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Genetic variants associated with breast cancer risk for Ashkenazi Jewish women with strong family histories but no identifiable BRCA1/2 mutation

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Title Genetic variants associated with breast cancer risk for Ashkenazi Jewish women with strong family histories but no identifiable BRCA1/2 mutation
 
Creator Rinella, E S
Shao, Y
Yackowski, L
Pramanik, S
Oratz, R
Schnabel, F
Guha, S
LeDuc, C
Campbell, C L
Klugman, S D
Terry, M B
Senie, R T
Andrulis, I L
Daly, M
John, E M
Roses, D
Chung, W K
Ostrer, H
 
Subject Environmental Health
 
Description The ability to establish genetic risk models is
critical for early identification and optimal treatment of
breast cancer. For such a model to gain clinical utility,
more variants must be identified beyond those discovered
in previous genome-wide association studies (GWAS).
This is especially true for women at high risk because of
family history, but without BRCA1/2 mutations. This study
incorporates three datasets in a GWAS analysis of women
with Ashkenazi Jewish (AJ) homogeneous ancestry. Two
independent discovery cohorts comprised 239 and 238 AJ
women with invasive breast cancer or preinvasive ductal
carcinoma in situ and strong family histories of breast
cancer, but lacking the three BRCA1/2 founder mutations,
along with 294 and 230 AJ controls, respectively. An
independent, third cohort of 203 AJ cases with familial
breast cancer history and 263 healthy controls of AJ
women was used for validation. A total of 19 SNPs were
identified as associated with familial breast cancer risk in
AJ women. Among these SNPs, 13 were identified from a
panel of 109 discovery SNPs, including an FGFR2 haplotype.
In addition, six previously identified breast cancer
GWAS SNPs were confirmed in this population. Seven
of the 19 markers were significant in a multivariate predictive
model of familial breast cancer in AJ women, three
novel SNPs [rs17663555(5q13.2), rs566164(6q21), and
rs11075884(16q22.2)], the FGFR2 haplotype, and three previously published SNPs [rs13387042(2q35), rs2046210
(ESR1), and rs3112612(TOX3)], yielding moderate predictive
power with an area under the curve (AUC) of the
ROC (receiver-operator characteristic curve) of 0.74.
Population-specific genetic variants in addition to variants
shared with populations of European ancestry may improve
breast cancer risk prediction among AJ women from highrisk
families without founder BRCA1/2 mutations
 
Publisher Springer
 
Date 2013-05
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://neeri.csircentral.net/858/1/SreemantaHumanGenetics_2013.pdf
Rinella, E S and Shao, Y and Yackowski, L and Pramanik, S and Oratz, R and Schnabel, F and Guha, S and LeDuc, C and Campbell, C L and Klugman, S D and Terry, M B and Senie, R T and Andrulis, I L and Daly, M and John, E M and Roses, D and Chung, W K and Ostrer, H (2013) Genetic variants associated with breast cancer risk for Ashkenazi Jewish women with strong family histories but no identifiable BRCA1/2 mutation. Human Genetics, 132 (5). pp. 523-536. ISSN 0340-6717, ESSN: 1432-1203
 
Relation https://link.springer.com/journal/439
http://neeri.csircentral.net/858/