ATM polymorphism and hereditary nonpolyposis colorectal cancer (HNPCC) age of onset (United States).
OBJECTIVE
We examined a G-to-A single nucleotide polymorphism of the ATM gene, to determine if it influences hereditary non-polyposis colorectal cancer (HNPCC) age of onset. HNPCC is caused by mutations in mismatch repair genes, especially hMLH1 and hMSH2. ATM germline mutations have been associated with breast and digestive cancers. In a smaller European study, the G-to-A polymorphism was associated with an increased risk of developing an HNPCC-related cancer within HNPCC families.


METHODS
We genotyped 109 mismatch repair gene (MMR) mutation carriers from 53 HNPCC families for the ATM polymorphism using PCR and single strand conformational polymorphism (SSCP) analysis. We tested the association between the ATM genotypes and HNPCC age of onset by survival analysis.


RESULTS
The ATM polymorphism did not significantly modify HNPCC age of onset, nor overall risk, in our population.


CONCLUSIONS
Although a modifier effect was not seen in our study, future studies that examine the polymorphism in combination with other genetic and environmental factors may elucidate an association. Revealing such associations in MMR mutation carriers may improve risk estimates and help to identify individuals who are genetically susceptible to developing HNPCC at an earlier age.
Jones
J Shawn
JS
Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Gu
Xiangjun
X
Lynch
Patrick M
PM
Rodriguez-Bigas
Miguel
M
Amos
Christopher I
CI
Frazier
Marsha L
ML
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D064007:Ataxia Telangiectasia Mutated Proteins; D002352:Carrier Proteins / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000453:epidemiology / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D015996:Survival Rate; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D014481:United States / Q000453:epidemiology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein