Gene by Environment Investigation of Incident Lung Cancer Risk in African-Americans.
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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.
Single Nucleotide Polymorphisms
Chromosomes, Human, Pair 15
Nerve Tissue Proteins
Polymorphism, Single Nucleotide
Published Version (Please cite this version)10.1016/j.ebiom.2016.01.002
Publication InfoAmos, CI; Assimes, T; Bergen, AW; Brown, W Mark; David, Sean P; Desai, M; ... Yang, 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 http://hdl.handle.net/10161/15151.
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Associate Professor of Neurosurgery
Dr. Walsh’s research program focuses on genetic and epigenetic factors contributing to cancer predisposition in children and adults, with a special interest in brain tumors. This research is informed by both epidemiology and anthropological genetics, with computational work stressing statistical methodologies for “gene hunting” (e.g. GWAS, fine-mapping, admixture mapping, whole-genome sequencing). The laboratory engages in functional genomics research, investigating the biologi