TY - JOUR
T1 - ATM Polymorphism and hereditary nonpolyposis colorectal cancer (HNPCC) age of onset (United States)
AU - Jones, J. Shawn
AU - Gu, Xiangjun
AU - Lynch, Patrick M.
AU - Rodriguez-Bigas, Miguel
AU - Amos, Christopher I.
AU - Frazier, Marsha L.
N1 - Funding Information:
w This grant was supported by Grant CA70759 from the National Cancer Institute, by NIH Cancer Center Support Grant CA16672 and also, by a cancer prevention fellowship from the National Cancer Institute, Grant R25 CA57730. * Address correspondence to: Marsha L. Frazier, Ph.D., Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 189, Houston, TX 77030, USA. Ph.: 713-792-3393; Fax: 713-745-1163; E-mail: mlfrazier@mdanderson.org
PY - 2005/8
Y1 - 2005/8
N2 - 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. Materials and 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.
AB - 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. Materials and 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.
KW - ATM
KW - Age of onset
KW - Familial and hereditary cancers
KW - Genotype-phenotype interactions
KW - Hereditary nonpolyposis colorectal cancer
KW - Single nucleotide polymorphism
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U2 - 10.1007/s10552-005-1540-7
DO - 10.1007/s10552-005-1540-7
M3 - Article
C2 - 16049814
AN - SCOPUS:23444446244
SN - 0957-5243
VL - 16
SP - 749
EP - 753
JO - Cancer Causes and Control
JF - Cancer Causes and Control
IS - 6
ER -