Interleukin-10 -1082 promoter polymorphism is not associated with susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma in a population of high-incidence region of north China

AIM: To investigate the possible association of G→A single nucleotide polymorphism (SNP) at the -1082 position of interleukin (IL)-10 promoter with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in a population of a high incidence region of North China.METHODS: IL-10-G1082A promoter SNP was genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) in 355 cancer patients (203ESCC and 152 GCA) and 443 healthy controls.RESULTS: Smoking significantly increased the risk of ESCC and GCA development (the age and sex adjusted OR = 1.42and 2.64, 95%CI = 1.11-1.81 and 1.46-4.76, respectively).Similarly, family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing ESCC and GCA (the age and sex adjusted OR = 1.44 and 3.10,95%CI = 1.18-1.75 and 1.94-4.97, respectively). The A/A, A/G and G/G genotype frequencies of IL-10-G1082A were 60.3%, 37.0% and 2.7% in healthy controls, 57.6%,39.9% and 2.5% in ESCC and 61.2%, 36.8% and 2.0% in GCA patients, respectively. The frequencies of A and G alleles were 78.8% and 21.2% in healthy controls, 77.6%and 22.4% in ESCC patients and 79.6%, 20.4% in GCA patients. The distribution of genotype and allelotype in ESCC and GCA patients was not significantly different from that in healthy controls (P＞0.05). Compared to the A/A genotype, the combination of A/G and G/G genotypes did not show a significant effect on the risk of developing ESCC and GCA; the adjusted odds ratio was 0.92 (95%CI = 0.76-1.11) in ESCC and 0.95 (95% CI = 0.61-1.46)in GCA, respectively. When stratified for smoking status and family history of UGIC, the combination of A/G and G/G genotypes also did not show any significant influence on the risk of ESCC and GCA development compared to A/A genotypes.CONCLUSION: IL-10-G1082A polymorphism might not be used as a stratification marker to predicate the risk of ESCC and GCA development in North China.

Single nucleotide polymorphism in DNA methyltransferase 3B promoter and its association with gastric cardiac adenocarcinoma in North China

AIM:To investigate the association between single nucleotide polymorphism (SNP) in promoter of the DNA methyltrans-ferase 3B(DNMT3B) gene and risk for development and lymphatic metastasis of gastric cardiac adenocarcinoma (GCA). METHODS: The hospital based case-control study included 212 GCA patients and 294 control subjects without overt cancer. The DNMT3B SNP was genotyped by PCR and restriction fragment length polymorphism (RFLP) analysis. RESULTS: The C/C genotype was not detected in both GCA patients and controls. In control subjects, the frequency of T/T and C/T genotypes was 94.9% and 5.1% respectively, and that of T and C alleles was 97.4% and 2.6%, respectively. The genotype and allelotype distribution in the GCA patients was not significantly different from that in controls (P=0.34 and 0.33, respectively). When stratified by smoking status and family history of upper gastrointestinal cancer, significant difference in the genotype distribution was not observed between GCA patients and controls. The distribution of DNMT3B genotypes in GCA patents with or without lymphatic metastasis did not show significant difference (P= 0.42). CONCLUSION: The distribution of DNMT3B SNP in North China is distinct from that in Caucasians. Although this SNP has been associated with susceptibility to lung, head, neck and breast cancer, it may not be used as a stratification marker to predict susceptibility and lymphatic metastasis of GCA, at least in the population of North China.

