Rare alleles of the HRAS polymorphism do not modify the risk of breast or ovarian cancer in BRCA1 carriers
- McGill Univ., Montreal (Canada); and others
The presence of one of the rare alleles of a minisatellite polymorphism at the HRAS locus on chromosome 11p15 has been associated with a roughly two-fold increase in the risk of breast cancer. The BRCA1 gene on chromosome 17q12-21 is responsible for the majority of the families with the breast-ovarian cancer syndrome. It is estimated that 87% of BRCA1 carriers will be affected with breast cancer by age 70. The relative risk for premenopausal breast cancer in carriers, compared to non-carriers, is roughly 100. Because of the wide range in ages of onset of cancer among BRCA1 carriers, it is likely that additional factors modify the risk of cancer. The role of other modifying genetic loci has not been studied. Through haplotype analysis we have identified 199 female BRCA1 carriers above the age of 20 years in 25 linked families. 127 of these women have been diagnosed with cancer and 72 are currently healthy. DNA was available on 59 carriers. Each sample was typed for the HRAS polymorphism by PCR, using primers flanking the minisatellite. Rare alleles were identified in 18 carriers. The penetrance of the BRCA1 gene was not higher among those women who carried a rare HRAS allele (mean age of onset 49 years) than among those who carried two common alleles (mean age of onset 43 years) (p= 0.59; log rank test). Similar results were obtained for ovarian cancer. These data do not support the hypothesis that the HRAS locus modified the risk of cancer among carriers of mutations in BRCA1.
- OSTI ID:
- 133558
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0286
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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