NDLI: A multi-stage association study identifies a breast cancer genetic locus at NCOA7

Content Provider	PubMed Central
Author	Higginbotham, Kathryn S. P. Breyer, Joan P. Bradley, Kevin M. Schuyler, Peggy A. Plummer, W. Dale Freudenthal, Marcia E. Amy, Trentham-dietz Newcomb, Polly A. Sanders, Melinda E. Page, David L. Parl, Fritz F. Egan, Kathleen M. Dupont, William D. Smith, Jeffrey R.
Abstract	Estrogen metabolism and growth factor signaling pathway genes play key roles in breast cancer development. We evaluated associations between breast cancer and tagging SNPs of 107 candidate genes of these pathways using single allele- and haplotype-based tests. We first sought concordance of associations between two study populations: the Nashville Breast Cohort (510 cases, 988 controls), and the Cancer Genetic Markers of Susceptibility breast cancer study (1,145 cases, 1,142 controls). Findings across the two study populations were concordant at tagging SNPs of six genes, and at previously published SNPs of FGFR2. We sought further replication of results for EGFR, NCOA7, and FGFR2 in the independent Collaborative Breast Cancer Study (1,552 cases, 1,185 controls). Associations at NCOA7 and FGFR2 replicated across all three studies. The association at NCOA7 on 6q22.32, detected by a haplotype spanning the initial protein-coding exon (5′ - rs9375411, rs11967627, rs549438, rs529858, rs490361, rs17708107 - 3′), has not been previously reported. The haplotype had a significant inverse association with breast cancer in each study (ORHet 0.69 (NBC), 0.76 (CGEMS), 0.79 (CBCS)), and a meta-analysis ORHet of 0.75 (95% CI 0.65-0.87, P = 1.4 × 10-4) in the combined study populations. The haplotype frequency was 0.07 among cases, and 0.09 among controls; homozygotes were infrequent and each ORHom was not significant. NCOA7 encodes a nuclear receptor co-activator that interacts with estrogen receptor α to modulate its activity. These observations provide consistent evidence that genetic variants at the NCOA7 locus may confer a reduced risk of breast cancer.
Related Links	http://dx.doi.org/10.1158/0008-5472.can-10-2653
Ending Page	3888
Page Count	8
Starting Page	3881
File Format	PDF
ISSN	00085472
e-ISSN	15387445
Journal	Cancer research
Issue Number	11
Volume Number	71
Language	English
Publisher Date	2011-06-01
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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