Therapeutic effects of combined oxaliplatin and S-1 in older patients with advanced gastric cardiac adenocarcinoma

AIM:To evaluate the effects and safety of combination chemotherapy with oxaliplatin (L-OHP) and S-1 (SOX regimen) in older patients with advanced gastric cardiac adenocarcinoma (GCA). METHODS: Seventy patients with advanced GCA were classified according to age into an older group (≥ 75 years) and a control group (< 75 years). The SOX regimen was administered to the two groups as follows: S-1 (40 mg/m2 po bid) on days 1 to 14 followed by a 7-d off period, plus L-OHP (65 mg/m2 iv) for 2 h on days 1 and 8 of a 21-d cycle. This regimen was repeat-ed for four to six cycles. Response and swallow statuses were evaluated after two cycles (6 wk). Effects and toxicity were evaluated four weeks after chemotherapy was completed. RESULTS: The response rate was 65.6% (21/32) in the older group and 68.4% (26/38) in the control group (χ2 = 0.062 and P = 0.804). Improvement in swallowing was 78.1% (25/32) in the older group and 76.3% (29/38) in the control group (χ2 = 0.032 and P = 0.857). Effi cacy was 68.8% (22/32) in the older group and 65.8% (25/38) in the control group (χ2 = 0.069 and P = 0.793). Toxicities were reversible and similar in both groups (P > 0.05). CONCLUSION: The SOX regimen is an effective, safe and well-tolerated regimen for older patients with advanced GCA.

Etiologic factors of gastric cardiac adenocarcinoma among men in Taiwan

AIM:To elucidate etiologic associations between Helicobacter pylori(H pylori),lifestyle,environmental factors and gastric cardiac adenocarcinoma(GCA)among men. METHODS:A hospital-based case-control study was conducted in Taiwan from 2000 to 2009.All cases were newly confirmed as primary GCA.Five controls were selected matching with age,sex,and admission date to each case.Participants were informedof potential risk factors with a structured question- naire by trained interviewers during hospitalization and provided a blood sample for the determination of H pylori infection.Odds ratio(OR)and 95%confidence interval(95%CI)were used to evaluate risk,and a multivariate conditional logistic regression model was performed. RESULTS:All participants recruited for this study were men,consisting of 41 cases and 205 controls.Results of the univariate analysis showed that significant factors associated with the etiology of GCA included H pylori(OR =2.69,95%CI=1.30-5.53),cigarette smoking(OR= 2.28,95%CI=1.05-4.96),working or exercising after meals(OR=3.26,95%CI=1.31-8.11),salted food (OR=2.51,95%CI=1.08-6.11),fresh vegetables(OR =0.28,95%CI=0.09-0.80),fruits(OR=0.19,95% CI=0.04-0.89),and rice as principal food(OR=0.53, 95%CI=0.30-0.85).Multivariate conditional logistic regression models indicated that a significantly elevated risk of contracting GCA was associated with working or exercising after meals(OR=3.18,95%CI=1.23-9.36) and H pylori infection(OR=2.93,95%CI=1.42-6.01). In contrast,the consumption of fresh vegetables(OR =0.22,95%CI=0.06-0.83),fruits(OR=0.28,95% CI=0.09-0.79)and rice as principal food(OR=0.48, 95%CI=0.24-0.93)remained as significant beneficial factor associated with GCA. CONCLUSION:Working or exercising after meals and H pylori infection increase the risk of GCA,but higher intakes of rice,fresh vegetables and fruits reduce the risk.

Long-term effects of proglumide on resection of cardiac adenocarcinoma

AIM:Patients with advanced stage cardiac adenocarcinoma have a very poor prognosis. Surgery is the first choice of treatment for this kind of patients. Peptide hormone gastrin is a recognized growth factor for gastric cancer, and gastrin receptor antagonist proglumide can block the effects of gastrin. The aim of this study was to investigate the actions of proglumide as an adjuvant treatment to improve the postoperative long-term survival rate of patients with cardiac adenocarcinoma. METHODS: We performed a randomized, controlled study of gastrin receptor antagonist proglumide in 301 patients with cardiac adenocarcinoma after proximal subtotal gastrectomy. The oral dose of 0.4 g proglumide thrice daily preprandially was maintained for more than 5 years in 153 cases (proglumide treatment group). In the control group, 148 patients underwent operation only. In clinicopathologic features, there was no significant difference between the two groups (P>0.05). All patients were followed up during their lifetime, and the survival rates were analyzed combined with clinicopathologic factors by SPSS 11.5 statistical software. RESULTS: The 1,3,5 and 10-year survival rate of the patients was 88.4%, 48.8%, 22.6% and 13.4%, respectively. The 1,3,5 and 10-year survival rate of the proglumide treatment group was 90.2%, 49.7%, 26.8% and 17.6% compared to 86.5%, 48.0%, 18.2% and 8.9% of the control group. There was a significant difference between the two groups (P= 0.0460). The patients in proglumide treatment group had no obvious side effects after administration of the drug, and no definite hepatic and renal function damage was found. According to single factor log-rank analysis, the long-term survival rate was correlated with the primary tumor position (P= 0.0205), length of the tumor (P= 0.0000), property of the operation (P= 0.0000), histopathologic grading (P = 0.0003), infiltrating degree of the tumor (/>= 0.0000), influence of lymph node metastasis (P = 0.0000), clinicopathologic staging (P= 0.0000) and administration of proglumide (P = 0.0460). Cox regression analysis demonstrated the infiltrating degree of tumor (P= 0.000), influence of lymph node metastasis (P= 0.039) and the clinicopathologic staging (P = 0.003) were independent prognostic factors. Administration of proglumide (P= 0.081), length of the tumor (P = 0.304), radical status of the resection (P= 0.224) and histopathologic types (P= 0.072) were not the independent prognostic factors. CONCLUSION: Proglumide is convenient to use with no obvious toxic side effects, and prolonged postoperative administration of proglumide as a postoperative adjuvant treatment can increase the survival rate of patients after resection of cardiac adenocarcinoma. Proglumide may provide a new effective approach of endocrinotherapy for patients with gastric cardiac cancer.

Polymorphisms in tumor necrosis factor genes and susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma in a population of high incidence region of North China

Background We investigated the possible association of the functional polymorphisms in the tumor necrosis factor （TNF） genes with susceptibility to esophageal squamous cell carcinoma （ESCC） and gastric cardiac adenocarcinoma （GCA）.Methods The TNF-α-308G/A and TNF-β ＋ 252G/A single nucleotide polymorphisms （SNPs） were genotyped using polymerase-chain reaction-restriction fragment length polymorphism （PCR-RFLP） analysis, in 555 cancer patients （291 ESCC and 264 GCA） and 437 healthy controls in a high incidence region of North China. Results Among healthy controls, frequencies of the TNF-α 1/1, 1/2 and 2/2 genotypes were 89.4% ,9.2% and 1.4% respectively, while frequencies of the TNF-β B1/B1, B1/B2 and B2/B2 genotypes were 12.6% , 32.3% and 55.1%, respectively. No significant difference was found in the overall genotype and allelotype distribution of the TNF-α-308G/A and TNF-β ＋ 252G/A SNPs among cancer patients and controls. However, both the B1/B1 genotype and B1/B2 genotype significantly increased the risk of developing ESCC [ the age and gender adjusted odds ratio （OR） =2.04 and 1.91, 95% confidence interval （CI） = 1.04 -4.43 and 1.14 - 2.60, respectively] and GCA （the age and gender adjusted OR =2. 68 and 2. 64, 95% CI = 1.14 -6.29 and 1.47 -4.72, respectively） in individuals with negative family history of UGIC, in comparison with the B2/B2 genotype. When the two TNF polymorphisms were combined and analyzed, individuals with the TNF-β B1/B2 and TNF-α1/2 or 2/2 genotypes significantly reduced the risk of developing ESCC and GCA, in comparison with those harboring the TNF-β B2/B2 and TNF-α 1/1 genotypes （ the age and gender adjusted OR = 0.37 and 0. 34, 95% CI =0. 15 -0.92 and 0. 13 -0.90, respectively）. Conclusions Therefore, the TNF-α -308G/A and TNF-β ＋ 252G/A genotyping may be used as a stratification markers to predicate the risk of ESCC and GCA development in North China.

