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Article first published online: 8 OCT 2012
Published 2012 American Cancer Society
Volume 118, Issue 22, pages 5630–5636, 15 November 2012
How to Cite
Shiels, M. S., Engels, E. A., Shi, J., Landi, M. T., Albanes, D., Chatterjee, N., Chanock, S. J., Caporaso, N. E. and Chaturvedi, A. K. (2012), Genetic variation in innate immunity and inflammation pathways associated with lung cancer risk . Cancer, 118: 5630–5636. doi: 10.1002/cncr.27605
For the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, we thank Drs. Christine Berg and Philip Prorok, Division of Cancer Prevention, National Cancer Institute (NCI); the Screening Center investigators and staff of the PLCO Cancer Screening Trial; Mr. Tom Riley and staff, Information Management Services, Inc.; Ms. Barbara O'Brien and staff, Westat, Inc.; Mr. Tim Sheehy and staff, DNA Extraction and Staging Laboratory, Science Applications International Corporation (SAIC)-Frederick, Inc.; and Ms. Jackie King and staff, BioReliance, Inc. Most important, we acknowledge the study participants for their contributions to making this study possible.
For the NCI genome-wide association study, we thank the participants and collaborators of the Environment and Genetics in Lung Cancer Etiology (EAGLE), Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC), PLCO, and Cancer Prevention Study-II (CPS-II) Nutrition Cohort studies; the staff of the Core Genotyping Facility—specifically Amy Hutchinson, Aurelie Vogt, Kevin Jacobs, and Zhaoming Wang; the National Center for Biotechnology for assistance with data cleaning; Justin Paschall and Mike Feolo for data manipulation; and Adam Risch, Bill Wheeler, and Sihui Zhao of Information Management Services, Inc. for database support. *This article is US Government work and, as such, is in the public domain in the United States of America.
This article is US Government work and, as such, is in the public domain in the United States of America.
- Issue published online: 30 OCT 2012
- Article first published online: 8 OCT 2012
- Manuscript Accepted: 22 MAR 2012
- Manuscript Revised: 20 MAR 2012
- Manuscript Received: 13 JAN 2012
- lung cancer;
Pulmonary inflammation may contribute to lung cancer etiology. The authors conducted a broad evaluation of the association of single nucleotide polymorphisms (SNPs) in innate immunity and inflammation pathways with lung cancer risk and conducted comparisons with a lung cancer genome-wide association study (GWAS).
In total, 378 patients with lung cancer (cases) and a group of 450 controls from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial were included. A proprietary oligonucleotide pool assay was used to genotype 1429 SNPs. Odds ratios and 95% confidence intervals were estimated for each SNP, and P values for trend (Ptrend) were calculated. For statistically significant SNPs (Ptrend < .05), the results were replicated with genotyped or imputed SNPs in the GWAS, and P values were adjusted for multiple testing.
In the PLCO analysis, a significant association was observed between lung cancer and 81 SNPs located in 44 genes (Ptrend < .05). Of these 81 SNPS, there was evidence for confirmation in the GWAS for 10 SNPs. However, after adjusting for multiple comparisons, the only SNP that retained a significant association with lung cancer in the replication phase was reference SNP rs4648127 (nuclear factor of kappa light polypeptide gene enhancer of B-cells 1 [NFKB1]) (multiple testing-adjusted Ptrend = .02). The cytosine-thymine (CT)/TT genotype of NFKB1 was associated with reduced odds of lung cancer in the PLCO study (odds ratio, 0.56; 95% confidence interval, 0.37-0.86) and the in the GWAS (odds ratio, 0.79; 95% confidence interval, 0.69-0.90).
A significant association was observed between a variant in the NFKB1 gene and the risk of lung cancer. The current findings add to evidence implicating inflammation and immunity in lung cancer etiology. Cancer 2012. Published 2012 by the American Cancer Society.