Prognostic impact of polymorphisms in the MYBL2 interacting genes in breast cancer.
MYBL2 is a transcription factor, which regulates the expression of genes involved in cancer progression. In this study, we investigated whether putative functional variants in genes regulating MYBL2 (E2F1, E2F3 and E2F4) or in genes, which are regulated by MYBL2 (BCL2, BIRC5, COL1A1, COL1A2, COL5A2, ERBB2, CLU, LIN9 and TOP2A) affect breast cancer (BC) susceptibility and clinical outcome. Twenty-eight SNPs were genotyped in a population-based series of 782 Swedish BC cases and 1,559 matched controls. BC-specific survival analysis of BIRC5 suggested that carriers of the minor allele of rs8073069 and rs1042489 have a worse survival compared with the major homozygotes (HR 2.46, 95% CI 1.39-4.36 and HR 1.81, 95% CI 1.01-3.25, respectively). The poor survival was observed especially in women with aggressive tumours. Multivariate analysis supported the role of rs8073069 as an independent prognostic marker. For BCL2, minor allele carriers of rs1564483 were more likely to have hormone receptor-positive tumours than the major homozygotes. Another SNP in BCL2, rs4987852, was associated with tumour stages II-IV and histologic grade 3. In CLU, the minor allele carriers of rs9331888 were more likely to have tumours with regional lymph node metastasis and stages II-IV than the major homozygotes. In conclusion, our study suggests a role of genetic variation in BIRC5, BCL2 and CLU as progression and prognostic markers for BC, supporting previous studies based on the expression of the genes.
Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120, Heidelberg, Germany.
Hong
H
Shi
Melanie
M
Bevier
Robert
R
Johansson
Kerstin
K
Enquist-Olsson
Roger
R
Henriksson
Kari
K
Hemminki
Per
P
Lenner
Asta
A
Försti
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D051152:Clusterin / Q000235:genetics; D005260:Female; D053263:Gene Regulatory Networks; D019254:Genes, bcl-2; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D015810:Linkage Disequilibrium; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016019:Survival Analysis; D000077022:Survivin; D013548:Sweden / Q000453:epidemiology; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D044465:White People / Q000235:genetics
C107489:BIRC5 protein, human; C495242:CLU protein, human; D018797:Cell Cycle Proteins; D051152:Clusterin; D051034:Inhibitor of Apoptosis Proteins; C064352:MYBL2 protein, human; D000077022:Survivin; D015534:Trans-Activators