Significance and prognostic value of lysosomal enzyme activities measured in surgically operated adenocarcinomas of the gastroesophageal junction and squamous cell carcinomas of the lower third of esophagus

AIM： To establish whether there are fundamental differences in the biochemistries of adenocarcinomas of the gastroesophageal junction （GEJ） and the squamous cell carcinomas of the lower third of the esophagus （LTE）. METHODS： Between February 1, 1997 and February 1, 2000, we obtained tissue samples at the moment of resection from 54 patients for biochemical analysis. The full set of data could be comprehensively analyzed in 47 of 54 patients＇ samples （81%）. Of these, 29 were adenocarcinomas of the GEJ Siewert type Ⅰ （n = 8）, type Ⅱ （n = 12）, type Ⅲ （n = 9）, and 18 presented as squamous cell carcinomas of the LTE. We evaluated the mean values of 11-lysosomal enzyme and 1-cytosol protease activities of the tumorous and surrounding mucosae as well as their relative activities, measured as the ratio of activity in tumor and normal tissues from the same patient. These data were further analyzed to establish the correlation with tumor localization, TNM stage （lymph-node involvement）, histological type （papillary, signet-ring cell, tubular）, state of differentiation （good, moderate, poor）, and survival （≤24 or ≥24 mo）. RESULTS： In adenocarcinomas, the activity of α-mannosidase （AMAN）, cathepsin B （CB） and dipeptidyl-peptidase Ⅰ （DPP Ⅰ） increased significantly as compared to the normal gastric mucosa. In squamous cell carcinomas of the esophagus, we also found a significant difference in the activity of cathepsin L and tripeptidyl-peptidase Ⅰ in addition to these three. There was a statistical correlation of AMAN, CB, and DPP Ⅰ activity between the level of differentiation of adenocarcinomas of the GEJ and lymph node involvement,because tumors with no lymph node metastases histologically confirmed as well-differentiated, showed a significantly lower activity. The differences in CB and DPP Ⅰ activity correlated well with the differences in survival rates, since the CB and DPP Ⅰ values of those who died within 24 mo following surgical intervention were significantly higher than of those who survived for 2 years or more. CONCLUSION： Adenocarcinomas of the GEJ form a homogenous group from a tumor-biochemical aspect, and differ from the biochemical characteristics of squamous cell carcinomas of the LTE on many points. When adenocarcinomas of the GEJs are examined at the preoperative phase, the ratio of the performed AMAN, CB, and DPP Ⅰ enzymatic activity of the tissue sample from the tumor and adjacent intact mucosa within 2 cm of the tumor may have a prognostic value even in the preoperative examination period, and may indicate that ranking of these patients into the neo-adjuvant treatment group should be considered.

