Three new lung cancer genetic biomarkers identified
In a large genome-wide association analysis, researchers identify novel gene-smoking interactions in lung cancer development, providing new candidate biomarkers and further closing the gap between heritability and lung cancer
- Date:
- October 28, 2017
- Source:
- Dartmouth-Hitchcock Medical Center
- Summary:
- SNPs (single-nucleotide polymorphisms) are variations in our DNA that determine our susceptibility to developing some diseases. Using the largest genome-wide SNP-smoking interaction analysis reported for lung cancer, a research team has identified three novel SNPs. The results from their study reinforce that gene-smoking interactions play important roles in the etiology of lung cancer and account for part of the missing heritability of this disease.
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SNPs (single-nucleotide polymorphisms) are variations in our DNA that determine our susceptibility to developing some diseases. Using the largest genome-wide SNP-smoking interaction analysis reported for lung cancer, a research team led by Dartmouth's Norris Cotton Cancer Center's Yafang Li, PhD, has identified three novel SNPs. The results from their study reinforce that gene-smoking interactions play important roles in the etiology of lung cancer and account for part of the missing heritability of this disease.
Both environmental and genetic risk factors contribute to development of lung cancer. Tobacco smoking is the most well-known environmental risk factor associated with lung cancer. A Dartmouth research team led by Yafang Li, PhD, has conducted a study to display that gene-smoking interactions play important roles in the etiology of lung cancer.
In their study, three novel SNPs (single-nucleotide polymorphisms), or variations in our DNA that underlie our susceptibility to developing disease, were identified in the interaction analysis, including two SNPs for non-small cell lung cancer risk and one SNP for squamous cell lung cancer risk. The three identified novel SNPs provide potential candidate biomarkers for lung cancer risk screening and intervention. The team's findings, "Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population," have been published in Carcinogenesis.
The genotype and phenotype data used in this analysis came from OncoArray Consortium. "Genome-wide interaction scanning remains a challenge as most genome-wide association studies are designed for main effect association analysis and have limited power for interaction analysis," said Li. "This study is by far the largest genome-wide SNP-smoking interaction analysis reported for lung cancer. We also adopted a two-step strategy in the analysis to reduce the power loss from ordinary gene-environment interaction analysis."
The three SNPs, identified in the team's study, stratify lung cancer risk by smoking behavior. These three SNPs can be potential biomarkers used to improve the precision to which researchers can categorize an individual's risk of lung cancer disease by smoking behavior, which are helpful for individualized prognosis and prediction of treatment plan.
While this reported study was restricted to a Caucasian population and the results may not be generalized to other ethnicities because of the different genetic backgrounds, the team aims to further test the identified interaction effect using genotype from other populations. "The limited overlap between discovery genotype and replication genotype may have reduced the power in our validation study," says Li. "We believe as more genotype data becomes available in the future we can discover more important gene-smoking interaction in lung cancer disease."
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Materials provided by Dartmouth-Hitchcock Medical Center. Note: Content may be edited for style and length.
Journal Reference:
- Yafang Li, Xiangjun Xiao, Younghun Han, Olga Gorlova, David Qian, Natasha Leighl, Jakob S Johansen, Matt Barnett, Chu Chen, Gary Goodman, Angela Cox, Fiona Taylor, Penella Woll, H -Erich Wichmann, Judith Manz, Thomas Muley, Angela Risch, Albert Rosenberger, Susanne M Arnold, Eric B Haura, Ciprian Bolca, Ivana Holcatova, Vladimir Janout, Milica Kontic, Jolanta Lissowska, Anush Mukeria, Simona Ognjanovic, Tadeusz M Orlowski, Ghislaine Scelo, Beata Swiatkowska, David Zaridze, Per Bakke, Vidar Skaug, Shanbeh Zienolddiny, Eric J Duell, Lesley M Butler, Richard Houlston, María Soler Artigas, Kjell Grankvist, Mikael Johansson, Frances A Shepherd, Michael W Marcus, Hans Brunnström, Jonas Manjer, Olle Melander, David C Muller, Kim Overvad, Antonia Trichopoulou, Rosario Tumino, Geoffrey Liu, Stig E Bojesen, Xifeng Wu, Loic Le Marchand, Demetrios Albanes, Heike Bickeböller, Melinda C Aldrich, William S Bush, Adonina Tardon, Gad Rennert, M Dawn Teare, John K Field, Lambertus A Kiemeney, Philip Lazarus, Aage Haugen, Stephen Lam, Matthew B Schabath, Angeline S Andrew, Pier Alberto Bertazzi, Angela C Pesatori, David C Christiani, Neil Caporaso, Mattias Johansson, James D McKay, Paul Brennan, Rayjean J Hung, Christopher I Amos. Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population. Carcinogenesis, 2017; DOI: 10.1093/carcin/bgx113
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