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| Heterozygous ATM mutations do not contribute to early onset of breast cancer |
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| Author(s): FitzGerald MG, Bean JM, Hegde SR, Unsal H, MacDonald DJ, Harkin DP, Finkelstein DM, Isselbacher KJ, Haber DA |
| Source: NATURE GENETICS Volume: 15 Issue: 3 Pages: 307-310 Published: MAR 1997 |
| Times Cited: 222 References: 39 |
| Abstract: Ataxia telangiectasia (AT) is a recessive syndrome, including cerebellar degeneration, immunologic defects and cancer predisposition(1,2), attributed to mutations in the recently isolated ATM (ataxia telangiectasia, mutated) gene(3). AT is diagnosed in 1/40,000 to 1/100,000 live births, with carriers calculated to comprise similar to 1% of the population. Studies of AT families have suggested that female relatives presumed to be carriers have a 5 to 8-fold increased risk for developing breast cancer(4,5), raising the possibility that germline ATM mutations may account for similar to 5% of all breast cancer cases. The increased risk for breast cancer reported for AT family members has been most evident among younger women, leading to an age-specific relative risk model predicting that 8% of breast cancer in women under age 40 arises in AT carriers, compared with 2% of cases between 40-59 years(6). To test this hypothesis, we undertook a germ-line mutational analysis of the ATM gene in a population of women with early onset of breast cancer, using a protein truncation (PTT) assay to detect chain-terminating mutations, which account for 90% of mutations identified in children with AT(7-11). We detected a heterozygous ATM mutation in 2/202 (1%) controls, consistent with the frequency of AT carriers predicted from epidemiologic studies. ATM mutations were present in only 2/401 (0.5%) women with early onset of breast cancer (P = 0.6). We conclude that heterozygous ATM mutations do not confer genetic predisposition to early onset of breast cancer. |
| Document Type: Article |
| Language: English |
Addresses:
1. MASSACHUSETTS GEN HOSP, CTR CANC, CTR CANC RISK ANAL, CHARLESTOWN, MA 02129 USA
2. MASSACHUSETTS GEN HOSP, CTR CANC, DEPT BIOSTAT, CHARLESTOWN, MA 02129 USA
3. HARVARD UNIV, SCH MED, CHARLESTOWN, MA 02129 USA |
| Publisher: NATURE PUBLISHING CO, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 |
| Subject Category: Genetics & Heredity |
| IDS Number: WK386 |
| ISSN: 1061-4036 |
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