血清肺腺癌转录相关转录本1、微RNA-1水平与心肌梗死继发室性心律失常的关系研究

目的探讨血清肺腺癌转录相关转录本1(MALAT1)、微RNA-1(miR-1)水平与急性心肌梗死(AMI)继发室性心律失常(VA)的关系。方法选取2019年10月至2021年6月临汾市中心医院收治的AMI病人270例,均行经皮冠状动脉介入治疗(PCI)治疗,术后进行24 h动态心电图监测,根据Lown分级将病人分为心律正常组(0级,166例)和心律失常组(1~5级,104例)。收集所有病人一般资料,实时荧光定量逆转录聚合酶链反应(qRT-PCR)法检测血清MALAT1、miR-1水平,Pearson法分析AMI继发VA病人血清MALAT1水平与miR-1水平的相关性,采用受试者操作特征(ROC)曲线分析血清MALAT1、miR-1水平对AMI病人继发VA的诊断价值,并分析AMI病人继发VA的影响因素。结果心律失常组心肌标志物肌酸激酶同工酶(CK-MB)、血清N末端脑钠肽前体(NT-proBNP)、心肌肌钙蛋白(cTnI)、左心室舒张末期内径(LVEDD)水平、Gensini积分、右冠脉病变比例及血清MALAT1(1.28±0.34)、miR-1(1.24±0.33)水平明显高于心律正常组(1.01±0.12、0.99±0.10)(P<0.05),左心室射血分数(LVEF)水平明显低于心律正常组(P<0.05);心律失常5级、4级病人血清MALAT1(1.76±0.47、1.45±0.40)、miR-1(1.69±0.43、1.40±0.39)水平明显高于3级(1.12±0.30、1.09±0.31)、2级(1.08±0.29、1.05±0.26)、1级(1.04±0.27、1.02±0.25)病人(P<0.05),心律失常5级病人血清MALAT1(1.76±0.47)、miR-1(1.69±0.43)水平明显高于4级(1.45±0.40、1.40±0.39)病人(P<0.05);AMI继发VA病人血清MALAT1水平与miR-1水平呈正相关(P<0.05);血清MALAT1、miR-1水平诊断AMI继发VA的曲线下面积分别为0.77、0.81,灵敏度分别为69.2%、73.1%,特异度分别为81.9%、88.0%,最佳截断值分别为1.13、1.15;二者联合诊断AMI继发VA的曲线下面积、灵敏度、特异度分别为0.90、84.6%、86.7%,二者联合诊断的曲线下面积高于二者单独诊断(P<0.05);logistic回归分析结果显示,高CK-MB、高NT-proBNP、高cTnI、高LVEDD、高Gensini积分、右冠脉病变、低LVEF及血清MALAT1高表达、miR-1高表达为AMI病人继发VA的独立危险因素(P<0.05)。结论AMI继发VA病人血清MALAT1、miR-1水平升高,二者均为AMI病人继发VA的独立危险因素,可用于诊断AMI病人是否继发VA,联合检测诊断价值更高。

E-钙粘蛋白基因多态性与食管癌、贲门癌的关系

背景与目的:E-钙粘蛋白(E-cadherin,CDH1)是钙粘蛋白家族中的一个成员,与肿瘤侵袭转移密切相关。该基因启动子区存在的多态性位点可通过改变转录活性而影响该蛋白的表达。本研究旨在探讨该基因启动子区C-160A和G-347GA单核苷多态性(single nucleotide polym orphism,SNP)与中国北方人食管鳞状细胞癌(esophagealsquam ous cellcarcinom a,ESCC)、贲门腺癌(gastric cardiacadenocarcinom a,GCA)易感性和淋巴结转移的关系。方法:采用聚合酶链反应-限制性片段长度多态性(polym erase chain reaction-restrictionfragm entlength polym orphism,PCR-RFLP)分析方法检测333名ESCC患者、239名GCA患者和343名健康对照的CDH1C-160A及G-347GA SNP的基因型。结果:CDH1C-160A及G-347GA SNP的基因型及等位基因型分布在总体ESCC患者、GCA患者和健康对照中无显著性差异(P=0.08)。根据吸烟状况及上消化道肿瘤家族史分层分析及淋巴结转移状况的分析也未发现CDH1SNPs对ESCC和GCA发病及淋巴结转移的影响。然而,与G-347GA G/G基因型相比,携带GA等位基因(G/GA+GA/GA基因型)可显著增加GCA患病风险,经性别、年龄校正后的OR值为1.45(95%CI=1.03～2.04)。应用EH软件分析显示。

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。

微血管密度及血管内皮生长因子在贲门癌中的表达及其意义

目的 探讨贲门癌组织中微血管密度及血管内皮生长因子 (VEGF)的表达与其生物学行为的关系。方法 对 4 8例具有较完整临床病理资料的贲门癌组织 ,进行了CD34、VEGF免疫组织化学SP法检测 ,分析VEGF和微血管密度 (MVD)与贲门癌的分化程度、临床分期、淋巴结转移的关系。结果 VEGF阳性表达与MVD均与癌组织分化程度、临床分期、淋巴结转移有相关性(P <0 .0 5 ) ,并且在VEGF阳性表达的肿瘤中 ,MVD明显高于阴性者 (P <0 .0 5 )。结论 VEGF与贲门癌的血管生成密切相关 ,对肿瘤生长、浸润和转移有促进作用。VEGF和MVD可作为预测贲门癌生物学行为指标之一。

