Molecular characterization of a cancer-related single nucleotide polymorphism in the pro-inflammatory interleukin-1B gene
Article first published online: 29 MAR 2012
Copyright © 2012 Wiley Periodicals, Inc.
Special Issue: Gene Polymorphisms and Susceptibility to Cancer
Volume 51, Issue S1, pages E168–E175, October 2012
How to Cite
Landvik, N.E., Tekpli, X., Anmarkrud, K.H., Haugen, A. and Zienolddiny, S. (2012), Molecular characterization of a cancer-related single nucleotide polymorphism in the pro-inflammatory interleukin-1B gene. Mol. Carcinog., 51: E168–E175. doi: 10.1002/mc.21910
- Issue published online: 4 OCT 2012
- Article first published online: 29 MAR 2012
- Manuscript Accepted: 7 MAR 2012
- Manuscript Revised: 16 FEB 2012
- Manuscript Received: 27 OCT 2011
- Norwegian Research Council
- Norwegian Cancer Society
- lung cancer;
Interleukin-1β is a key pro-inflammatory cytokine that has been associated with chronic inflammation and inflammation-related cancer initiation and progression. There are inter-individual differences in IL1B expression which may be due to single nucleotide polymorphisms (SNPs) in the regulatory regions of the gene. We have previously shown that a SNP located in the promoter of the IL1B gene (the IL1B T-31C SNP) was associated with lung cancer risk. Interestingly, the presence of the C allele was also associated with reduced IL1B expression in normal lung tissue of lung cancer patients. In the present study, we found that differential binding patterns of nuclear proteins to oligonucleotide probes containing the IL1B -31C allele compared to those with the T allele were due to specific binding of the transcription factor Yin Yang 1 (YY1). We further found evidence that specific recruitment of YY1 to the -31C region of the IL1B promoter regulated IL1B gene expression using siRNA directed towards YY1. The results indicate that the presence of a C allele at the -31 position may lead to decreased expression of the IL1B gene due to a specific binding of YY1 in lung epithelial cells. Our study provides functional significance of allelic variation at a single locus in the IL1B promoter and contributes to understanding the regulation of IL1B in inflammation-related carcinogenesis. © 2012 Wiley Periodicals, Inc.