Genes harbouring susceptibility SNPs are differentially expressed in the breast cancer subtypes.
Recently, genome-wide association studies of breast cancer revealed single nucleotide polymorphisms (SNPs) in five genes with novel association to susceptibility. While there is little doubt that the novel susceptibility markers produced from such highly powered studies are true, the mechanisms by which they cause the susceptibility remain undetermined. We have looked at the expression levels of the identified genes in tumours and found that they are highly significantly differentially expressed between the five established breast cancer subtypes. Also, a significant association between SNPs in these genes and their expression in tumours was seen as well as a significantly different frequency of the SNPs between the subtypes. This suggests that the observed genes are associated with different breast cancer subtypes, and may exert their effect through their expression in the tumours. Thus, future studies stratifying patients by their molecular subtypes may give much more power to classic case control studies, and genes of no or borderline significance may appear to be high-penetrant for certain subtypes and, therefore, be identifiable.
Department of Genetics, Institute of Cancer Research, Rikshospitalet-Radiumhospitalet Medical Centre, Montebello, N-0310 Oslo, Norway.
Silje H
SH
Nordgard
Fredrik E
FE
Johansen
Grethe I G
GI
Alnaes
Bjørn
B
Naume
Anne-Lise
AL
Børresen-Dale
Vessela N
VN
Kristensen
D000704:Analysis of Variance; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006609:High Mobility Group Proteins; D006801:Humans; D048728:MAP Kinase Kinase Kinase 1 / Q000032:analysis / Q000235:genetics; D008840:Microfilament Proteins / Q000032:analysis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000032:analysis / Q000235:genetics; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000032:analysis / Q000235:genetics; D011980:Receptors, Progesterone / Q000032:analysis / Q000235:genetics; D015534:Trans-Activators; D015854:Up-Regulation
D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; C094335:H19 long non-coding RNA; D006609:High Mobility Group Proteins; C489183:LSP1 protein, human; D008840:Microfilament Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D011980:Receptors, Progesterone; C521752:TOX3 protein, human; D015534:Trans-Activators; C496353:FGFR2 protein, human; D051497:Receptor, Fibroblast Growth Factor, Type 2; D048728:MAP Kinase Kinase Kinase 1; C482576:MAP3K1 protein, human