Association between Aurora-A kinase polymorphisms and age of onset of hereditary nonpolyposis colorectal cancer in a Caucasian population

Mol Carcinog. 2007 Apr;46(4):249-56. doi: 10.1002/mc.20283.

Abstract

Aurora-A kinase is considered a potential cancer susceptibility gene that encodes a centrosome-associated, cell cycle-regulated serine/threonine kinase. We studied two single nucleotide polymorphisms (SNP) in the coding region of Aurora-A, 91T-to-A (F31I) and 169G-to-A (V57I). We studied the influence of these two polymorphisms on age of onset of hereditary nonpolyposis colorectal cancer (HNPCC). Genotyping of the Aurora-A polymorphisms was carried out on 125 Caucasian with mismatch repair (MMR) gene mutations with real-time pyrophosphate DNA sequencing. For the 91T-to-A polymorphism, we found that patients with HNPCC who were homozygous for the wild-type allele developed colorectal cancer (CRC) 7 years earlier than patients who were homozygous or heterozygous for the mutant allele. The169G-to-A polymorphism did not have a significant influence on risk for HNPCC. However, when we did haplotype analysis for these two polymorphisms, the 91A-169G haplotype was associated with protection from HNPCC at an earlier age.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Alleles
  • Aurora Kinases
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / enzymology
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / epidemiology
  • Colorectal Neoplasms, Hereditary Nonpolyposis* / genetics
  • European Continental Ancestry Group
  • Female
  • Germ-Line Mutation
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Protein-Serine-Threonine Kinases / genetics*

Substances

  • Aurora Kinases
  • Protein-Serine-Threonine Kinases