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Gene by Environment Investigation of Incident Lung Cancer Risk in African-Americans.

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Date
2016-02
Authors
David, Sean P
Wang, Ange
Kapphahn, Kristopher
Hedlin, Haley
Desai, Manisha
Henderson, Michael
Yang, Lingyao
Walsh, Kyle M
Schwartz, Ann G
Wiencke, John K
Spitz, Margaret R
Wenzlaff, Angela S
Wrensch, Margaret R
Eaton, Charles B
Furberg, Helena
Mark Brown, W
Goldstein, Benjamin A
Assimes, Themistocles
Tang, Hua
Kooperberg, Charles L
Quesenberry, Charles P
Tindle, Hilary
Patel, Manali I
Amos, Christopher I
Bergen, Andrew W
Swan, Gary E
Stefanick, Marcia L
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(27 total)
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Abstract
BACKGROUND: Genome-wide association studies have identified polymorphisms linked to both smoking exposure and risk of lung cancer. The degree to which lung cancer risk is driven by increased smoking, genetics, or gene-environment interactions is not well understood. METHODS: We analyzed associations between 28 single nucleotide polymorphisms (SNPs) previously associated with smoking quantity and lung cancer in 7156 African-American females in the Women's Health Initiative (WHI), then analyzed main effects of top nominally significant SNPs and interactions between SNPs, cigarettes per day (CPD) and pack-years for lung cancer in an independent, multi-center case-control study of African-American females and males (1078 lung cancer cases and 822 controls). FINDINGS: Nine nominally significant SNPs for CPD in WHI were associated with incident lung cancer (corrected p-values from 0.027 to 6.09 × 10(-5)). CPD was found to be a nominally significant effect modifier between SNP and lung cancer for six SNPs, including CHRNA5 rs2036527[A](betaSNP*CPD = - 0.017, p = 0.0061, corrected p = 0.054), which was associated with CPD in a previous genome-wide meta-analysis of African-Americans. INTERPRETATION: These results suggest that chromosome 15q25.1 variants are robustly associated with CPD and lung cancer in African-Americans and that the allelic dose effect of these polymorphisms on lung cancer risk is most pronounced in lighter smokers.
Type
Journal article
Subject
African-Americans
Environment
Genetics
Lung Cancer
Single Nucleotide Polymorphisms
Smoking
rs2036527
African Americans
Case-Control Studies
Chromosomes, Human, Pair 15
Female
Gene-Environment Interaction
Genes, Modifier
Humans
Lung Neoplasms
Male
Nerve Tissue Proteins
Polymorphism, Single Nucleotide
Receptors, Nicotinic
Smoking
Permalink
https://hdl.handle.net/10161/15151
Published Version (Please cite this version)
10.1016/j.ebiom.2016.01.002
Publication Info
David, Sean P; Wang, Ange; Kapphahn, Kristopher; Hedlin, Haley; Desai, Manisha; Henderson, Michael; ... Stefanick, Marcia L (2016). Gene by Environment Investigation of Incident Lung Cancer Risk in African-Americans. EBioMedicine, 4. pp. 153-161. 10.1016/j.ebiom.2016.01.002. Retrieved from https://hdl.handle.net/10161/15151.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Benjamin Alan Goldstein

Associate Professor of Biostatistics & Bioinformatics
I study the meaningful use of Electronic Health Records data. My research interests sit at the intersection of biostatistics, biomedical informatics, machine learning and epidemiology. I collaborate with researchers both locally at Duke as well as nationally. I am interested in speaking with any students, methodologistis or collaborators interested in EHR data.Please find more information at: https://sites.duke.edu/bgoldstein/
Walsh

Kyle Walsh

Associate Professor of Neurosurgery
Dr. Walsh is Associate Professor of Neurosurgery and Pathology, Director of the Division of Neuro-epidemiology, and a Senior Fellow in the Duke Center for the Study of Aging and Human Development. He leads Duke’s Neuro-epidemiology Lab, which integrates bench science with statistical methods to study the neurobiology of glial senescence and gliomagenesis. This research interrogates human genomic and epigenomic profiles to identify both heritable and modifiable factors that contribute to ne
Alphabetical list of authors with Scholars@Duke profiles.
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