Gallegos-Arreola MP, Peralta-Leal V, Morgan-Villela G, Puebla-Pérez AM

Idioma: Español
Referencias bibliográficas: 36
Paginas: 21-30
Archivo PDF: 175.45 Kb.

RESUMEN

La enzima timidilato sintasa (TYMS) convierte dUMP a dTMP y participa en la regulación de nucleótidos requeridos para la síntesis del DNA. También interviene en el metabolismo del 5-fluorouracilo, el agente quimioterapéutico más utilizado en el tratamiento de cáncer colorrectal (CCR). Se diseñó un estudio de casos y controles para investigar la frecuencia del polimorfismo TS 1494del6 en el gen TYMS en pacientes con CCR de la población mexicana. El estudio consistió en 253 pacientes con CCR y 200 controles de la población general del Occidente de México. Se determinó la frecuencia del polimorfismo y su asociación con edad, género, estadio y metástasis por medio de razón de momios (95% IC). El genotipo 6pb-/6pb- en pacientes con CCR fue de 18% (45/253) y en controles de 11% (22/200) con una razón de momios de 1.8 (1-4) p = 0.059. Al estratificar los grupos de estudio por edad (‹ 50 años), sexo masculino, estadio III-IV y presencia de metástasis el genotipo 6pb-/6pb fue de riesgo (p ‹ 0.05). El genotipo 6pb-/6pb que se encuentra en la región no transcrita del extremo 3´ del gen TYMS en la muestra analizada participa de manera importante en el desarrollo de CCR de la población mexicana.

REFERENCIAS (EN ESTE ARTÍCULO)

1. Mohar A, Frias-Mendivil M, Suchil-Bernal L, et al. Descriptive epidemiology cancer in the National Cancer Institute of Mexico. Salud Pública Mex 1997; 39: 253-358.

2. http://www.ssa.gob.mx. Secretaría de Salud México. Fecha de último acceso: agosto de 2007.

3. http://www.ssj.gob.mx. Secretaría de Salud Jalisco. Registro estatal de cáncer en Jalisco. Fecha de último acceso: agosto de 2007.

4. Kim SA, Lee JH, Park SY, et al. Depressed-type of early colon cancer with extensive lymph node metastasis. Yonsei Med J 2007; 48: 135-8.

5. Kyoung-Jin S, Croxford R, Yates Z, et al. Effect of the methylenetetrahydrofolate Reductase C677T Polymorphism on Chemosensitivity of Colon and Breast Cancer Cells to 5-Fluorouracil and Methotrexate. J Natl Cancer Inst 2004; 96: 134- 44.

6. Kralovanszky J, Adleff V, Hitre E, et al. Pharmacogenetic studies on the prediction of efficacy and toxicity of fluoropyrimidine- based adjuvant therapy in colorectal cancer. Magy Onkol 2007; 51: 113-25.

7. Spindler KL, Nielsen JN, Lindebjerg J, Jakobsen A. Germline Polymorphisms may Act as Predictors of Response to Preoperative Chemoradiation in Locally Advanced T3 Rectal Tumors. Dis Colon Rectum 2007 (en prensa).

8. Hitre E, Budai B, Adleff V, et al. Influence of thymidylate synthase gene polymorphisms on the survival of colorectal cancer patients receiving adjuvant 5-fluorouracil. Pharmacogenet Genomics 2005; 15: 723-30.

9. Dotor E, Cuatrecases M, Martinez-Inesita M, et al. Tumor thymidylate synthase 1494del6 genotype as a prognostic factor in colorectal cancer patients receiving fluorouracil-based adjuvant treatment. J Clin Oncol 2006; 10: 1603-11.

10. Tsuji T, Hidaka S, Nakagoe T, et al. Polymorphism in the Thymidylate Synthase Promoter Enhancer Region. Is Not an Efficacious Marker for Tumor Sensitivity to 5-Fluorouracil-based Oral Adjuvant Chemotherapy in Colorectal Cancer? Clin Can Res 2003; 9: 3700-04.

11. Sharp L, Little J. Polymorphisms in Genes Involved in Folate Metabolism and Colorectal Neoplasia: A HuGE Review. Am J Epidemiol 2004; 159: 423-43.

12. Uchida K, Hayashi K, Kawakami K, et al. Loss of heterozygosity at the thymidylate synthase (TS) locus on chromosome 18 affects tumor response and survival in individuals heterozygous for a 28-bp polymorphism in the TS gene. Clin Cancer Res 2004; 10: 433-9.

