PlA polymorphism of GP3A gene is a new prognostic factor of renal cancer
https://doi.org/10.17650/1726-9776-2007-3-3-27-31
Abstract
Introduction & Objectives. Cell adhesion molecules play an important role in the pathogenesis of renal cell carcinoma (RCC). Glycoprotein IIIa gene (gp3A) encodes the beta chain of integrin receptor and contains Pl1llA (Leu33Pro) polymorphism. The authors have earlier investigated a role of GP3A polymorphism in prostate cancer and determined that the PlA2 polymorphism of gp3A gene increased the risk of prostate cancer development and invasion. The aim of the study was to examine an association of PlA polymorphism with sporadic RCC patients in the Moscow region.
Material and methods. We determined the genotype of gp3A of 100 patients with RCC and 30 age-matched controls, by using polymerase chain reaction was used.
Results. The distribution of PlA polymorphism in the Moscow population was 76% of PlA1/A1 allele, 22% of PlA1/A2 allele and 2% of PlA2/A2 allele. Sixty (60%) patients with RCC had PlA1/A1 allele, 33 (33%) had PlA1/ A2 allele and 4 (4%) had PlA2/A2 allele. The frequency of PlA1/A2 allele was significantly higher in RCC patients (33%) than in the population (22%) (p < 0,02). Analyzing the genotype subject to TNM stage in patients with localized cancer (T1—2N0M), allele PlA1/A1 was determined in 27 (60%), PlA1/A2 in 15 (35,6%), and PLA1/A2 in 2 (4,4%). Among the patients with invasive cancer (T3—4N0—2M0), 23 (82,1%) and 5 (17,9%) had PLA1/A1 allele and PLA1/A2, respectively. Also, 13 (48%) patients of those with metastatic cancer had PLA1/A1; 12 (44,5%) and 2 (7,5%) had PLA1/A2 and PLA2/A2 alleles, respectively. As for the metastatic group, the frequency of PlA1/A2 genotype was significantly higher (44,5%) than that in the population (22%) (p = 0,02). The OR RCC development for PLA1/A2 genotype as compared to PlA1/A1 was 2,1 for localized cancer and 3,17 for the metastatic group.
Conclusions. PlA2 polymorphism of gp3A gene increases the risk of RCC and metastasis. The course of RCC in patients carrying PlA2 polymorphism is characterized by a more rapid metastatic progression. Comparison of the results of the invasive and metastatic groups can lead to some conclusions. PlA2 polymorphism may be of more considerable importance in metastatic processes than in the development of RCC. The determination of PlA polymorphism seems to be a new predictor of RCC and it is useful and suitable for screening of high-risk patients.
About the Authors
O. B. Loran
Russian Medical Academy of Postgraduate Education
Russian Federation
Russian Federation
Urology Department
MoscowA. V. Seregin
Russian Medical Academy of Postgraduate Education
Russian Federation
Russian Federation
Urology Department
MoscowG. I. Myandina
Russian Medical Academy of Postgraduate Education
Russian Federation
Russian Federation
Urology Department
MoscowK. Yu. Kashintsev
Russian Medical Academy of Postgraduate Education
Russian Federation
Russian Federation
Urology Department
MoscowN. A. Shustitsky
Russian Medical Academy of Postgraduate Education
Russian Federation
Russian Federation
Urology Department
MoscowA. A. Seregin
Russian Medical Academy of Postgraduate Education
Russian Federation
Russian Federation
Urology Department
MoscowReferences
1. Аксель Е.М. Заболеваемость злокачественными новообразованиями мочевых и мужских половых органов в России в 2003 г. Онкоурология 2005;(1):6—9.
2. Atkins M.B., Avigan D.E., Bukowski R.M. et al. Innovations and challenges in renal cancer: consensus statement from the first international conference. Clin Cancer Res 2004;10(18 Pt 2):6277S—81S.
3. Linehan W.M., Zbar. B. Focus on kidney cancer. Cancer Cell 2004;6(3):223—8.
4. Atkins М.B., Regan M., McDermott D. Update on the role of interleukin 2 and other cytokines in the treatment of patients with stage IV renal carcinoma. Clin Cancer Res 2004;10(18 Pt 2):6342S—6S.
5. Potter C., Harris A.L. Hypoxia inducible carbonic anhydrase IX, marker of tumor hypoxia, survial pathway and therapy target. Cell Cycle 2004;3:164—7.
6. Bamias A., Chorti M., Deliveliotis C. et al. Prognostic significanсe of CA 125, CD 44 and epithelial membrane antigen in renal cell carcinoma. Urology 2003;62(2):368—73.
7. Kim H.L., Stligson D., Liu X. et al. Using tumor markers to predict the survival of patients with metastatic renal cell carcinoma. J Urol 2005;173(5):1496—501.
8. Syrigos K.N., Harrington K.J., Pignatelli M. et al. Role of adhesion molecules in bladder cancer: an important part of the jigsaw. Urology 1999;53(2):428—34.
9. Takeichi M. Cadherin cell adhesion receptors as a morphogenetic regulator. Science 1991;22(251):1451—5.
10. Bojesen S.E., Tybjaerg-Hansen A., Nordestgaard B.G. Integrin 3 Leu33Pro homozygosity and risk of cancer. J Natl Cancer Inst 2003;95:1150—7.
11. Серегин А.А. Клиническое значение аллельного распределения гена GP3A при раке предстательной железы. Автореф. дис. … канд. мед наук. М.; 2005.
12. Staehler M., Rohrman K., Haseke N., Stief C.G. Targeted agents for the treatment of advanced renal cell carcinoma. Curr Drug Targets 2005;6(7):835—46.
13. Huber W., Boer J.M., von Heydeberck A. et al. Transcription profiling of renal cell carcinoma. Verh Dtsch Ges Pathol 2002;86:153—64.
14. Wechsel H.W., Petri E., Feil G. et al. Renal cell carcinoma: immunohistological investigation of expression of the integrin alpha v beta 3. Anticancer Res 1999;19(2C):1529—32.
Review
For citations:
Loran O.B., Seregin A.V., Myandina G.I., Kashintsev K.Yu., Shustitsky N.A., Seregin A.A. PlA polymorphism of GP3A gene is a new prognostic factor of renal cancer. Cancer Urology. 2007;3(3):27-31. (In Russ.) https://doi.org/10.17650/1726-9776-2007-3-3-27-31
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