Association of single nucleotide polymorphisms in cell cycle regulatory genes with oral cancer susceptibility

Br J Oral Maxillofac Surg. 2014 Sep;52(7):652-8. doi: 10.1016/j.bjoms.2014.05.010. Epub 2014 Jun 16.

Abstract

Alterations in the regulation of the cell cycle are strongly linked to tumorigenesis, so genetic variants in genes critical to control of the cycle are good candidates to have their association with susceptibility to oral cancer assessed. In this hospital-based, case-control study of 445 patients who had been newly-diagnosed with oral cancer and 449 unaffected controls, we used a multigenic approach to examine the associations among a panel of 10 selected polymorphisms in the pathway of the cell cycle that were possibly susceptible to oral cancer. Six of 9 single nucleotide polymorphisms in the cell cycle showed significant risks for oral cancer, the highest risk being evident for p27 (rs34329; Odds ratio 3.05, 95% CI 2.12 to 4.40). A significant risk of oral cancer was also evident for individual polymorphisms of cyclin E (rs1406), cyclin H (rs3093816), cyclin D1-1 (rs647451), cyclin D2 (rs3217901) and Rb1-2 (rs3092904). The risk of oral cancer increased significantly as the number of unfavourable genotypes in the pathway increased, and so the results point to a stronger combined effect of polymorphisms in important cell cycle regulatory genes on predisposition to oral cancer.

Keywords: Cell cycle; Oral cancer; Single nucleotide polymorphism; Susceptibility.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / genetics*
  • Case-Control Studies
  • Cyclin D1 / genetics
  • Cyclin D2 / genetics
  • Cyclin D3 / genetics
  • Cyclin E / genetics
  • Cyclin H / genetics
  • Cyclin-Dependent Kinase 5 / genetics
  • Cyclin-Dependent Kinase Inhibitor p27 / genetics
  • Female
  • Follow-Up Studies
  • Genes, cdc / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Genetic Variation / genetics
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mouth Neoplasms / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Retinoblastoma Protein / genetics
  • Retinoblastoma-Like Protein p130 / genetics
  • Retrospective Studies
  • Young Adult

Substances

  • CCND1 protein, human
  • CCND2 protein, human
  • CCND3 protein, human
  • CCNH protein, human
  • Cyclin D2
  • Cyclin D3
  • Cyclin E
  • Cyclin H
  • RBL2 protein, human
  • Retinoblastoma Protein
  • Retinoblastoma-Like Protein p130
  • Cyclin D1
  • Cyclin-Dependent Kinase Inhibitor p27
  • Cyclin-Dependent Kinase 5
  • CDK5 protein, human