Display options
Share it on

Genet Mol Biol. 2011 Oct;34(4):546-52. doi: 10.1590/S1415-47572011005000053. Epub 2011 Oct 01.

Polymorphisms associated with the risk of lung cancer in a healthy Mexican Mestizo population: Application of the additive model for cancer.

Genetics and molecular biology

Rebeca Pérez-Morales, Ignacio Méndez-Ramírez, Clementina Castro-Hernández, Ollin C Martínez-Ramírez, María Eugenia Gonsebatt, Julieta Rubio

Affiliations

  1. Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, México.

PMID: 22215955 PMCID: PMC3229106 DOI: 10.1590/S1415-47572011005000053

Abstract

Lung cancer is the leading cause of cancer mortality in Mexico and worldwide. In the past decade, there has been an increase in the number of lung cancer cases in young people, which suggests an important role for genetic background in the etiology of this disease. In this study, we genetically characterized 16 polymorphisms in 12 low penetrance genes (AhR, CYP1A1, CYP2E1, EPHX1, GSTM1, GSTT1, GSTPI, XRCC1, ERCC2, MGMT, CCND1 and TP53) in 382 healthy Mexican Mestizos as the first step in elucidating the genetic structure of this population and identifying high risk individuals. All of the genotypes analyzed were in Hardy-Weinberg equilibrium, but different degrees of linkage were observed for polymorphisms in the CYP1A1 and EPHX1 genes. The genetic variability of this population was distributed in six clusters that were defined based on their genetic characteristics. The use of a polygenic model to assess the additive effect of low penetrance risk alleles identified combinations of risk genotypes that could be useful in predicting a predisposition to lung cancer. Estimation of the level of genetic susceptibility showed that the individual calculated risk value (iCRV) ranged from 1 to 16, with a higher iCRV indicating a greater genetic susceptibility to lung cancer.

Keywords: Mexicans; additive model; genetic polymorphism; lung cancer; molecular epidemiology

References

  1. Nat Rev Cancer. 2010 May;10(5):353-61 - PubMed
  2. Carcinogenesis. 2002 Feb;23(2):257-64 - PubMed
  3. Thorax. 2007 Dec;62(12):1050-7 - PubMed
  4. Carcinogenesis. 1997 Apr;18(4):641-4 - PubMed
  5. Lung Cancer. 2007 Nov;58(2):184-90 - PubMed
  6. Anticancer Res. 2003 May-Jun;23(3A):2111-24 - PubMed
  7. Carcinogenesis. 2006 Mar;27(3):560-7 - PubMed
  8. Int J Biol Markers. 2008 Jan - Mar;23(1):24-30 - PubMed
  9. Carcinogenesis. 2000 Apr;21(4):551-5 - PubMed
  10. Cancer Epidemiol Biomarkers Prev. 2004 Aug;13(8):1342-8 - PubMed
  11. Nat Med. 2008 Aug;14(8):812-3 - PubMed
  12. Mutat Res. 2008 Mar 1;639(1-2):1-10 - PubMed
  13. Nat Rev Cancer. 2006 Dec;6(12):947-60 - PubMed
  14. J Natl Cancer Inst. 2009 Jan 7;101(1):24-36 - PubMed
  15. Lancet. 1997 Aug 30;350(9078):630-3 - PubMed
  16. Int J Med Sci. 2007 Feb 01;4(2):59-71 - PubMed
  17. Nat Genet. 2002 May;31(1):33-6 - PubMed
  18. Hum Biol. 2000 Dec;72(6):1039-43 - PubMed
  19. Future Oncol. 2007 Dec;3(6):617-27 - PubMed
  20. Cancer Res. 1996 Nov 1;56(21):4965-9 - PubMed
  21. Hum Mol Genet. 1994 Mar;3(3):421-8 - PubMed
  22. J Biochem. 1991 Sep;110(3):407-11 - PubMed
  23. IARC Sci Publ. 1999;(148):159-72 - PubMed
  24. Cancer Lett. 2001 Dec 10;174(1):35-44 - PubMed
  25. Toxicol Lett. 2003 Sep 15;144(1):69-76 - PubMed
  26. Carcinogenesis. 2007 Jun;28(6):1287-93 - PubMed
  27. Int J Cancer. 1997 Apr 10;71(2):192-5 - PubMed
  28. Lung Cancer. 2010 Jul;69(1):19-25 - PubMed
  29. Hum Biol. 2008 Aug;80(4):457-65 - PubMed
  30. Nat Rev Cancer. 2001 Oct;1(1):82-6 - PubMed
  31. Cancer Epidemiol Biomarkers Prev. 1998 Mar;7(3):215-9 - PubMed
  32. Cancer Lett. 2000 Oct 16;159(1):63-71 - PubMed
  33. Cancer Epidemiol Biomarkers Prev. 2007 Dec;16(12):2736-44 - PubMed
  34. JAMA. 2008 May 28;299(20):2423-36 - PubMed
  35. Pharmacogenet Genomics. 2005 Aug;15(8):571-8 - PubMed
  36. Cancer Epidemiol Biomarkers Prev. 2008 May;17(5):1120-6 - PubMed
  37. Carcinogenesis. 2008 Oct;29(10):1938-43 - PubMed
  38. Carcinogenesis. 2003 May;24(5):875-82 - PubMed
  39. Cancer Epidemiol Biomarkers Prev. 2002 Jan;11(1):15-21 - PubMed
  40. Lung Cancer. 2008 Apr;60(1):40-46 - PubMed
  41. Cancer Epidemiol Biomarkers Prev. 2006 Apr;15(4):624-9 - PubMed
  42. Cancer Lett. 1996 Oct 22;107(2):229-33 - PubMed
  43. Biomarkers. 2008 May;13(3):282-95 - PubMed
  44. Carcinogenesis. 1998 May;19(5):813-7 - PubMed
  45. Cancer Lett. 2006 Jun 8;237(1):102-8 - PubMed

Publication Types