贲门腺癌Wif-1基因启动子区甲基化状态的检测及临床意义

目的研究贲门腺癌(gastric cardiacadenoc arcinoma,GCA)中Wnt抑制因子-1(Wntinhibitory factor-1,Wif-1)基因启动子区甲基化状态及表达情况,探讨其与贲门癌发生的关系及可能机制。方法分别用巢式甲基化特异性PCR(MSP)和RT-PCR方法检测贲门腺癌及相应正常黏膜组织中Wif-1基因的甲基化状态和mRNA表达水平;应用免疫组化S-P法检测β-catenin蛋白的表达情况。结果Wif-1基因在贲门腺癌及正常黏膜组织中的甲基化率分别61.7%(58/94)和34.0%(32/94),癌组织中Wif-1基因的甲基化率明显高于正常黏膜组织(χ2=14.409,P=0.000);癌及正常黏膜组织中Wif-1基因mRNA的阳性表达率分别为10.6%(10/94)和86.2%(81/94),β-catenin蛋白的异质表达率分别为90.4%(85/94)和38.3%(36/94),癌组织中Wif-1mRNA表达及β-catenin蛋白的表达均与Wif-1基因的甲基化明显相关(P<0.01);Wif-1基因的甲基化与肿瘤的浸润深度及淋巴结转移相关(P<0.05),而与肿瘤的病理分级及临床分期无关。结论Wif-1基因启动子区甲基化在贲门腺癌中频繁发生,可能通过引起经典Wnt/β-catenin通路的异常激活与贲门腺癌的发生密切相关。

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、责门癌高发区一磁县、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基因型频率分剐是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（χ^2=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％C=0.0．94～4．83）。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／O基因型可能是吸烟人群GCA发病的危险因素。

17例早期贲门腺癌患者的自然生存状况追踪分析

背景与目的:未经治疗的晚期贲门腺癌患者的生存时间为8～9个月,本研究目的是观察未进行任何治疗的早期胃贲门腺癌的自然发展史。方法:1987年在食管癌高发现场,对细胞学诊断为鳞状细胞重度增生的851例进行了内镜复查,同时检查了贲门区粘膜,经活检病理确诊为贲门腺癌者共43例,包括晚期癌12例,早期癌31例。其中17例早期患者虽经多次劝说,仍因不同原因拒绝治疗,随诊观察14年,直至全部患者死亡。结果:随诊14年,17例早期贲门癌患者中,12例死于贲门腺癌,另外5例死于非癌疾病;生存5年以上者13例,5年自然生存率为76.47%(13/17),10年自然生存率为23.53%(4/17)。结论:早期贲门癌发展到晚期是一个漫长的演进过程。这对早期诊断和选择治疗时机很有帮助。同时,如要精确评估早期癌治疗效果,宜充分考虑其自然史的因素。

XPA基因多态性与食管癌、贲门癌发病风险的关联

目的探讨XPA基因5’-非编码区转录启始密码子ATG上游第4位A23G和228密码子G709A单核苷酸多态性(Singlenucleotidepolymorphism,SNP)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(Esophagealsquamouscellcarcinoma,ESCC)和贲门腺癌(Gastriccardiacadenocarcinoma,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名ESCC患者、253名GCA患者和612名健康对照的XPAA23G和G709ASNP的基因型。结果XPA基因A23G的等位基因和基因型频率在ESCC和健康对照之间,总体分布有显著性差异。与A/A基因型相比,A/G+G/G基因型可显著降低ESCC的发病风险。分层分析显示,此保护作用在非吸烟组和吸烟组人群中尤为明显。此保护作用在UGIC家族史阴性人群中也很明显。在GCA和健康对照之间,A23G等位基因频率和基因型频率总体分布无显著性差异(P>0.05)。与A/A基因型相比,A/G+G/G基因型可显著降低GCA的发病风险。分层分析显示,在非吸烟组中,GCA患者组和健康对照之间,基因型频率分布有显著性差异(P<0.05)。与A/A基因型相比,A/G+G/G基因型可显著降低非吸烟人群GCA的发病风险。结论XPA基因A23G含突变等位基因(G)的基因型(A/G+G/G)可能是影响河北省食管癌、贲门癌的高发区——磁县和涉县人群ESCC发病风险的因素之一。

