p16INK4a polymorphism: associations with tumour progression in patients with sporadic colorectal cancer

  • Authors:
    • Jonathan M. McCloud
    • Rangasamy Sivakumar
    • Alex Greenhough
    • Jackie Elder
    • Peter W. Jones
    • Mark Deakin
    • James B. Elder
    • Anthony A. Fryer
    • Paul R. Hoban
  • View Affiliations

  • Published online on: November 1, 2004     https://doi.org/10.3892/ijo.25.5.1447
  • Pages: 1447-1452
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Abstract

Deregulated tumour expression of p16INK4a has previously been described in association with clinical progression in sporadic colorectal cancer patients (CRC). Furthermore, p16INK4a promoter hypermethylation leading to gene silencing has been shown to occur in advanced colorectal tumours and has been associated with patient survival. p16INK4a is polymorphic, with variant alleles being associated with tumour progression in melanoma. In this study we have examined p16INK4a polymorphism as a marker of tumour progression in sporadic CRC. Polymorphic sites G/A442, C/G500, and C/T540, were studied, these alleles obeyed Hardy Weinberg equilibrium in a control group, but not in the CRC cases. G/A442 and CG500 alleles were in linkage disequilibrium in both cases and controls. In controls the C/T540 alleles demonstrated no linkage with either other site, whilst an association was demonstrated between C/G500 and C/T540 alleles in the cases (p=0.011). Furthermore, the distribution of C/T540 genotypes was different between the groups (p=0.002). Within the CRC cases, patients with the GG442 genotype were more commonly associated with decreased tumour differentiation (p=0.018), advancing Dukes' stage (p=0.006) and T-stage (p=0.007) than patients with the GA442 and AA442 genotypes. Patients with the CC500 genotype were more commonly associated with decreased tumour differentiation (p=0.012), advancing Dukes' stage (p=0.015), and N-stage (p=0.031). No associations between patient C/T540 genotype and clinical prognostic parameters were found. An analysis of patient tumour expression with p16INK4a genotype revealed patients with the CC500 genotype were more commonly associated with reduced tumour p16 expression (p=0.046). In summary our data indicate that p16INK4a polymorphism is associated with tumour progression in patients with sporadic CRC.

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November 2004
Volume 25 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
McCloud JM, Sivakumar R, Greenhough A, Elder J, Jones PW, Deakin M, Elder JB, Fryer AA and Hoban PR: p16INK4a polymorphism: associations with tumour progression in patients with sporadic colorectal cancer. Int J Oncol 25: 1447-1452, 2004
APA
McCloud, J.M., Sivakumar, R., Greenhough, A., Elder, J., Jones, P.W., Deakin, M. ... Hoban, P.R. (2004). p16INK4a polymorphism: associations with tumour progression in patients with sporadic colorectal cancer. International Journal of Oncology, 25, 1447-1452. https://doi.org/10.3892/ijo.25.5.1447
MLA
McCloud, J. M., Sivakumar, R., Greenhough, A., Elder, J., Jones, P. W., Deakin, M., Elder, J. B., Fryer, A. A., Hoban, P. R."p16INK4a polymorphism: associations with tumour progression in patients with sporadic colorectal cancer". International Journal of Oncology 25.5 (2004): 1447-1452.
Chicago
McCloud, J. M., Sivakumar, R., Greenhough, A., Elder, J., Jones, P. W., Deakin, M., Elder, J. B., Fryer, A. A., Hoban, P. R."p16INK4a polymorphism: associations with tumour progression in patients with sporadic colorectal cancer". International Journal of Oncology 25, no. 5 (2004): 1447-1452. https://doi.org/10.3892/ijo.25.5.1447