Linked Life Data

20306497

Source:http://linkedlifedata.com/resource/pubmed/id/20306497

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2010-5-31
pubmed:abstractText
Germline mutations in the BRCA1 and BRCA2 genes are associated with a significantly increased lifetime risk for developing breast and/or ovarian cancer. However, incomplete penetrance and substantial variability in age of disease onset among carriers of the same mutation suggests the involvement of additional modifier genes and/or environmental factors. Somatic inactivating mutations in the p53 gene and genes of the p53 pathway often accompany BRCA1/2-associated tumors. Therefore, we assessed whether these genes are modifiers of penetrance. We genotyped Jewish-Ashkenazi women for functional single-nucleotide polymorphisms (SNPs) in the AKT1 (C>T rs3730358) and the PERP (C>T rs2484067) genes that affect p53-mediated apoptosis, as well as two tag-SNPs in the CHEK2 (C>T rs743184) and the ZBRK1/ZNF350 (G>A rs2278414) genes that encode for proteins involved in growth arrest following DNA damage. The study population included 138 healthy women, 148 breast/ovarian cancer BRCA1/2 mutation carriers, 121 asymptomatic BRCA1/2 mutation carriers, and 210 sporadic noncarrier breast cancer patients. Utilizing lambda(2) and Kaplan-Meier analysis revealed a hazard ratio (HR) of 3.23 (95% CI: 1.44-54, P = 0.0184) for the TT genotype of AKT (rs3730358), HR = 2.105 (95% CI: 1.049-7.434, P = 0.039) for CHEK2 CC genotype (rs743184), and HR = 2.4743 (95% CI: 1.205-11.53, P = 0.022) for the AG genotype of ZBRK1/ZNF350 (rs2278414). No significant association between PERP variants and cancer was identified HR = 0.662 (95% CI: 0.289-1.324, P = 0.261). Our results suggest that genes that act upstream of p53, or participate in the DNA damage response, may modify the risk of cancer in women with mutant BRCA1/2 alleles.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1098-2744
pubmed:author
pubmed:copyrightInfo
(c) 2010 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
545-55
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Single-nucleotide polymorphisms in the p53 pathway genes modify cancer risk in BRCA1 and BRCA2 carriers of Jewish-Ashkenazi descent.
pubmed:affiliation
Laboratory of Genomic Applications, Department of Surgical Oncology, Sheba Medical Center, Tel-Hashomer, Israel.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't