三磷酸腺苷结合盒转运体G2与CD_(24)在贲门腺癌中的表达及临床意义研究

目的检测肿瘤干细胞标志物三磷酸腺苷结合盒转运体G2(ABCG2)和CD24在贲门腺癌中的表达情况,探讨两者与腺癌临床病理特征间的关系。方法采用免疫组化法检测140例贲门腺癌组织和15例癌旁组织中AB-CG2和CD24的表达情况。将所收集的病例依据不同的分化程度、年龄、性别、肿瘤浸润深度、TNM分期及病理学形态进行分组,观察二者的阳性表达率,采用χ2检验分析两者与临床及病理特征间的相关性,进一步探讨ABCG2和CD24与贲门腺癌恶性程度的关系。结果免疫组化结果显示ABCG2和CD24在腺癌组织中的阳性表达率分别为54.3%(76/140)和45.0%(63/140),均高于癌旁组织〔13.3%(2/15)和6.7%(1/15)〕,差异有统计学意义(P<0.05)。ABCG2的阳性表达率与肿瘤分化程度及Lauren分型有相关性(P<0.05);与患者的年龄、性别、浸润程度、淋巴结转移、临床分期无相关性(P>0.05)。CD24的阳性表达率不仅随分化程度升高表达下调,还与浸润程度、淋巴结转移、临床分期及Lauren分型有相关性(P<0.05),但与患者的年龄、性别无相关性(P>0.05)。结论 ABCG2、CD24与肿瘤干细胞存在密切相关性。ABCG2只与肿瘤的分化程度及病理形态学分型关系密切。CD24与肿瘤的分化程度、浸润深度、淋巴结转移、临床分期及Lauren分型关系密切,提示两者可能参与贲门腺癌的恶性过程,其表达越高患者的预后可能越差。

贲门癌术前短期化疗与远期生存的探讨

目的： 探讨贲门癌术前短期化疗与远期生存的关系。方法： 贲门腺癌患者６０ 例， 随机分成用药组与对照组，每组３０ 人。用药组术前分次服用氟脲嘧啶多相脂质体，总剂量为５００ｍｌ。对两组手术切除标本进行大体和病理组织学检查，以及流式细胞荧光ＤＮＡ 凋亡细胞率的检测。结果：与对照组比较，用药组肿瘤体积缩小。癌细胞发生显著的退行性变和坏死。ＤＮＡ 凋亡细胞率明显高于对照组 （ Ｐ＜ ０ ．００１） 。５ 年生存率， 用药组为４０ ．０ ％ ， 对照组为２３ ．３ ％ 。结论：上述结果表明贲门癌患者术前短期服用氟脲嘧啶多相脂质体能提高术后５ 年生存率。

