Abstract:
:Candidate single-nucleotide polymorphisms (SNPs) were analyzed for associations to an unselected whole genome pool of tumor mRNA transcripts in 50 unrelated patients with breast cancer. SNPs were selected from 203 candidate genes of the reactive oxygen species pathway. We describe a general statistical framework for the simultaneous analysis of gene expression data and SNP genotype data measured for the same cohort, which revealed significant associations between subsets of SNPs and transcripts, shedding light on the underlying biology. We identified SNPs in EGF, IL1A, MAPK8, XPC, SOD2, and ALOX12 that are associated with the expression patterns of a significant number of transcripts, indicating the presence of regulatory SNPs in these genes. SNPs were found to act in trans in a total of 115 genes. SNPs in 43 of these 115 genes were found to act both in cis and in trans. Finally, subsets of SNPs that share significantly many common associations with a set of transcripts (biclusters) were identified. The subsets of transcripts that are significantly associated with the same set of SNPs or to a single SNP were shown to be functionally coherent in Gene Ontology and pathway analyses and coexpressed in other independent data sets, suggesting that many of the observed associations are within the same functional pathways. To our knowledge, this article is the first study to correlate SNP genotype data in the germ line with somatic gene expression data in breast tumors. It provides the statistical framework for further genotype expression correlation studies in cancer data sets.
journal_name
Proc Natl Acad Sci U S Aauthors
Kristensen VN,Edvardsen H,Tsalenko A,Nordgard SH,Sørlie T,Sharan R,Vailaya A,Ben-Dor A,Lønning PE,Lien S,Omholt S,Syvänen AC,Yakhini Z,Børresen-Dale ALdoi
10.1073/pnas.0601893103subject
Has Abstractpub_date
2006-05-16 00:00:00pages
7735-40issue
20eissn
0027-8424issn
1091-6490pii
0601893103journal_volume
103pub_type
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