Skip Navigation



Carcinogenesis Advance Access published online on May 21, 2009
Carcinogenesis, doi:10.1093/carcin/bgp122
This Article
Right arrow Advance Access manuscript (PDF)
Right arrow Supplementary Data
Right arrow All Versions of this Article:
30/7/1186    most recent
bgp122v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Landvik, N. E.
Right arrow Articles by Zienolddiny, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Landvik, N. E.
Right arrow Articles by Zienolddiny, S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

A specific interleukin-1B haplotype correlates with high levels of IL1B mRNA in the lung and increased risk of non-small cell lung cancer

Nina E. Landvik1, Kent Hart1, Vidar Skaug1, Lodve B. Stangeland2, Aage Haugen1 and Shanbeh Zienolddiny1,*

1 Section of Toxicology, Department of Chemical and Biological Work Environment, National Institute of Occupational Health, Oslo, Norway
2 Haukeland University Hospital, Bergen, Norway

* To whom correspondence should be addressed. Tel: +47 2319 5284; Fax: +47 2319 5204; E-mail; Shan.zienolddiny{at}stami.no

Epidemiological evidence suggests a relationship between chronic inflammation and lung cancer. Inflammation in the lung may be modulated by host genetic factors such as polymorphisms in inflammatory genes. Identification of polymorphisms in inflammatory genes may help understanding interindividual differences in susceptibility to lung cancer. We have investigated single nucleotide polymorphisms and their haplotypes in the regulatory region of IL1B gene in association to non-small cell lung cancer (NSCLC) risk. Our previous work showed that two promoter SNPs C-511T and T-31C modulated NSCLC risk. In the present study, we show that G-3893A and G-1464C located in the enhancer region of the IL1B gene may also affect this risk, with odds for developing NSCLC being 0.69 (95% CI, 0.52 – 0.92) for -3893 A-allele and 0.63 (95% CI, 0.47 – 0.83) for -1464 C-allele. The associations were particularly prominent in patients with TP53 mutations in the tumor. Inference of the haplotype structures showed that -3893 G, -1464 G, -511 C and -31 T formed a specific haplotype (GGCT) with near complete linkage disequilibrium in lung cancer patients, but not in controls. Furthermore, the risk haplotype (GGCT) was present in 65% of cases compared to 36% of controls. Quantitative analysis of RNA in normal lung tissue of the patients showed that the risk haplotype was correlated with significantly higher IL1B mRNA levels compared to the non-risk haplotype (ACTC). These data suggest that a specific IL1B haplotype associated with increased IL1B gene expression increases the risk of NSCLC.

Key Words: Lung cancer • NSCLC • carcinogenesis • inflammation • IL1B

Received April 2, 2009; revised May 8, 2009; accepted May 11, 2009.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.