贲门腺癌中RASSF1A基因的甲基化状态及表达

目的研究贲门腺癌(gastric cardiac adenocarcinoma,GCA)中RASSF1A基因的甲基化状态及其蛋白表达情况。方法分别应用甲基化特异性PCR(MSP)、RT-PCR及免疫组织化学SP法检测贲门癌组织及相应癌旁组织的RASSF1A甲基化情况和mRNA水平及蛋白表达情况。结果92例贲门癌组织中有54例发生了甲基化,甲基化率为58.7%,显著高于癌旁正常组织(P<0.01)。Ⅲ期和Ⅳ期贲门癌患者中RASSF1A基因发生甲基化的比率显著高于Ⅰ期和Ⅱ期患者(P<0.05)。92例贲门癌组织中有43例RASSF1A基因蛋白表达阴性,与相应癌旁正常组织相比有显著性差异(P<0.01)。Ⅲ期和Ⅳ期贲门癌RASSF1A基因蛋白表达显著低于Ⅰ期和Ⅱ期患者(P<0.05)。发生甲基化的贲门癌组织中RASSF1A的mRNA水平的表达显著低于未发生甲基化的贲门癌组织(P<0.01)。结论RASSF1A基因启动子区发生甲基化导致的基因沉默可能是贲门腺癌发生的机制之一。

贲门腺癌中CD24的表达及临床意义

目的 检测肿瘤干细胞标志物CD24在140例贲门腺癌中的表达,探讨其与腺癌临床病理学参数的关系。方法 采用免疫组化SP法检测140例贲门腺癌中CD24的表达,分析其与临床病理学特征及生物学行为之间的相关性; 收集新鲜癌组织与癌旁组织各26例,依据不同临床分期、不同分化程度进行分组,分别提取两组中的总RNA进行RT-PCR检测,计算CD24的相对表达量,分析两组间的差异性,进一步分析二者的侵袭性。结果（1）免疫组化检测结果：CD24在癌组织中的表达高于癌旁组织（P〈0.05）。CD24在低分化腺癌中的表达高于中＋高分化腺癌（P〈0.05）。CD24与肿瘤的浸润深度、淋巴结转移情况、临床分期及神经受侵密切相关（P〈0.05）,与患者年龄、性别,有无瘤栓及残端状况无关（P〉0.05）。CD24在两种病理形态学分型中的表达,Lauren分型：弥漫型高于肠型; WHO分型：管状腺癌、乳头状腺癌、黏液腺癌及低黏附型癌之间存在差别,差异有统计学意义（P〈0.05）。（2）RT-PCR检测结果：CD24在贲门腺癌中的表达高于癌旁组织（P〈0.05）,在癌旁组织中微量表达。低分化组相对表达量高于中＋高分化组（P〈0.05）。CD24表达与临床分期相关,腺癌中Ⅰ～Ⅳ期CD24 mRNA的相对表达量逐级升高,差异有统计学意义（P〈0.05）,结果与免疫表型一致。结论 CD24与肿瘤的分化程度、浸润深度、淋巴结是否转移及临床分期密切相关,提示CD24可能参与贲门腺癌的恶性过程,其表达越高肿瘤分化越差。

XRCC1基因多态性与贲门癌的发病风险

目的通过病例-对照研究,探讨X-射线交错互补修复基因1(X-ray repair cross-complementing gene1,XRCC1)基因多态性与贲门腺癌(gastric cardiac adenocarcinoma,GCA)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技术检测455例GCA患者和650例对照人群XRCC1Arg194Trp、Arg280His及Arg399Gln3个多态性位点基因型和等位基因频率分布情况。结果XRCC1Arg194Trp及Arg399Gln多态位点的基因型及等位基因型频率的分布在患者组和对照组之间无明显的差异(P>0.05)。但以吸烟和家族史状况分层分析发现,吸烟组中GCA患者280位点的His等位基因频率为11.5%,明显高于对照组8.2%,GCA患者组和健康对照组中Arg/Arg、Arg/His、His/His三种基因型频率分别是77.9%、21.2%、0.9%和84.9%、13.7%、1.4%,两组相比差异具有统计学意义(χ2=4.107,P=0.043)。与Arg/Arg基因型相比,携带His等位基因(Arg/His+His/His)可明显增高吸烟人群GCA的发病风险(OR=1.572,95%CI=1.00～2.51)。结论本研究结果提示XRCC1基因Arg194Trp、Arg399Gln多态位点可能与GCA的发病风险无关,但Arg280His多态的His等位基因型可能增加吸烟人群GCA的发病风险。