CYP1A1与GSTM1基因多态性与前列腺癌易感性的关系

目的　探讨CYP1A1、GSTM1基因多态性与前列腺癌遗传易感性的关系。　方法　采用寡核苷酸芯片对 83例前列腺癌患者和 115例正常对照的中国汉族人群基因组DNA进行CYP1A1、GSTM1基因多态性分析。　结果　GSTM1基因缺失型前列腺癌组占 5 7.8% ,对照组 4 1.7% ,差异有显著性意义 ( χ2 =4 .99,P =0 .0 2 5 ) ,GSTM1null基因型使患前列腺癌的危险度增加 1.9倍 ( 95 %CI=1.10～ 1.34)。GSTM1基因缺失型前列腺癌患者的平均年龄 [( 6 8.1± 8.3)岁 ]低于GSTM1未缺失的患者[( 71.9± 7.4 )岁 ,P =0 .0 31]。前列腺癌组CYP1A1基因的两个多态位点m1、m2基因型频率和等位基因的频率与对照组相比差异无显著性意义 (P >0 .0 5 )。　结论　中国汉族人群GSTM1基因多态性与前列腺癌的发生相关 ,可能是增加前列腺癌危险和发病年龄早的因素之一。CYP1A1基因m1和m2的基因多态与中国汉族人群前列腺癌的发生无相关性     

前列腺癌发生风险与CYP3A5基因多态性的关系

目的 探讨CYP3A5基因多态性与前列腺癌发生风险和病理特点的关系。方法 采用限制性片段多态性分析法对356例前列腺癌患者和306个男性对照中CYP3A5基因第3内含子多态性进行了研究。结果 在前列腺癌和对照组之间CYP3A5基因型分布差异无显著性(P=0．063)，但两组间CYP3A5*1等位基因的分布差异存在显著性(P=0．025)；与携带CYP3A5*3*3基因型者相比，携带CYP3A5*1等位基因的男性患前列腺癌的风险降低了30％(P=0．026)。在不同分期和分级的前列腺癌患者之间CYP3A5基因型分布差异无显著性(P=0．904和0．986)。结论 CYP3A5基因中的CYP3A5*1等位基因可能与前列腺癌的患病风险降低有关。     

中国汉族男性CYP17基因多态性与前列腺癌发生危险性的关系

目的　探讨CYP1 7基因多态性与前列腺癌发生危险性的关系。　方法　提取 1 2 5例前列腺癌患者和 1 5 8例对照组的血DNA标本 ,设计引物通过PCR技术扩增出包括基因多态位点的片段 ,用限制性内切酶MspA1Ⅰ进行酶切 ,产物在 2 %琼脂糖凝胶上电泳 ,确定出CYP1 7基因的 3种基因型 ,即A1 /A1、A1 /A2、A2 /A2 ,并经测序证实。　结果　基因型A1 /A2、A2 /A2频数与A1 /A1基因型进行比较 ,A1 /A2和A2 /A2在前列腺癌中的频数与对照组相比 ,其OR值分别为 1 .1 9和 1 .2 8,P值分别为 0 .5 7和 0 .4 5 ;但年龄 >6 9岁的病例中 ,其OR值分别为 3.97和 3.2 1 ,P值分别为 0 .0 0 7和 0 .0 2 3;对照组的血fPSA、tPSA水平 3组间差异无显著性意义。　结论　A1 /A2、A2 /A2基因型未增加汉族人群前列腺癌发生的危险性 ,基因型间血PSA水平差异无显著性支持这一观点。年龄 >6 9岁的人群中 ,A1 /A2、A2 /A2基因型显著增加前列腺癌发生的危险性 ,提示CYP1 7基因可能与老年男性前列腺癌发生危险性之间有密切关系     

胰岛素降解酶基因单核苷酸多态性与前列腺癌的关系研究

目的研究胰岛素降解酶(IDE)基因单核苷酸多态性与前列腺癌之间的关系。方法运用TaqMan探针SNP分析法测定192例胰腺癌患者和258例正常对照IDE基因rs4646953和rs2251101两个位点基因型,并分析IDE基因多态性与前列腺癌的关系。结果病例组IDE基因rs4646953位点TT、CT以及CC3种基因型等位基因频率分别为85.4%、14.1%和0.5%;对照组3种基因型等位基因频率分别为88.4%、10.1%和1.6%。病例组rs2251101位点TT、CT以及CC3种基因型频率分别为81.8%、16.7%和1.6%;对照组3种基因型等位基因频率分别为73.6%、23.3%和3.1%。病例组IDE基因rs4646953位点的基因型分布与正常对照组比较未见统计学差异(P=0.348),rs2251101位点病例组CT和CC基因型低于正常对照组(P=0.039)。结论 IDE基因rs2251101位点变异与前列腺癌相关。     

