Association between Aurora-A kinase polymorphisms and age of onset of hereditary nonpolyposis colorectal cancer in a Caucasian population.
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.
Chen
Jinyun
J
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Sen
Subrata
S
Amos
Christopher I
CI
Wei
Chongjuan
C
Jones
J Shawn
JS
Lynch
Patrick
P
Frazier
Marsha L
ML
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D064127:Aurora Kinases; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D044465:White People
D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases