Area 1: Discovery and validation of genetic factors influencing lung cancer risk. While several genetic loci have been identified by genome-wide scans, we hypothesize that additional loci influencing risk for lung cancer development can be identified by joint analyses in which data from multiple studies are combined. In addition, combining genotypic data will allow analysis according to demographic and clinical parameters, and permit studies to identify gene-gene and gene-environment factors that specifically increase lung cancer risk. Genetic loci that have been identified by these pooled analyses warrant further follow-up in world-wide populations to evaluate the extent that the same or other SNPs associate with lung cancer risk. Finally, follow-up studies with additfonal fine mapping and resequencing of selected populations, together with functionalanalyses, will help to identify the specific causal factors that influence cancer risk. In area 1 we are using a large and diverse population to identify genetic risk factors for lung cancer. First we will integrate 8 genome wide studies to form a pooled sample of over 13000 lung cancer cases and 25000 controls. We will perform stratified analyses to identify genes that only affect subsets of lung cancer such as early onset, and histology specific effects. We will also seek to discover significant predictors of lung cancer risk using gene-environment and gene-gene interaction analyses. Pathway analyses will also.be performed to assist in gene discovery. We will perform flne mapping and initial replication of these findings by genotyping an additional 6000 cases and 6000 controls of African-American, Chinese and Caucasian ancestry. We will finally validate our findings in an additional collection of 6000 lung cancer cases and 6000 controls. We anticipate that our studies will allow an exhaustive search of genes that have either main effects on lung cancer risk or that increase risk in combination with genetic or environmental cofactors. Our findings will be used for further functional studies in area 2 of the U19 response and epidemiological characterization in area 3 of the U19 response.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19CA148127-04
Application #
8550774
Study Section
Special Emphasis Panel (ZCA1-SRLB-4)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2013
Total Cost
$1,110,305
Indirect Cost
$49,611
Name
Dartmouth College
Department
Type
DUNS #
041027822
City
Hanover
State
NH
Country
United States
Zip Code
03755
David, Sean P; Wang, Ange; Kapphahn, Kristopher et al. (2016) Gene by Environment Investigation of Incident Lung Cancer Risk in African-Americans. EBioMedicine 4:153-61
Wang, Zhaoming; Seow, Wei Jie; Shiraishi, Kouya et al. (2016) Meta-analysis of genome-wide association studies identifies multiple lung cancer susceptibility loci in never-smoking Asian women. Hum Mol Genet 25:620-9
Scarbrough, Peter M; Weber, Rachel Palmieri; Iversen, Edwin S et al. (2016) A Cross-Cancer Genetic Association Analysis of the DNA Repair and DNA Damage Signaling Pathways for Lung, Ovary, Prostate, Breast, and Colorectal Cancer. Cancer Epidemiol Biomarkers Prev 25:193-200
Lieberman, Rachel; Xiong, Donghai; James, Michael et al. (2016) Functional characterization of RAD52 as a lung cancer susceptibility gene in the 12p13.33 locus. Mol Carcinog 55:953-63
Puskás, László G; Mán, Imola; Szebeni, Gabor et al. (2016) Novel Anti-CRR9/CLPTM1L Antibodies with Antitumorigenic Activity Inhibit Cell Surface Accumulation, PI3K Interaction, and Survival Signaling. Mol Cancer Ther 15:985-97
Chen, Li-Shiun; Baker, Timothy; Hung, Rayjean J et al. (2016) Genetic Risk Can Be Decreased: Quitting Smoking Decreases and Delays Lung Cancer for Smokers With High and Low CHRNA5 Risk Genotypes - A Meta-Analysis. EBioMedicine 11:219-226
Kang, Xiaozheng; Liu, Hongliang; Onaitis, Mark W et al. (2016) Polymorphisms of the centrosomal gene (FGFR1OP) and lung cancer risk: a meta-analysis of 14,463 cases and 44,188 controls. Carcinogenesis 37:280-9
Kachuri, Linda; Amos, Christopher I; McKay, James D et al. (2016) Fine mapping of chromosome 5p15.33 based on a targeted deep sequencing and high density genotyping identifies novel lung cancer susceptibility loci. Carcinogenesis 37:96-105
Karami, Sara; Han, Younghun; Pande, Mala et al. (2016) Telomere structure and maintenance gene variants and risk of five cancer types. Int J Cancer 139:2655-2670
Patel, Yesha M; Park, Sunghim L; Han, Younghun et al. (2016) Novel Association of Genetic Markers Affecting CYP2A6 Activity and Lung Cancer Risk. Cancer Res 76:5768-5776

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