N-乙酰基转移酶2基因多态性与染发皮炎易感性关系

目的 探讨N-乙酰基转移酶2（NAT2）基因多态性与中国人染发皮炎遗传易感性的关系.方法 应用聚合酶链反应（PCR）及限制性片段长度多态性（RFLP）技术检测和分析天津地区60例染发皮炎患者及73例正常对照者的NAT2野生型等位基因（NAT2＊4）和3个常见突变位点（NAT2＊5A,NAT2＊6B和NAT2＊7A）的基因多态性,比较NAT2各等位基因及基因型频率在染发皮炎组与对照组间分布差异.结果 NAT2等位基因NAT2＊4,NAT2＊5A,NAT2＊6B和NAT2＊7A在染发皮炎组中的分布频率分别是52.5%,5.0%,26.7%,15.8%,在对照组中为55.5%,3.4%,27.4%,13.7%,两组相比差异均无统计学意义（P〉0.05）;快型、中间型、慢型基因型在染发皮炎组中频率分别是26.7%,51.7%,21.7%,在对照组中为30.1%,50.7%,19.2%,与对照组相比差异无统计学意义（P〉0.05）.结论 NAT2基因多态性与中国汉族人染发皮炎遗传易感性无关.     

湖北地区汉族人群维生素D受体基因起始密码单核苷酸多态性与前列腺癌的相关性分析

目的 :了解维生素D受体 (vitaminDreceptor,VDR)基因起始密码单核苷酸多态性与前列腺癌的关系 ,探讨前列腺癌发病的分子机制。　方法 :提取 80例前列腺癌患者及 96例健康男性对照者外周血标本中基因组DNA ,应用聚合酶链反应 限制性片段长度多态性 (PCR RFLP)及DNA测序技术检测并分析了VDR基因起始密码单核苷酸多态性在两组中的分布。　结果 :前列腺癌病例和对照组FokⅠ等位基因频率分布均符合Hardy Weinberg定律 ,其FokⅠ多态位点FF、Ff、ff基因型分布频率分别为 32 .5 %、5 0 .0 %、17.5 %和 2 5 .0 %、5 3.13%、2 2 .87% ;等位基因F、f分布频率分别为 4 5 %、5 5 %和 5 1.5 6 %、4 8.4 4 % ,在湖北地区汉族前列腺癌患者及对照者中的分布频率差异无显著性 (P >0 .0 5 )。　结论 :VDR基因起始密码的单核苷酸多态性可能与低发病的湖北地区汉族人群的前列腺癌发生无关。     

北方汉族人群维生素D受体基因Bsm I位点多态性与前列腺癌易感性的相关性分析

目的 :研究低发病的中国汉族人群维生素D受体基因 (VDRG)BsmⅠ 位点单核苷酸多态性 (SNP)与前列腺癌的关系 ,探讨不同种族前列腺癌发病的基因差异。　方法 :收集中国北方地区汉族人群 10 3例前列腺癌病人及10 6例健康对照者外周血标本 ,应用变性高效液相色谱 (DHPLC)检测VDRG第 8内含子BsmⅠ多态位点 ,并对该位点SNP分布进行分析。　结果 :BsmⅠ 多态位点bb、Bb、BB基因型和等位基因在北方地区汉族前列腺癌病人及对照者中的分布频率差异无显著性 (P >0 .0 5 ) ,基因型分布频率分别为 92 .2 3%、7.77%、0和 94.34 %、5 .6 6 %、0 ;等位基因B、b分别为 3.88%、96 .12 %和 2 .91%、97.0 9%,而与高发病人群的分布相比有显著不同。　结论 :VDRGBsmⅠ多态性在低发病的中国汉族人群与前列腺癌无相关 ,其分布与高发病人群有明显差异 ,提示VDRGBsmⅠ多态性可能是前列腺癌发病种族差异的原因之一。     

