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

dc.contributor.author

David, Sean P

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Wang, Ange

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Kapphahn, Kristopher

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Hedlin, Haley

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Desai, Manisha

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Henderson, Michael

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Yang, Lingyao

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Walsh, Kyle M

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Schwartz, Ann G

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Wiencke, John K

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Spitz, Margaret R

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Wenzlaff, Angela S

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Wrensch, Margaret R

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Eaton, Charles B

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Furberg, Helena

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Mark Brown, W

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Goldstein, Benjamin A

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Assimes, Themistocles

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Tang, Hua

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Kooperberg, Charles L

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Quesenberry, Charles P

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Tindle, Hilary

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Patel, Manali I

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Amos, Christopher I

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Bergen, Andrew W

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Swan, Gary E

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Stefanick, Marcia L

dc.coverage.spatial

Netherlands

dc.date.accessioned

2017-08-01T17:42:39Z

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2017-08-01T17:42:39Z

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2016-02

dc.description.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.

dc.identifier

https://www.ncbi.nlm.nih.gov/pubmed/26981579

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S2352-3964(16)30001-9

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2352-3964

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https://hdl.handle.net/10161/15151

dc.language

eng

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Elsevier BV

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EBioMedicine

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10.1016/j.ebiom.2016.01.002

dc.subject

African-Americans

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Environment

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Genetics

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Lung Cancer

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Single Nucleotide Polymorphisms

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Smoking

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rs2036527

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African Americans

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Case-Control Studies

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Chromosomes, Human, Pair 15

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Female

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Gene-Environment Interaction

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Genes, Modifier

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Humans

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Lung Neoplasms

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Male

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Nerve Tissue Proteins

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Polymorphism, Single Nucleotide

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Receptors, Nicotinic

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Smoking

dc.title

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

dc.type

Journal article

duke.contributor.orcid

Walsh, Kyle M|0000-0002-5879-9981

duke.contributor.orcid

Goldstein, Benjamin A|0000-0001-5261-3632

pubs.author-url

https://www.ncbi.nlm.nih.gov/pubmed/26981579

pubs.begin-page

153

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161

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Basic Science Departments

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Biostatistics & Bioinformatics

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Clinical Science Departments

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Duke

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Neurosurgery

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School of Medicine

pubs.publication-status

Published online

pubs.volume

4

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