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基因多态性与各种肿瘤的关系.doc

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1、2003 年Kripp l等 1 报道VEGF 936 C等位基因携带者患乳腺癌的危险性降低,1 Kripp l P, LangsenlehnerU, RennerW, et al. A common 936 C /Tgene polymorphism of vascular endothelial growth factor is associatedwith decreased breast cancer risk. Int J Cancer, 2003, 106: 4682471.我们进行了一系列的生长因子基因多态性与结直肠癌关系的研究,已经发现VEGF 61 G/G基因型和G等位基因与

2、结直肠癌的发生有关 9 。VEGF936 T/C 基因多态性与结直肠癌关系的研究表明VEGF 936 C /C基因型或936 C等位基因与结直肠癌的生成无关,但有助于减少术后结肠吻合口瘘的发生。含有VEGF 936 T基因的结直肠癌患者术后并发吻合口瘘的机会增加,或许VEGF 936 T 基因可作为检测结直肠癌或预测结直肠癌术后并发吻合口瘘的一个危险因素,但这需要进一步的研究。同时观察这一基因多态性在其他伤口愈合并发症中的作用也将很有意义。血管内皮生长因子936 T/C基因多态性与结直肠癌及术后吻合口瘘的关系吴国洋 王效民 Michael Keese Till Hasenberg J rgW.

3、 Sturm血管内皮生长因子基因多态性与肺癌危险度的关系Lee SJ , Lee SY, Jeon HS, et al/ / Cancer Ep idemiol Biomarkers Prev, 2005, 14: 571 - 575背景和目的:血管生成是包括肺癌在内的恶性肿瘤发生、发展和转移中的一个重要过程。血管内皮生长因子基因( vascular endothelial growth factor, VEGF)变异可以导致其编码蛋白的产量和活性的改变,通过作用于肿瘤的血管生成过程,从而引发个体对肺癌易感性的差异。为了检验这一假设,作者研究了韩国人VEGF基因的3个单核苷酸多态性( - 46

4、0T C、+ 405C G和936C T)及其单倍型和肺癌危险度之间的关系。方法:研究对象包括432名肺癌患者和432名年龄和性别匹配的对照。运用贝叶斯定理构建单体型。采用logistic回归校正相关协变量计算 OR值。结果:在+ 405位点,与CC 和CG基因型比较 , GG基因型个体小细胞肺癌危险度显著降低,调整OR 值为0136, 95%可信限为01 17 0178; 936位点变异基因型 (CT和CT + TT)个体较野生基因型(CC)个体小细胞肺癌的危险度降低,调整OR值分别为0147和0 144, 95%可信限分别为01 260185和01240180。CGT 单体型与小细胞肺癌的

5、危险度降低相关 ,调整OR 值为0139, 95% 可信限为01180187;而TCC 与小细胞肺癌的危险度增加相关,调整OR 值为1163, 95%可信限为11 1421 33。上述多态性对小细胞肺癌以外的肺癌类型的危险度没有影响。单体型TCT和TGT与整体肺癌危险度相关,调整OR值分别为0138和3194, 95% 可信限分别为01250160和21007176, TCT和TGT单体型的这种作用在3种主要的肺癌组织类型中均有发现。结论: VEGF基因多态性与个体肺癌遗传易感性有关。(冷曙光)Objectives: Vascular endothelial growth factor (VE

6、GF) is a potent stimulus of angiogenesis that has an important role in many humanmalignancies including prostate carcinoma (PCa). We evaluated the role of the functional VEGF polymorphisms as genetic markers forPCa susceptibility and prognosis. Methods: The study included 101 patients with PCa and t

7、he 100 age-matched healthy men. The VEGFgenotypes _1154G A were identified by allele-specific polymerase chain reaction (AS-PCR) and the genotypes _634G C and936C T were identified by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Results: A negativeassociation was fo

8、und between VEGF _1154AA genotype and PCa risk (OR = 0.27; P = 0.009). Furthermore, the presence of theVEGF _1154A allele appeared to be associated with an increased risk of higher tumor grade (OR = 0.37; P = 0.01). A significantincreased risk of prostate cancer was associated with the VEGF _634 (GC

9、 + CC) combined genotype (OR = 1.95; P = 0.02). The VEGF_634C allele was associated with the aggressive phenotype of prostate cancer as defined by the high histological grade (OR = 3.48;P = 0.007). The VEGF _1154A/_634G haplotype was negatively associated with PCa risk (OR = 0.48; P = 0.005) and hig

