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Gene by Environment Investigation of Incident Lung Cancer Risk in African-Americans
- 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;
- Brown, W Mark;
- 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
- et al.
Published Web Location
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4776066/No data is associated with this publication.
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.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.