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

Hemminki, Kari LU ; Mueller-Myhsok, Bertram; Lichtner, Peter; Engel, Christoph; Chen, Bowang; Burwinkel, Barbara; Försti, Asta LU ; Sutter, Christian; Wappenschmidt, Barbara and Hellebrand, Heide, et al. (2010) In International Journal of Cancer 126(12). p.2858-2862
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% Cl 1.30-1.59, p-value = 1.24 x 10(-12)) and for TNRC9 (OR = 1.33, 95% Cl 1.19-1.46, p-value = 1.54 x 10(-7)). Most intriguing, however, were the ORs for homozygous carriers from high-risk families for FGFR2 (OR = 2.05, 95% Cl 1.68-2.51, LSP1 (OR = 0.49, 95% Cl 0.28-0.86) and TNRC9 (OR = 1.62, 95% Cl 1.27-2.07). Moreover, the additional validation of 99... (More)
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% Cl 1.30-1.59, p-value = 1.24 x 10(-12)) and for TNRC9 (OR = 1.33, 95% Cl 1.19-1.46, p-value = 1.54 x 10(-7)). Most intriguing, however, were the ORs for homozygous carriers from high-risk families for FGFR2 (OR = 2.05, 95% Cl 1.68-2.51, LSP1 (OR = 0.49, 95% Cl 0.28-0.86) and TNRC9 (OR = 1.62, 95% Cl 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% Cl 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 BC in familial cases (OR = 1.33, 95% Cl 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. (Less)
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publication status
published
subject
keywords
breast cancer risk, polymorphism, familial breast cancer, SNP, CGEMS
in
International Journal of Cancer
volume
126
issue
12
pages
2858 - 2862
publisher
John Wiley & Sons
external identifiers
  • wos:000277551100010
  • scopus:77951911594
ISSN
0020-7136
DOI
10.1002/ijc.24986
language
English
LU publication?
yes
id
0d1ee085-50ec-442d-8f96-a15c4026dc47 (old id 1617852)
date added to LUP
2010-06-21 16:12:30
date last changed
2018-05-29 12:18:01
@article{0d1ee085-50ec-442d-8f96-a15c4026dc47,
  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% Cl 1.30-1.59, p-value = 1.24 x 10(-12)) and for TNRC9 (OR = 1.33, 95% Cl 1.19-1.46, p-value = 1.54 x 10(-7)). Most intriguing, however, were the ORs for homozygous carriers from high-risk families for FGFR2 (OR = 2.05, 95% Cl 1.68-2.51, LSP1 (OR = 0.49, 95% Cl 0.28-0.86) and TNRC9 (OR = 1.62, 95% Cl 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% Cl 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 BC in familial cases (OR = 1.33, 95% Cl 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.},
  author       = {Hemminki, Kari and Mueller-Myhsok, Bertram and Lichtner, Peter and Engel, Christoph and Chen, Bowang and Burwinkel, Barbara and Försti, Asta and Sutter, Christian and Wappenschmidt, Barbara and Hellebrand, Heide and Illig, Thomas and Arnold, Norbert and Niederacher, Dieter and Dworniczak, Bernd and Deissler, Helmut and Kast, Karin and Gadzicki, Dorothea and Meitinger, Thomas and Wichmann, H. -Erich and Kiechle, Marion and Bartram, Claus R. and Schmutzler, Rita K. and Meindl, Alfons},
  issn         = {0020-7136},
  keyword      = {breast cancer risk,polymorphism,familial breast cancer,SNP,CGEMS},
  language     = {eng},
  number       = {12},
  pages        = {2858--2862},
  publisher    = {John Wiley & Sons},
  series       = {International Journal of Cancer},
  title        = {Low-risk variants FGFR2, TNRC9 and LSP1 in German familial breast cancer patients},
  url          = {http://dx.doi.org/10.1002/ijc.24986},
  volume       = {126},
  year         = {2010},
}