北方汉族人群维生素D受体基因BsmⅠ位点多态性与前列腺癌易感性的相关性分析

目的 :研究低发病的中国汉族人群维生素D受体基因 (VDRG)BsmⅠ 位点单核苷酸多态性 (SNP)与前列腺癌的关系 ,探讨不同种族前列腺癌发病的基因差异。　方法 :收集中国北方地区汉族人群 10 3例前列腺癌病人及10 6例健康对照者外周血标本 ,应用变性高效液相色谱 (DHPLC)检测VDRG第 8内含子BsmⅠ多态位点 ,并对该位点SNP分布进行分析。　结果 :BsmⅠ 多态位点bb、Bb、BB基因型和等位基因在北方地区汉族前列腺癌病人及对照者中的分布频率差异无显著性 (P >0 .0 5 ) ,基因型分布频率分别为 92 .2 3%、7.77%、0和 94.34 %、5 .6 6 %、0 ;等位基因B、b分别为 3.88%、96 .12 %和 2 .91%、97.0 9%,而与高发病人群的分布相比有显著不同。　结论 :VDRGBsmⅠ多态性在低发病的中国汉族人群与前列腺癌无相关 ,其分布与高发病人群有明显差异 ,提示VDRGBsmⅠ多态性可能是前列腺癌发病种族差异的原因之一。     

生物转化酶基因多态性与前列腺癌易感性的研究

目的 探讨生物转化酶类细胞色素P450（CYP）基因CYP1A1m1、m2和谷胱甘肽转硫酶（GST）M1基因多态性与前列腺癌易感性的关系。方法 采用寡核苷酸芯片对83例前列腺癌患者（前列腺癌组）和115例非前列腺癌对照者（对照组）的中国汉族人基因组DNA进行CYP1A1、GSTM1基因多态性分析。结果 GSTM1缺失型在前列腺癌组和对照组均为48例（57．8％,41．7％）,两组比较差异有统计学意义（X^2=4．99,P=0．025）,GSTMl缺失型使患前列腺癌的危险度增加1．9倍（95％CI=1．10～3．40）。GSTM1缺失型随着前列腺癌的分期、分级的提高,其相对危险度明显提高。前列腺癌组CYP1A1基因的两个多态位点m1、m2基因型频率和等位基因的频率与对照组相比均无统计学意义（P〉0．05）。结论 中国汉族人群GSTM1缺失型可能与前列腺癌的发病风险相关,与前列腺癌的分级、分期有关,对临床预测前列腺癌预后可能有一定意义。     

马兜铃酸肾病与代谢酶基因多态性的相关性研究

目的：探讨依赖还原型辅酶Ⅰ/Ⅱ醌氧化还原酶（NQO1）和细胞色素P450 1A1（CYP1A1）基因多态性与马兜铃酸肾病（AAN）的相关性。方法：应用双相引物-聚合酶链反应（PCR-CTPP）,对90例AAN患者和159例健康对照组进行NQO1基因609位点和CYP1A1基因4889位点单核苷酸多态性的检测,比较两组基因型分布频率的差异。并将病例组按不同基因型分组,分析不同基因型与临床表现的关系。Logistic回归检验AAN患者发生重度贫血的影响因素。结果：CYP1A1A4889G基因型和等位基因分布频率在两组间差异均无统计学意义（P〉0.05）。AAN组NQO1C609T低表达基因型（TT＋CT）分布频率高于对照组（76.7%vs65.4%,P〈0.05）;TT基因型患者重度贫血的发生率明显增高（P〈0.05）;Logis-tic回归分析提示NQO1C609T低表达基因型为AAN患者重度贫血的危险因素。结论：NQO1 C609T基因多态性与马兜铃酸肾病的发病有关,并且可能增加了AAN患者早期重度贫血的风险。     

N-acetyltransferase-2 gene polymorphism as a possible biomarker for prostate cancer in Japanese men

