Low-risk susceptibility alleles in 40 human breast cancer cell lines.
BACKGROUND
Low-risk breast cancer susceptibility alleles or SNPs confer only modest breast cancer risks ranging from just over 1.0 to 1.3 fold. Yet, they are common among most populations and therefore are involved in the development of essentially all breast cancers. The mechanism by which the low-risk SNPs confer breast cancer risks is currently unclear. The breast cancer association consortium BCAC has hypothesized that the low-risk SNPs modulate expression levels of nearby located genes.


METHODS
Genotypes of five low-risk SNPs were determined for 40 human breast cancer cell lines, by direct sequencing of PCR-amplified genomic templates. We have analyzed expression of the four genes that are located nearby the low-risk SNPs, by using real-time RT-PCR and Human Exon microarrays.


RESULTS
The SNP genotypes and additional phenotypic data on the breast cancer cell lines are presented. We did not detect any effect of the SNP genotypes on expression levels of the nearby-located genes MAP3K1, FGFR2, TNRC9 and LSP1.


CONCLUSIONS
The SNP genotypes provide a base line for functional studies in a well-characterized cohort of 40 human breast cancer cell lines. Our expression analyses suggest that a putative disease mechanism through gene expression modulation is not operative in breast cancer cell lines.
Riaz
Muhammad
M
Department of Medical Oncology, Josephine Nefkens Institute, Erasmus University Medical Center, Rotterdam, the Netherlands. m.riaz@erasmusmc.nl
Elstrodt
Fons
F
Hollestelle
Antoinette
A
Dehghan
Abbas
A
Klijn
Jan Gm
JG
Schutte
Mieke
M
D000483:Alleles; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D045744:Cell Line, Tumor; D005091:Exons; D020869:Gene Expression Profiling; D052138:Genes, Neoplasm; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012306:Risk