Gene by Environment Investigation of Incident Lung Cancer Risk in African-Americans.
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 articleSubject
African-AmericansEnvironment
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
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https://hdl.handle.net/10161/15151Published Version (Please cite this version)
10.1016/j.ebiom.2016.01.002Publication 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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Show full item recordScholars@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/
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
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