The relationship between twenty missense ATM variants and breast cancer risk: The multiethnic cohort Journal Article


Authors: Bretsky, P.; Haiman, C. A.; Gilad, S.; Yahalom, J.; Grossman, A.; Paglin, S.; Van den Berg, D.; Kolonel, L. N.; Skaliter, R.; Henderson, B. E.
Article Title: The relationship between twenty missense ATM variants and breast cancer risk: The multiethnic cohort
Abstract: 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 over-represented 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.
Keywords: adult; controlled study; aged; middle aged; major clinical study; case control study; missense mutation; dna-binding proteins; mutation, missense; cancer risk; cell cycle proteins; dna damage; dna repair; disease association; cohort studies; breast cancer; cohort analysis; genetic variability; breast neoplasms; heterozygote; prediction; confidence interval; chromosome aberration; statistical significance; protein-serine-threonine kinases; population; tumor suppressor proteins; familial cancer; asia; african americans; european continental ancestry group; japan; polymorphism, genetic; caucasian; negro; dna polymorphism; ethnic groups; ataxia telangiectasia; hispanic americans; ethnology; asian americans; variation (genetics); humans; human; female; priority journal; article
Journal Title: Cancer Epidemiology Biomarkers and Prevention
Volume: 12
Issue: 8
ISSN: 1055-9965
Publisher: American Association for Cancer Research  
Date Published: 2003-08-01
Start Page: 733
End Page: 738
Language: English
PUBMED: 12917204
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 12 September 2014 -- Source: Scopus