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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1996-3-25
pubmed:abstractText
Women who carry a mutation in the BRCA1 gene (on chromosome 17q21), have an 80% risk of breast cancer and a 40% risk of ovarian cancer by the age of 70 (ref. 1). The variable penetrance of BRCA1 suggests that other genetic and non-genetic factors play a role in tumourigenesis in these individuals. The HRAS1 variable number of tandem repeats (VNTR) polymorphism, located 1 kilobase (kb) downstream of the HRAS1 proto-oncogene (chromosome 11p15.5) is one possible genetic modifier of cancer penetrance. Individuals who have rare alleles of the VNTR have an increased risk of certain types of cancers, including breast cancer (2-4). To investigate whether the presence of rare HRAS1 alleles increases susceptibility to hereditary breast and ovarian cancer, we have typed a panel of 307 female BRCA1 carriers at this locus using a PCR-based technique. The risk for ovarian cancer was 2.11 times greater for BRCA1 carriers harbouring one or two rare HRAS1 alleles, compared to carriers with only common alleles (P = 0.015). The magnitude of the relative risk associated with a rare HRAS1 allele was not altered by adjusting for the other known risk factors for hereditary ovarian cancer (5). Susceptibility to breast cancer did not appear to be affected by the presence of rare HRAS1 alleles. This study is the first to show the effect of a modifying gene on the penetrance of an inherited cancer syndrome.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1061-4036
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
309-11
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:8589723-Adult, pubmed-meshheading:8589723-Alleles, pubmed-meshheading:8589723-BRCA1 Protein, pubmed-meshheading:8589723-Base Sequence, pubmed-meshheading:8589723-Breast Neoplasms, pubmed-meshheading:8589723-Chromosomes, Human, Pair 11, pubmed-meshheading:8589723-Chromosomes, Human, Pair 17, pubmed-meshheading:8589723-DNA Primers, pubmed-meshheading:8589723-Female, pubmed-meshheading:8589723-Genes, ras, pubmed-meshheading:8589723-Genetic Predisposition to Disease, pubmed-meshheading:8589723-Humans, pubmed-meshheading:8589723-Minisatellite Repeats, pubmed-meshheading:8589723-Molecular Sequence Data, pubmed-meshheading:8589723-Neoplasm Proteins, pubmed-meshheading:8589723-Ovarian Neoplasms, pubmed-meshheading:8589723-Risk Factors, pubmed-meshheading:8589723-Transcription Factors
pubmed:year
1996
pubmed:articleTitle
Ovarian cancer risk in BRCA1 carriers is modified by the HRAS1 variable number of tandem repeat (VNTR) locus.
pubmed:affiliation
Division of Medical Genetics, Montreal General Hospital, Quebec, Canada.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't