohort [hazard ratio (HR) 2.43; P = 0.015] but longer OS in the Japanese cohort (HR 0.58; P = 0.021), resulting in the statistically significant opposite impact on OS (P = 0.001).ConclusionsOur study provides the first evidence that the NFKB1 rs230510 and CCL2 rs4586 are significantly associated with the clinical outcome in patients with locoregional gastric cancer. These results also suggest that the genetic predisposition of the host may dictate the immune-related component of the tumor for progression in gastric cancer.     

胃癌差异表达miRNA及其相关基因的单核苷酸多态性与胃癌预后的相关性研究

目的：探讨胃癌差异表达微小RNA（miRNA）及其相关基因的单核苷酸多态性（SNPs）与胃癌预后的相关性，为进一步寻找胃癌预后的生物标志物提供线索。方法：应用SNP芯片联合生物信息学分析对福建省胃癌高发区仙游县96例胃腺癌患者与96例健康对照人群基因组中miRNA及其相关基因的SNPs位点进行筛检，应用飞行时间质谱生物芯片（Sequenom MassARRAY）在344例胃癌患者中对筛检出来的SNPs位点进行检测。开展现场流行病学调查，通过面对面的访谈及问卷调查取得患者的病情、治疗方法、患病后1年的生活饮食习惯，分析其预后情况。结果：共筛检出11个miRNA及其相关基因的SNPs位点，包括5个miRNA自身SNPs、5个miRNA靶序列SNPs以及1个miRNA生物合成通路基因相关SNPs。单因素分析显示miR-1297 rs9536676、MSH2 rs17502941位点的多态性与胃癌预后有关联性，其余的多态性位点均与胃癌预后无明显相关性。多因素分析显示是否手术、TNM分期、rs17502941 AA/AG基因型均是影响胃癌预后的独立危险因素。按年龄TNM分期联合分层得出，miR-1297 rs9536676、miRNA-519b rs10413288、miR-379 rs7143252、FAS基因rs1468063、EGFR基因rs10277413位点均与胃癌患者的生存分布有关联。联合作用分析结果显示患者同时携带rs9536676 AA/AG和rs17502941 GG、rs9536676 AA/AG和rs10413288 AA、rs17502941 GG和rs10413288 AA基因型可能会增加预后不良的风险（P < 0.05）。结论：胃癌差异表达miRNA及其相关基因的SNPs与胃癌病人预后密切相关，可能作为判断胃癌预后的生物标志物。     

胃癌差异表达miRNA及其相关基因的单核苷酸多态性与胃癌预后的相关性研究

目的：探讨胃癌差异表达微小RNA（miRNA）及其相关基因的单核苷酸多态性（SNPs）与胃癌预后的相关性，为进一步寻找胃癌预后的生物标志物提供线索。方法：应用SNP芯片联合生物信息学分析对福建省胃癌高发区仙游县96例胃腺癌患者与96例健康对照人群基因组中miRNA及其相关基因的SNPs位点进行筛检，应用飞行时间质谱生物芯片（Sequenom MassARRAY）在344例胃癌患者中对筛检出来的SNPs位点进行检测。开展现场流行病学调查，通过面对面的访谈及问卷调查取得患者的病情、治疗方法、患病后1年的生活饮食习惯，分析其预后情况。结果：共筛检出11个miRNA及其相关基因的SNPs位点，包括5个miRNA自身SNPs、5个miRNA靶序列SNPs以及1个miRNA生物合成通路基因相关SNPs。单因素分析显示miR-1297 rs9536676、MSH2 rs17502941位点的多态性与胃癌预后有关联性，其余的多态性位点均与胃癌预后无明显相关性。多因素分析显示是否手术、TNM分期、rs17502941 AA/AG基因型均是影响胃癌预后的独立危险因素。按年龄TNM分期联合分层得出，miR-1297 rs9536676、miRNA-519b rs10413288、miR-379 rs7143252、FAS基因rs1468063、EGFR基因rs10277413位点均与胃癌患者的生存分布有关联。联合作用分析结果显示患者同时携带rs9536676 AA/AG和rs17502941 GG、rs9536676 AA/AG和rs10413288 AA、rs17502941 GG和rs10413288 AA基因型可能会增加预后不良的风险（P < 0.05）。结论：胃癌差异表达miRNA及其相关基因的SNPs与胃癌病人预后密切相关，可能作为判断胃癌预后的生物标志物。     

