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Hemminki, K.* ; Müller-Myhsok, B.* ; Lichtner, P. ; Engel, C.* ; Chen, B.* ; Burwinkel, B.* ; Försti, A.* ; Sutter, C.* ; Wappenschmidt, B.* ; Hellebrand, H.* ; Illig, T. ; Arnold, N.* ; Niederacher, D.* ; Dworniczak, B.* ; Deissler, H.* ; Kast, K.* ; Gadzicki, D.* ; Meitinger, T. ; Wichmann, H.-E. ; Kiechle, M.* ; Bartram, C.R.* ; Schmutzler, R.K.* ; Meindl, A.*

Low risk variants FGFR2, TNRC9 and LSP1 in German familial breast cancer patients.

Int. J. Cancer 126, 2858-2862 (2010)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
To validate common low risk variants predisposing for breast cancer in a large set of BRCA1/2 negative familial or genetically enriched cases from Germany, we genotyped 1415 cases and 1830 healthy women by MALDI-TOF in 105 candidate SNPs. A significantly higher OR than previously reported for heterozygous unselected cases was found for the minor allele in FGFR2 (OR = 1.43, 95%CI 1.30-1.59, p-value = 1.24 x 10(-12)), while an OR approaching genome-wide significance was found for TNRC9 (OR = 1.33, 95%CI 1.19-1.46, p-value = 1.54 x 10(-7)) in familial cases. Most intriguing however, were the ORs for homozygous carriers from high risk families for FGFR2 (OR = 2.05, 95%CI 1.68-2.51, LSP1 (OR = 0.49, 95%CI 0.28-0.86) and TNRC9 (OR = 1.62, 95%CI 1.27-2.07). Moreover, the additional validation of 99 CGEMS-SNPs identified putative novel susceptibility alleles within the LSP1 gene (OR = 0.73, 95%CI 0.61-0.87, p-value = 5.23 x 10(-4)). Finally, we provide evidence for the first time that a low risk variant located at 6q22.33 (rs6569479) is associated with estrogen receptor negative breast cancer in familial cases (OR = 1.33, 95%CI 1.06-1.66; p-value = 0.012). Our data confirm the impact of the previously identified susceptibility loci and provide preliminary evidence for novel susceptibility loci in familial breast cancer cases and correlate them to specific histopathological subtypes defined by estrogen receptor status.
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Publication type Article: Journal article
Document type Scientific Article
Keywords SNP; CGEMS; Familial breast cancer; Polymorphism; Breast cancer risk
Language
Publication Year 2010
Prepublished in Year 2009
HGF-reported in Year 2009
ISSN (print) / ISBN 0020-7136
e-ISSN 1097-0215
Journal International Journal of Cancer
Quellenangaben Volume: 126, Issue: 126, Pages: 2858-2862 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken, NJ
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
Institute of Epidemiology (EPI)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30503 - Chronic Diseases of the Lung and Allergies
Research field(s) Genetics and Epidemiology
PSP Element(s) G-500700-001
G-503900-001
G-503900-003
PubMed ID 19856316
DOI 10.1002/ijc.24986
Scopus ID 77951911594
Erfassungsdatum 2009-12-31
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