10、h tumorgrade compared to low grade (OR = 0.37; P = 0.02). Conclusions: Genetic variations in the VEGF may predict not only PCa riskbut also tumor aggressiveness.Association of VEGF genetic polymorphisms with prostatecarcinoma risk and clinical outcomeSana Sfar a,*, Elham Hassen a, Hamadi Saad b, Fao

11、uzi Mosbah c, Lotfi Chouchane aa Laboratoire dImmuno-Oncologie Moleculaire, Faculte de Medecine de Monastir, Universite de Monastir, Tunisiab Service dUrologie, Hopital Universitaire Fattouma Bourguiba, Monastir, Tunisiac Service dUrologie, Hopital Universitaire Sahloul, Sousse, TunisiaReceived 1 Fe

12、bruary 2006; received in revised form 7 June 2006; accepted 2 July 2006Abbreviations used: PCa, prostate carcinoma; VEGF, vascular endothelialgrowth factor; DC, dendritic cells; NF-jB, nuclear factor-jB; SNP,single nucleotide polymorphism; PSA, prostate-specific antigen; RFLPPCR,restriction fragment

13、 length polymorphism PCR; AS-PCR, allelespecific PCR; OR, odds ratio.Associations of Single Nucleotide Polymorphisms inthe Vascular Endothelial Growth Factor Gene with theCharacteristics and Prognosis of Renal Cell CarcinomasYoshihisa Kawai, Shigeru Sakano, Yoshihito Korenaga, Satoshi Eguchi, Katsus

14、uke Naito *Department of Urology, Yamaguchi University School of Medicine, Yamaguchi, JapanObjectives: Vascular endothelial growth factor (VEGF) is considered to playcritical roles in tumor development and progression, especially in renal cellcarcinoma (RCC) via von Hippel-Lindau gene inactivation.

15、Although VEGF_2578CC, _1154GG, and _634CC genotypes are reportedly correlated withhigher levels of VEGF production, no previous studies have reported on theassociations of these polymorphisms with RCCs. This study was aimed toclarify the effects of these functional polymorphisms on RCC progressionan

16、d prognosis.Methods: Weinvestigated the associations of three polymorphisms(_2578C/A, _1154G/A, and _634C/G) in the VEGF gene with the clinicopathologicparameters and survival of 213 patients with RCC. The _2578C/A and_634C/G polymorphisms were genotyped using a polymerase chain reaction(PCR) restri

17、ction fragment lengthpolymorphismtechniqueandthe_1154G/Apolymorphism was genotyped by an amplification refractory mutation systemPCR technique.Results: The GA + AA genotypes of _1154G/A were weakly associated withsmaller tumors, lower tumor stage, and lower stage grouping ( p = 0.028,p = 0.012, and

18、p = 0.028, respectively). The CA and CA + AA genotypes of_2578C/A were weakly associated with less frequent lymph node metastasis( p = 0.029 and p = 0.034, respectively) and were significantly associatedwith favorable cancer-specific survival ( p = 0.047 and p = 0.048, respectively).There was no app

19、arent clinical effect of the _634C/G polymorphism.Conclusions: These results suggest that some VEGF genotypes may haveeffects on RCC progression or prognosis, possibly through altered VEGFexpression. This finding might help in clarifying the mechanisms of RCCdevelopment and progression.5. Conclusion

20、In conclusion, our study provides evidence thatsome VEGF genotypes may have effects on RCCprogression or prognosis and that these effectsmay possibly be due to altered VEGF expressionaccording to VEGF polymorphisms. These findingsmight help toward clarifying the mechanisms ofRCC development and prog

21、ression. However, ourresults were obtained with a limited sample size andtherefore allowed us to draw just preliminaryconclusions. Functional and independent studieswith a larger number of patients are needed toconfirm our results.Archives of Medical Research 39 (2008) 209e211Genetic Polymorphism of

22、 VEGF-1154 (A/G)in Laryngeal Squamous Cell CarcinomaZeynep Nil U nal,a Murat U nal,b O zlen Tubay Ba_gdato_glu,a Gurbuz Polat,a and U_gur AtikaaDepartment of Biochemistry and bDepartment of Otorhinolaryngology, Mersin University School of Medicine, Mersin, TurkeyReceived for publication August 17, 2

23、007; accepted September 24, 2007 (ARCMED-D-07-00379).We conclude that GG genotype of the VEGF gene mayincrease the risk of laryngeal SCC in this population. VEGFgene polymorphism may be an important potential geneticand therapeutic marker of laryngeal SCC. The major limitationsof our study are the modest sample size and matchingproblem in controls and patients according to genderand age. Thus, further studies are necessary to delineatethe potential role of VEGF polymorphism in the susceptibilityto laryngeal SCC in a larger population.

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