Format

Send to

Choose Destination
Breast Cancer Res. 2004;6(4):R401-7. Epub 2004 Jun 2.

Frequency of the ATM IVS10-6T-->G variant in Australian multiple-case breast cancer families.

Author information

1
Familial Cancer Centre, Royal Melbourne Hospital, Melbourne, Australia. lindeman@wehi.edu.au

Abstract

BACKGROUND:

Germline mutations in the genes BRCA1 and BRCA2 account for only a proportion of hereditary breast cancer, suggesting that additional genes contribute to hereditary breast cancer. Recently a heterozygous variant in the ataxia-telangiectasia mutated (ATM) gene, IVS10-6T-->G, was reported by an Australian multiple-case breast cancer family cohort study (the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer) to confer a substantial breast cancer risk. Although this variant can result in a truncated ATM product, its clinical significance as a high-penetrance breast cancer allele or its role as a low-penetrance risk-modifier is controversial.

METHODS:

We determined the frequency of ATM IVS10-6T-->G variants in a cohort of individuals affected by breast and/or ovarian cancer who underwent BRCA1 and BRCA2 genetic testing at four major Australian familial cancer clinics.

RESULTS:

Seven of 495 patients (1.4%) were heterozygous for the IVS10-6T-->G variant; the carrier rate in unselected Australian women with no family history of breast cancer is reported to be 6 of 725 (0.83%) (P = 0.4). Two of the seven probands also harboured a pathogenic BRCA1 mutation and one patient had a BRCA1 unclassified variant of uncertain significance.

CONCLUSION:

These findings indicate that the ATM IVS10-6T-->G variant does not seem to occur at a significantly higher frequency in affected individuals from high-risk families than in the general population. A role for this variant as a low-penetrance allele or as a modifying gene in association with other genes (such as BRCA1) remains possible. Routine testing for ATM IVS10-6T-->G is not warranted in mutation screening of affected individuals from high-risk families.

PMID:
15217508
PMCID:
PMC468657
DOI:
10.1186/bcr806
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center