13. Ulrich CM, Bigler J, Velicer CM, et al. Searching expressed sequence tag databases: discovery and confirmation of a common polymorphism in the thymidylate synthase gene. Cancer Epidemiol Biomarkers Prev 2000; 9: 1381-5.

14. Lenz HJ, Zhang W, Zhahedy S, et al. A 6 base-pair deletion in the 30UTR of the thymidylate synthase (TS) gene predicts TS mRNA expression in colorectal tumors. A possible candidate gene for colorectal cancer risk. Proc Am Assoc Cancer Res 2002; 43: 660.

15. Ulrich CM, Bigler J, Bostick R, et al. Thymidylate synthase promoter polymorphism, interaction with folate intake and risk of colorectal adenomas. Cancer Res 2002; 62: 3361-4.

16. Mandola MV, Stoehlmacher J, Zhang W, et al. A 6 bp polymorphism in the thymidylate synthase gene causes message instability and is associated with decreased intratumoral TS RNAm levels. Pharmacogenetic 2004; 14: 319-27.

17. Chen J, Hunter DJ, Stampfer MJ, et al. Polymorphism in the Thymidylate Synthase Promoter Enhancer RegionModifies the Risk and Survival of Colorectal Cancer. Cancer Epidemiol Biomarkers Prev 2003; 12: 958-62.

18. Ulrich CM, Curtin K, Potter JD. Polymorphisms in the Reduced Folate Carrier, Thymidylate Synthase, or Methionine Synthase and Risk of Colon Cancer. Cancer Epidemiol Biomarkers Prev 2005; 11: 2509-16.

19. Zhai X, Gao J, Hu Z, et al. Polymorphisms in thymidylate synthase gene and susceptibility to breast cancer in a Chinese population: a case-control analysis. BMC Cancer 2006; 6: 138.

20. Shi Q, Zhang Z, Neumann A, et al. Case—control analysis of thymidylate synthase polymorphisms and risk of lung cancer. Carcinogenesis 2005; 26: 649-56.

21. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215.

22. Sanguinetti CJ, Dias Neto E, Simpson AJ. Rapid silver staining and recovery of PCR products separated on polyacrylamide gels. Biotechniques 1994; 17: 914-21.

23. Konings EJ, Goldbohm RA, Brants HA, Saris WH, van den Brandt PA. Intake of dietary folate vitamers and risk of colorectal carcinoma: results from The Netherlands Cohort Study. Cancer 2002; 95: 1421-33.

24. Su LJ, Arab L. Nutritional status of folate and colon cancer risk: evidence from NHANES I epidemiologic follow-up study. Ann Epidemiol 2001; 11: 65-72.

25. Colorectal cancer. http://www.cchealth.org/health_data/ hospital_council_2007. Fecha de ultimo acceso: agosto de 2007.

26. Jemal A, Siegel R, Ward E, et al. Cancer statistics 2007. CA Cancer J Clin 2007; 57: 43-66.

27. Parkin DM, Whelan SL, Ferlay J, Teppo L, Thomas DB (eds.). World Health Organization. Cancer incidence in five continents. Vol. VIII. IARC, Scientific Publications Nº 155 (2002).

28. Alonso A, Moreno S, Valiente A, et al. Genetics mechanisms in the hereditary predisposition to colorectal cancer. Anales Sis San Navarra 2006; 26: 59-76.

29. Duran O, Gonzalez O, Cisneros L, et al. Experience in the management of colorectal cancer in the Centro Medico Nacional de Occidente (Nacional Medical Center of the West). Cir Gen 2000; 22: 153-8.

30. Hendon S, DiPalma J. US Practices for colon cancer screening. Keio J Med 2005; 54: 179-83.

31. Lynch H, Chapelle A. Hereditary colorectal cancer. N Engl J Med 2003; 348: 919-32.

32. Kumar V, Abul K, Nelson F. Patología estructural y funcional. 7a Ed. España: Ed Elsevier; 2005. Acceso en línea.

33. Zhang J, Cui Y, Luang G, et al. Association of the thymidylate synthase polymorphisms with esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma. Carcinogenesis 2004; 25: 2479-85.

34. Surgbarker P. Carcinoma of the colon. Prognosis and operative choice. Curr Prob Surg 1998; 28: 754-826.

35. Han C, Sheen SM. Obstruction and perforation in colorectal adenocarcinoma: An analysis of prognosis and current trends. Surgery 2000; 127: 370-6.

36. Aschele C, Debernardis D, Tunesi G, et al. Thymidylate synthase protein expression in primary colorectal cancer compared with the corresponding distant metastases and relationship with the clinical response to 5-fluorouracil. Clin Cancer Res 2000; 6: 4797-802.