Haugen, Aage

Landvik, Nina E

Skaug, Vidar

Zienolddiny, Shanbeh

BMC Proceedings

English

PubMed

Nina E Landvik

Shanbeh Zienolddiny

Vidar Skaug

Aage Haugen

Springer - Publisher Connector

ORAL PRESENTATION Open Access
Gene variants and lung cancer risk
Nina E Landvik, Shanbeh Zienolddiny, Vidar Skaug, Aage Haugen*
From 16th International Charles Heidelberger Symposium on Cancer Research
Coimbra, Portugal. 26–28 September 2010
Active smoking accounts for 90% of lung cancer deaths,
but only 15% of smokers develop lung cancer. Screening
for single-nucleotide polymorphisms (SNPs) in candi-
date pathway genes is an approach to defining high-risk
subgroup. Polymorphisms have been investigated to
determine whether variations in phase I and phase II
metabolism, DNA repair genes and inflammatory genes
predict risk of lung cancer, and susceptibility loci have
been identified in GWA studies. Pulmonary inflamma-
tion together with chemical exposure may potentiate the
carcinogenic process, underlying the importance of
inflammation in cancer development. Interleucin-1beta
(IL-1b) encoded by the IL1B gene, has been associated
with chronic inflammation and plays an important role
in lung inflammatory diseases, including COPD and
lung cancer. There are large interindividual differences
in IL1B gene expression, which may be explained
genetically by presence of SNPs scattered throughout
the regulatory region (rSNPs) of the gene. Our studies
have shown that several polymorphisms located in the
promoter and the enhancer regions of the IL1B gene
may affect risk of non-small cell lung cancer. These
rSNPs may affect IL1B expression by changing the bind-
ing affinity of transcription factors or creating novel
transcription binding sites. Notably, rSNPs at -3893 G,
-1464 G, -511 C and -31 T position formed a specific
haplotype (GGCT) with near complete linkage disequili-
brium in lung cancer patients, but not in controls where
the risk haplotype (GGCT) was present in 65% of cases
compared with 36% of controls. The risk haplotype was
correlated with significantly higher IL1B mRNA levels in
the lung of lung cancer patients. Particularly, we found
that the T to C SNP at the -31 position which is located
close to the transcription start site of the gene resulted
in binding of different transcription factors to the C and
T variants. We have further characterized the specific
transcription factors binding to the -31 SNP. In DNA-
protein interaction studies using Electrophoretic Mobi-
lity Shift Assay (EMSA) and human lung epithelial cells
we found evidence that the transcription factor Ying
Yang 1 (YY1) bound preferentially to the C SNP. The
binding of YY1 to the C SNP was further confirmed
using Chromatin Immunoprecipitation (ChIP) assay in
human lung epithelial cells. In summary, we have char-
acterized transcription factors that may interact differen-
tially with base changes in the SNPs and thereby may
explain the biological effects of the SNPs in modifying
the risk to lung cancer.
Published: 24 September 2010
doi:
Cite this article as: Landvik et al.: Gene variants and lung cancer risk.
BMC Proceedings 2010 4(Suppl 2):O3.
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* Correspondence: age.haugen@stami.no
Section of Toxicology, National Institute of Occupational Health, Oslo,
Norway
Full list of author information is available at the end of the article
Landvik et al. BMC Proceedings 2010, 4(Suppl 2):O3
http://www.biomedcentral.com/1753-6561/4/S2/O3
© 2010 Haugen et al; licensee BioMed Central Ltd.


Gene variants and lung cancer risk

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Gene variants and lung cancer risk

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