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Low‐risk variants FGFR2 , TNRC9 and LSP1 in German familial breast cancer patients
Author(s) -
Hemminki Kari,
MüllerMyhsok Bertram,
Lichtner Peter,
Engel Christoph,
Chen Bowang,
Burwinkel Barbara,
Försti Asta,
Sutter Christian,
Wappenschmidt Barbara,
Hellebrand Heide,
Illig Thomas,
Arnold Norbert,
Niederacher Dieter,
Dworniczak Bernd,
Deissler Helmut,
Kast Karin,
Gadzicki Dorothea,
Meitinger Thomas,
Wichmann H.Erich,
Kiechle Marion,
Bartram Claus R.,
Schmutzler Rita K.,
Meindl Alfons
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24986
Subject(s) - german , breast cancer , medicine , cancer , oncology , gynecology , linguistics , philosophy
Abstract To validate common low‐risk variants predisposing for breast cancer (BC) in a large set of BRCA1/2 negative familial or genetically enriched cases from Germany, we genotyped 1,415 cases and 1,830 healthy women by MALDI‐TOF in 105 candidate SNPs. Significantly higher ORs than previously reported for heterozygous unselected cases were found for the minor allele in FGFR2 (OR = 1.43, 95% CI 1.30‐1.59, p‐value = 1.24 × 10 −12 ) and for TNRC9 (OR = 1.33, 95% CI 1.19‐1.46, p‐value = 1.54 × 10 −7 ). 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 × 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 BC 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 BC cases and correlate them to specific histopathological subtypes defined by estrogen receptor status.