This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bretsky, P. Articles by Henderson, B. E. Search for Related Content PubMed PubMed Citation Articles by Bretsky, P. Articles by Henderson, B. E.

The Relationship between Twenty Missense ATM Variants and Breast Cancer Risk

The Multiethnic Cohort¹

University of Southern California/Norris Comprehensive Cancer Center, Department of Preventive Medicine, Keck School of Medicine of the University of Southern California, Los Angeles, California 90033 [P. B., C. A. H., D. V. D. B., B. E. H.]; Quark Biotech Ltd., Nes Ziona, 70400, Israel [S. G., A. G., R. S.]; Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021 [J. Y., S. P.]; and Etiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu, Hawaii 96813 [L. N. K.]

Deficiencies in tasks of detecting and repairing DNA damage lead to mutations and chromosomal abnormalities, a hallmark of cancer. The gene mutated in ataxia-telangiectasia (A-T), ATM, is a proximal component in performing such tasks. Studies of A-T families have suggested an increased risk of breast cancer among obligate female heterozygous carriers of ATM mutations. Paradoxically, studies of sporadic and familial breast cancer have failed to demonstrate an elevated prevalence of mutations among breast cancer cases. We characterized the prevalence and distribution of 20 ATM missense mutations/polymorphisms in a population-based case-control study of 854 African-American, Latina, Japanese, and Caucasian women aged 45 years participating in the Multiethnic Cohort Study. The study population included 428 incident breast cancer cases and 426 controls. The prevalence of variants ranged from 0% to 13.6% among controls and varied by ethnicity (0–32.5%). Overall, these data provide little support for an association of ATM missense mutations with breast cancer among older women. We observed only one sequence variation (L546V), common among African-American women, to be overrepresented among all high-stage breast cancer cases (odds ratio, 3.35; 95% confidence interval, 1.27–8.84). After correction for multiple comparisons, this observed risk modification did not attain statistical significance. The distribution of ATM missense mutations and polymorphisms varied widely across the four ethnic groups studied. Although a single missense variant (L546V) appeared to act as a modest predictor of risk, the remaining variants were no more common in breast cancer cases as compared with controls.

This article has been cited by other articles:

				J. H. Kim, H. Kim, K. Y. Lee, K.-H. Choe, J.-S. Ryu, H. I. Yoon, S. W. Sung, K.-Y. Yoo, and Y.-C. Hong Genetic polymorphisms of ataxia telangiectasia mutated affect lung cancer risk Hum. Mol. Genet., April 1, 2006; 15(7): 1181 - 1186. [Abstract] [Full Text] [PDF]

				K.-M. Lee, J.-Y. Choi, S. K. Park, H.-W. Chung, B. Ahn, K.-Y. Yoo, W. Han, D.-Y. Noh, S.-H. Ahn, H. Kim, et al. Genetic Polymorphisms of Ataxia Telangiectasia Mutated and Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., April 1, 2005; 14(4): 821 - 825. [Abstract] [Full Text] [PDF]

				C. I. Szabo, M. Schutte, A. Broeks, J. J. Houwing-Duistermaat, Y. R. Thorstenson, F. Durocher, R. A. Oldenburg, M. Wasielewski, F. Odefrey, D. Thompson, et al. Are ATM Mutations 7271T->G and IVS10-6T->G Really High-Risk Breast Cancer-Susceptibility Alleles? Cancer Res., February 1, 2004; 64(3): 840 - 843. [Abstract] [Full Text] [PDF]