BACKGROUND: The purpose of this study was to determine the frequency of a polymorphism of the candidate metabolic enzyme N-acetyltransferase-2 (NAT2) in Japanese prostate cancer patients and Japanese non-cancer controls, in order to determine if an association exists between NAT2 genotype and the occurrence, clinical stage and grade of prostate cancer. METHODS: In the present case-control study, 111 patients with prostate cancer and 152 controls were genotyped for the NAT2 polymorphism using the polymerase chain reaction-based restriction fragment length polymorphism method. The NAT2 genotypes (slow or rapid acetylator genotype) were determined by the combination of three known NAT2 mutant alleles (M1, M2, M3) and the wild-type allele. RESULTS: The NAT2 slow acetylator genotype was statistically higher among prostate cancer patients (17.1%) compared with controls (8.6%) (Odds ration (OR) = 2.21; 95% confidence interval (CI), 1.04-4.69; P = 0.0289). In addition, there was a statistically increased risk of prostate cancer among smokers with the NAT2 slow genotype (OR = 3.78: 95% CI, 1.48-9.66; P = 0.0041). Furthermore, the NAT2 slow acetylator genotype was significantly higher among prostate cancer patients with locally advanced and metastatic disease (22.7%) compared with controls (8.6%) (OR = 3.14; 95% CI, 1.40-7.06; P = 0.0051). Lastly, the NAT2 slow acetylator genotype was significantly higher among prostate cancer patients with high-grade tumors (31.4%) compared with controls (8.6%) (OR = 4.90; 95% CI, 1.97-12.20; P = 0.0010). CONCLUSION: These data demonstrate that the NAT2 slow acetylator genotype plays an important role in determining the risk of developing prostate cancer in Japanese men and is also associated with more clinically advanced and pathologically aggressive disease. Furthermore, a possible interaction between the NAT2 slow acetylator genotype and smoking status was suggested.     

Acetylation genotype and the genetic susceptibility to prostate cancer in a southern European population

BACKGROUND: Epidemiologic studies have suggested that environmental factors and diet are important risk factors in the pathogenesis of prostate cancer. The N-acetyltransferases (NAT) are important enzymes in activation and inactivation of various carcinogens, including those found in well-cooked meat and cigarette smoke. METHODS: We analyzed DNA samples from 146 prostate cancer patients and 174 healthy men. We used PCR-RFLP method to analyze NAT 1 and NAT 2 polymorphisms. RESULTS: We did not find statistically significant differences in NAT 1 genotypes frequencies between prostate cancer patients and control group. We observed an association of the slow acetylator genotype, NAT 2*6/NAT2*6 with prostate cancer protection (P=0.017; OR=0.31, 95% CI 0.11--0.84). Multivariate logistic regression analysis confirmed this association (0.030; OR=0.32, 95% CI 0.12--0.89). CONCLUSIONS: Our results indicate a role of NAT2 polymorphisms in the carcinogenic pathway of prostate cancer, specifically in a population of Southern Europe.     

Polymorphisms of GSTP1 and related genes and prostate cancer risk

Glutathione S-transferase P1 (GSTP1) is markedly downregulated in prostate cancer and prostatic intraepithelial neoplasia compared to normal prostate tissue. Downregulation of GSTP1 may, therefore, be an early event in prostate carcinogenesis. An A-->G polymorphism at nucleotide 313 results in an amino acid substitution (Ile105Val) in the substrate binding site of GSTP1 and reduces catalytic activity of GSTP1. In a study of 36 prostate cancer patients, Harries et al. reported that the Ile/Ile genotype is associated with a decreased risk of prostate cancer (odds ratio 0.4 (0.17-0.82)). We sought to confirm this finding and to examine the impact of this polymorphism together with several related polymorphisms implicated as risk factors for carcinogen-associated malignancies. One hundred and seventeen patients with prostate adenocarcinoma and 183 population-based controls were recruited to this case-control study. Genotyping of the GSTP1 (Ile105Val), GSTM1 (null), GSTT1 (null) and CYP1A1 (Ile462Val) genes was performed using polymerase chain reaction (PCR) based techniques on DNA prepared from peripheral blood. A questionnaire was used to collect demographic information from each subject. Cases were significantly older (P<0.0001) and had significantly greater family history of prostate cancer (P<0.0001), confirming known risk factors for this disease. By chi(2) analysis, none of the genotype distributions varied among cases and controls. Using a logistic regression model to control for known risk factors we were also unable to demonstrate a significant association with prostate cancer for any of the polymorphisms tested. This population fails to identify a relationship between the above polymorphisms and prostate adenocarcinoma.     