福建地区汉族人群中CLDN23基因SNPs多态性与胃癌遗传易感性及预后的相关性CSCD

目的探讨福建地区汉族人群中已知的三种claudin-23基因CLDN23单核苷酸多态性(SNPs)与胃癌遗传易感性及预后的相关性。方法应用PCR-LDR法检测CLDN23基因3个SNP位点rs12153、rs1060106 和rs11249884的基因型。结果 CLDN23基因SNP位点rs12153、rs1060106及rs11249884三个位点的基因型及等位基因频率在胃癌病例组和健康者之间差异均无统计学意义(P>0.05);胃癌病例组中三个位点的基因型分布频率与肿瘤分化程度、pT分期显著相关(P<0.05);rs12153、rs1060106的基因型分布频率与患者术后生存时间显著相关(P<0.05);CLDN23基因SNP位点rs12153、rs1060106和rs11249884两两之间未见明显的遗传连锁不平衡性;rs12153、rs1060106和rs11249884可能存在的基因单体型中,C-T-G单体型在胃癌病例组与正常对照组之间有显著差异(P<0.01)。结论福建汉族人群中,CLDN23基因SNP位点rs12153、rs1060106及rs11249884的多态性与胃癌的分化、pT分期具有相关性,可能参与胃癌的进展,rs12153、rs1060106的多态性与胃癌患者的预后有关。     

Analysis of the association of interleukin-17 gene polymorphisms with gastric cancer risk and interaction with Helicobacter pylori infection in a Chinese population

We aimed to explore the association between interleukin-17 (IL-17) polymorphisms, Helicobacter pylori infection, and subsites in gastric cancer risk in a Chinese population. We genotyped three promoter polymorphisms (rs2275913G>A, rs3748067C>T, and rs763780T>C) of IL-17 in a case–control study of 260 gastric cancer patients and 512 healthy controls. An unconditional multiple logistical regression model was used to calculate the effects of IL-17 gene polymorphisms on gastric cancer risk. The rs2275913 AA (adjusted OR?=?1.69, 95 % CI?=?1.15–2.49) and rs3748067 TT (adjusted OR?=?1.73, 95 % CI?=?1.03–2.94) genotypes were associated with an increased risk of gastric cancer. We observed a significant interaction among rs2275913G>A, rs3748067C>T, and H. pylori infection on the risk of gastric cancer (p for interaction of 0.036 and 0.048, respectively). H. pylori infection subjects carrying the rs2275913 AA (adjusted OR?=?2.48, 95 % CI?=?1.49–4.12) and rs3748067 TT (adjusted OR?=?2.54, 95 % CI?=?1.34–5.12) genotypes had a greatly increased risk of gastric cancer compared to negative H. pylori participants. Similarly, subjects carrying the rs2275913 AA (adjusted OR?=?2.09, 95 % CI?=?1.25–3.45) and rs3748067 TT (adjusted OR?=?2.29, 95 % CI?=?1.20–4.20) genotypes had a moderately increased risk of noncardia gastric cancer. A significant interaction was observed between the rs2275913G>A and rs3748067C>T genotype and subsites of gastric cancer (p for interaction of 0.044 and 0.008, respectively). The rs2275913G>A and rs763780T>C polymorphisms increase gastric cancer risk, and interact with H. pylori infection and subsites. These findings could be helpful in identifying individuals at increased risk for developing gastric cancer.     

