 |
 |
|
Home |
Current Issue |
Past Issues |
In the Clinic |
ACP Journal Club |
CME |
Collections |
Audio/Video |
Mobile |
Subscribe |
Tools |
Help |
ACP Online
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
21 November 2000 | Volume 133 Issue 10 | Pages 770-778
Background: Mutations at the ataxia-telangiectasia locus cause a distinctive autosomal recessive syndrome in homozygotes and predispose heterozygotes to cancer and ischemic heart disease.
Objective: To examine mortality rates among persons carrying a mutated ataxia-telangiectasia gene.
Design: Retrospective cohort study.
Setting: The United States and Canada.
Participants: 405 grandparents of patients with ataxia-telangiectasia.
Measurements: Ages at death and risk for death (from all causes, cancer, ischemic heart disease, and other causes) among carriers and noncarriers of ataxia-telangiectasia mutations.
Results: Compared with noncarriers, carriers of a mutated ataxia-telangiectasia allele had a significantly increased risk for death at 20 through 79 years of age (relative risk, 1.9 [95% CI, 1.3 to 2.8]) (P < 0.001). On average, carriers died 7 to 8 years earlier than noncarriers. Cancer caused most of the excess deaths, and ischemic heart disease caused the remainder. Among carriers, relative risk for death from cancer and ischemic heart disease before 80 years of age was 2.6 (CI, 1.4 to 4.7; P = 0.002) and 2.0 (CI, 1.0 to 4.0; P = 0.062), respectively. Compared with noncarriers, carriers who died of cancer were a mean of 4 years younger (P > 0.2) and carriers who died of ischemic heart disease were a mean of 11 years younger (P = 0.006).
Conclusion: Carriers of mutations at the ataxia-telangiectasia locus, who make up 1.4% to 2% of the general population, have a higher mortality rate and an earlier age at death from cancer and ischemic heart disease than noncarriers.
Author and Article Information
From New York Medical College, Hawthorne, New York.
Acknowledgments: The authors thank Ruby Massey and Patricia Rentas for sample and data collection; Airong Li, MD, DPhil, and Prasanna Athma, PhD, for genotyping; Ronnie Gorman Swift, MD, for reviewing earlier versions of the manuscript; and the participating families, who have made the study possible.
Grant Support: By the National Institutes of Health (CA 14235).
Current Author Addresses: Drs. Su and Swift: The Institute for the Genetic Analysis of Common Diseases, New York Medical College, 4 Skyline Drive, Hawthorne, NY 10532.
Author Contributions: Conception and design: Y. Su, M. Swift.
Analysis and interpretation of the data: Y. Su, M. Swift.
Drafting of the article: Y. Su, M. Swift.
Critical revision of the article for important intellectual content: Y. Su, M. Swift.
Final approval of the article: Y. Su, M. Swift.
Provision of study materials or patients: M. Swift.
Statistical expertise: Y. Su.
Obtaining of funding: M. Swift.
Administrative, technical, or logistic support: M. Swift. ARTICLE
Mortality Rates among Carriers of Ataxia-Telangiectasia Mutant Alleles
Related articles in Annals:
This article has been cited by other articles:
|
|
 |
|
  M. B. Kastan DNA Damage Responses: Mechanisms and Roles in Human Disease: 2007 G.H.A. Clowes Memorial Award Lecture Mol. Cancer Res., April 1, 2008; 6(4): 517 - 524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Calderon-Margalit, Y. Friedlander, R. Yanetz, L. Deutsch, O. Manor, S. Harlap, and O. Paltiel Late Stillbirths and Long-Term Mortality of Mothers Obstet. Gynecol., June 1, 2007; 109(6): 1301 - 1308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Mahmoudi, J. Mercer, and M. Bennett DNA damage and repair in atherosclerosis Cardiovasc Res, July 15, 2006; 71(2): 259 - 268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Thompson, S. Duedal, J. Kirner, L. McGuffog, J. Last, A. Reiman, P. Byrd, M. Taylor, and D. F. Easton Cancer Risks and Mortality in Heterozygous ATM Mutation Carriers J Natl Cancer Inst, June 1, 2005; 97(11): 813 - 822. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Angele, P. Romestaing, N. Moullan, M. Vuillaume, B. Chapot, M. Friesen, W. Jongmans, D. G. Cox, P. Pisani, J.-P. Gerard, et al. ATMHaplotypes and Cellular Response to DNA Damage: Association with Breast Cancer Risk and Clinical Radiosensitivity Cancer Res., December 15, 2003; 63(24): 8717 - 8725. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. R. Willett Annual screening with mammography and breast examination did not reduce breast cancer mortality in women 40-49 years of age Evid. Based Med., March 1, 2003; 8(2): 44 - 44. [Full Text] [PDF]
|
|
|
|
|
|
L. R. Willett Review: mammography reduces breast cancer mortality rates Evid. Based Med., March 1, 2003; 8(2): 45 - 45. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Gronbak, J. Worm, E. Ralfkiaer, V. Ahrenkiel, P. Hokland, and P. Guldberg ATM mutations are associated with inactivation of the ARF-TP53 tumor suppressor pathway in diffuse large B-cell lymphoma Blood, July 30, 2002; 100(4): 1430 - 1437. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. Scott, R. Bendix, P. Chen, R. Clark, T. Dork, and M. F. Lavin Missense mutations but not allelic variants alter the function of ATM by dominant interference in patients with breast cancer PNAS, January 22, 2002; 99(2): 925 - 930. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Su and M. Swift Outcomes of Adjuvant Radiation Therapy for Breast Cancer in Women With Ataxia-Telangiectasia Mutations JAMA, November 14, 2001; 286(18): 2233 - 2234. [Full Text] [PDF]
|
|
|
|
|
|
T. Dork, R. Bendix, M. Bremer, D. Rades, K. Klopper, M. Nicke, B. Skawran, A. Hector, P. Yamini, D. Steinmann, et al. Spectrum of ATM Gene Mutations in a Hospital-based Series of Unselected Breast Cancer Patients Cancer Res., October 1, 2001; 61(20): 7608 - 7615. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Swift Public Health Burden of Cancer in Ataxia-Telangiectasia Heterozygotes J Natl Cancer Inst, January 17, 2001; 93(2): 84 - 85. [Full Text] [PDF]
|
|
Article