Genetic polymorphism of glutathione S-transferase genes (GSTM1, GSTT1 and GSTP1) and susceptibility to prostate cancer in Northern India

OBJECTIVE: To examine the association of glutathione-S-transferase (GST) gene polymorphisms in patients with sporadic prostate cancer, in a North Indian population, as GSTs are active in detoxifying a wide variety of endogenous or exogenous carcinogens, and genetic polymorphisms of GSTM1, GSTT1 and GSTP1 have been assessed to evaluate the relative risk of various cancers. PATIENTS AND METHODS: We assessed 127 patients with prostate cancer and 144 age-matched controls, all from North India. The GSTT1 and GSTM1 null genotypes were identified by multiplex polymerase chain reaction (PCR) in peripheral blood DNA samples, and GSTP1-313 A/G polymorphism was determined by PCR/restriction fragment length polymorphism. RESULTS: There was a significant association in null alleles of the GSTM1 (odds ratio 2.239, 95% confidence interval 1.37-3.65, P = 0.001) and GSTT1 (1.891, 1.089-3.282, P = 0.026) with prostate cancer risk, and in the -313 G alleles (Val) of the GSTP1 gene (2.48, 1.51-4.08, P < 0.001). The combined analysis of these three genotypes showed a further increase in the risks of prostate cancer (7.23, 2.42-22.6, P < 0.001). CONCLUSION: The GSTP1-313 G polymorphism, and null alleles of GSTM1 and GSTT1, are strong predisposing risk factors for sporadic prostate cancer in North India.     

Association of HER-2 polymorphism with Japanese sporadic prostate cancer susceptibility

BACKGROUND: Genetic polymorphisms may affect the development of prostate cancer (Pca). HER-2 is a proto-oncogene that has an important role in many human cancers, including Pca. To determine the association of the HER-2 gene with Japanese sporadic Pca, we analyzed the frequency of codon 655 (A/G, isoleucine, or valine) in case and control group. METHODS: We genotyped Ile 655 Val in Pca patients (n = 285) and in matched controls (n = 233). Statistical analyses were performed by Fisher's exact test and logistic regression analysis. RESULTS: We observed a significantly lower frequency of the Val655 allele in the Pca patients (14.7%) compared to the control group (26.2%) (P = 0.0025, odds ratio (OR) = 0.476, 95% CI = 0.306-0.740). This SNP was not found to be correlated with clinical stage, PSA level, Gleason score of biopsies or age at diagnosis. CONCLUSIONS: Our results indicate that the frequency of Val655 in HER-2 was significantly lower in Japanese Pca patients, however, it was recently reported that Val655 was significant higher in breast cancer patients. This contradictory observation in prostate and breast cancer patients is interesting considering the opposite hormonal sensitivity of these two cancers.     

Genetic polymorphisms in head and neck cancer risk

OBJECTIVE: To assess whether genetic polymorphisms implicated as risk factors for other tobacco-associated malignancies are associated with altered risk of head and neck squamous cell carcinoma. DESIGN: Case-control study. SUBJECTS: One hundred sixty patients with head and neck squamous cell carcinoma recruited from a university-based head and neck oncology clinic and 149 population-based controls. METHODS: Genotyping of the CYP1A1 (Ile462Val), GSTM1 (null), GSTP1 (Ile105Val), GSTT1 (null), and P53 (Arg72Pro) genes was performed by polymerase chain reaction-based techniques on DNA prepared from peripheral blood. In addition, a questionnaire was used to collect demographic information from each subject. RESULTS: Cases were significantly older (p <.0001) and had significantly greater tobacco use (p <.0001) and were more likely to be male (p <.0001) than were control subjects, thus confirming known risk factors for this disease. When cases and controls were compared by simple chi-square analysis, only the frequency of CYP1A1 (Ile462Val) polymorphism was significantly different between cases and controls (OR =.42; 95% CI =.18-.99; p <.04). However, with a logistic regression model to control for known risk factors, we were unable to demonstrate a significant association with head and neck cancer for any of the polymorphisms tested, including CYP1A1. CONCLUSIONS: This population fails to identify a relationship between the above-mentioned polymorphisms and head and neck cancer.     

CYP1A2基因多态性与前列腺癌的相关性研究

目的:评价CYP1A2基因单核苷酸多态性(SNPs)与前列腺癌分期分级的相关性。方法:对253例良性前列腺增生(BPH)患者与206例去势前列腺癌患者CYP1A2基因中rs2069514-3859(A>G)位点及rs2069525-1707(C>T)位点进行基因测序,并对各基因表型与前列腺癌的分期分级相关性进行统计学分析。结果:BPH及去势前列腺癌患者的两种CYP1A2单核苷酸多态性的发生率无明显差异(P>0.05),其基因多态性与前列腺癌的病理分期均无相关性(P>0.05);但rs2069525-1707(C>T)中含C等位基因型的前列腺癌Gleason评分多在7分以下(P=0.030,OR=4.658,95%CI:1.222～17.754)。结论:CYP1A2基因的SNPs与前列腺癌的病理分级之间可能有一定的相关性,但其发生机制及临床意义有待进一步证实及研究。     

New chemolysis for urological calcium phosphate calculi – a study in vitro

Background

N-acetyltransferase 2 is phase II metabolizing enzyme that participates in the bioconversion of heterocyclic arylamines into electrophilic nitrenium ions, which are important ultimate carcinogens that are directly implicated in tumor initiation process. This study was conducted to examine; (1) whether the N-acetyltransferase 2 (NAT2) genotype is a risk factor for prostate cancer, (2) to study effect of NAT2 genotype on modifying prostate cancer risk from tobacco use.

Methods

The case control study was undertaken over a period of 28 months and included 130 prostate cancer patients (CaP) and 140 controls. The NAT2 genotypes were identified by PCR-RFLP method in DNA extracted from peripheral blood. Genotype frequencies and the association of genotypes with patients and control groups were assessed by logistic regression model.

Results

We observed non-significant association of rapid acetylator genotype NAT2 (OR = 1.452, 95% CI: 0.54–1.87, P = 0.136) in prostate cancer patients. However significant association was observed between rapid acetylator genotype NAT2 and CaP tobacco users (OR = 3.43, 95% CI: 1.68–7.02, P-value < 0.001) when compared with controls.

Conclusion

The data suggests that the NAT2 rapid acetylator genotypes may play an important role in determining the risk of developing prostate cancer particularly in the tobacco users of north Indian population.     

Glutathione S-transferase gene polymorphisms (GSTM1, GSTT1, GSTP1) and prostate cancer: a case-control study in Tehran, Iran

We evaluated the relationship between polymorphisms in the glutathione S-transferases (GSTs) GSTM1, GSTT1 and GSTP1 genes and prostate cancer (PCa). PCR-restriction fragment length polymorphism assay was used to genotype the GSTM1, GSTT1, and GSTP1 polymorphisms in 168 PCa cases and 336 frequency matched controls. The GSTM1 null, and GSTT1 null genotypes were associated with an increased odds ratio (OR) for PCa (OR=3.28, 95% confidence interval (CI): 2.47-5.64; P=0.005, and OR=3.21, 95% CI: 2.52-5.64; P=0.005, respectively) (Pcorrected=0.0062). The frequency of GSTP1 Val/Val genotype was 14.3% in cases compared with 2.4% in controls, this polymorphism thus being associated with a significantly increased risk of PCa (OR=3.72, 95% CI: 1.67-5.65; P=0.002). The risk associated with the concurrent absence of both of the genes (OR=4.8, 95% CI: 2.34-6.78) was greater than the product of risk in men with either null (OR=1.52, 95% CI: 0.82-2.31) genotype combinations (P=0.001, Pcorrected=0.0045). The combination of GSTP1 Ile/Val or Val/Val polymorphism with the GSTT1 null and GSTM1 null type resulted in an OR of 6.21 (95% CI: 4.83-16.87) (P=0.0001, Pcorrected=0.0062). A higher frequency of the GSTM1 null genotype and GSTT1 null genotype was observed in patients with Gleason score >7, with an OR for GSTM1 null 4.67 (95% CI: 3.64-7.62; P=0.001) and with an OR for GSTT1 null 3.62 (95% CI: 2.31-5.74; P=0.004). The results obtained demonstrated that simultaneous presence of three potentially risk alleles (GSTM1 null, GSTT1 null and GSTP1 Val) lead to a significant OR increase for PCa.