三维适形放疗同步卡培他滨化疗治疗老年胃癌

目的:研究三维适形放疗同步卡培他滨化疗治疗老年胃癌患者的疗效、生存时间和不良反应。方法:本院收治的45例老年胃癌患者随机分为卡培他滨单药化疗组（21例）和三维适形放疗同步卡培他滨化疗组（24例）。PTV剂量1.8Gy/(25f·5w),放疗开始同步卡培他滨化疗。比较两组患者的疗效、生存时间和不良反应。结果:卡培他滨单药化疗组客观缓解率61.9%,三维适形放疗同步卡培他滨化疗组客观缓解率87.5%,有显著统计学差异(P＜0.05)。两组不良反应、生活质量无显著差异。卡培他滨单药化疗组2年生存率23.8%,三维适形放疗同步卡培他滨化疗组2年生存率50.0%,有显著统计学差异(P＜0.05)。结论:三维适形放疗同步卡培他滨化疗治疗老年胃癌可以有效提高患者的治疗效果,改善预后,不良反应可以耐受,是一种安全有效的治疗方案。     

Prostaglandin synthase 2/cyclooxygenase 2 (PTGS2/COX2) 8473T>C polymorphism associated with prognosis for patients with colorectal cancer treated with capecitabine and oxaliplatin

Purpose  The present study analyzed the polymorphisms of apoptosis-related genes and their impact on the response to chemotherapy and survival of patients with colorectal cancer. Patients and methods  A total of 76 patients with recurrent or metastatic colorectal cancer treated with capecitabine and oxaliplatin (XELOX) combination chemotherapy were enrolled in the present study. The single nucleotide polymorphisms of 15 apoptosis-related genes (TP53, BCL2L, TNFRSF10B, AKT1, PTGS2/COX2, BID, RIPK1, FAS, FASL, caspase 3, and caspase 6-10) were determined using a PCR-RFLP assay. Results  No significant association between the polymorphisms and the response was found for any of the genes analyzed. However, the T/T genotype of PTGS2 8473T>C (rs5275) was significantly correlated with a better progression-free survival (PFS) and overall survival (OS) when compared to the combined T/C and C/C genotype (Hazard ratio [HR] = 0.47; P value = 0.046 and HR = 0.16; P = 0.013, respectively) in a multivariate analysis adjusted for age, sex, performance status, disease status and curative resection. No association was noted between the other polymorphisms and survival. Conclusion  The PTGS2 8473T>C polymorphism was found to be correlated with PFS and OS in patients with advanced colorectal cancer treated with XELOX chemotherapy.     

E-selectin rs5361 and FCGR2A rs1801274 variants were associated with increased risk of gastric cancer in a Chinese population

Host immune responses are critical steps for carcinogenesis. Single nucleotide polymorphisms (SNPs) in immunoregulatory genes may influence gastric cancer risk. We performed a genotyping analysis for immunoregulatory genes in 311 gastric cancer cases and 425 controls from a Chinese population. We found that there were significant differences of E‐selectin variant rs5361 (A>C) and FCGR2A variant rs1801274 (T>C) between cases and controls (P = 0.022 and P = 0.0001, respectively). Logistic regression analysis indicated that genotype of E‐selectin rs5361AC increased the risk of gastric cancer significantly (P = 0.026, adjusted Odds ratio (OR) = 2.84, 95% confidence interval (CI) = 1.13–7.12). C allele of E‐selectin rs5361 showed a significant increased frequency in cases (P = 0.023). However, the E‐selectin variant did not affect the protein expression. E‐selectin protein was observed not only in tumor interstitial vascular endothelial cells, but also in gastric cancer cells at primary and metastatic sites. The protein was associated with clinicopathological characteristics of gastric cancer, such as age (P = 0.008), tumor size (P = 0.027), differentiation (P = 0.000), and tumor‐node‐metastasis (TNM) stage (P = 0.006). CT and CC + CT genotypes of FCGR2A variant rs1801274 increased gastric cancer risk (P = 0.000, adjusted OR = 1.92, 95%CI = 1.36–2.72; P = 0.003, adjusted OR = 1.68, 95%CI = 1.20–2.35, respectively). Interleukin‐4 receptor (IL‐4R) variant rs2107356 presented negative correlations to E‐selectin variant rs5361 and FCGR2A variant rs1801274 (P = 0.035 and P = 0.023) in conferring susceptibility to gastric cancer. We concluded E‐selectin variant rs5361 and FCGR2A variant rs1801274 were significantly associated with gastric cancer risk. Expression of E‐selectin protein would promote progression of gastric cancer. © 2011 Wiley Periodicals, Inc.