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Grant Details

Grant Number: 7R01CA149462-05 Interpret this number
Primary Investigator: Gorlova, Olga
Organization: Dartmouth College
Project Title: A Genomewide Study of Lung Cancer in Never Smokers
Fiscal Year: 2014


DESCRIPTION (provided by applicant): Lung cancer remains the leading cause of cancer death, killing more patients than breast, colon, and prostate cancers combined. Although tobacco smoke is the predominant risk factor for development of lung cancer, some patients develop the disease without a history of tobacco smoking. About 10 - 15% of all lung cancers occur in lilfetime never smokers. This figure will increase as the proportion of never smokers increases in the population. Even at present rates, lung cancer in never smokers, if considered a separate disease, is 7th to 9th top cause of cancer death. The growing number of never smokers in the USA and other countries emphasizes the importance of understanding the epidemiology and biology underlying lung cancer in this group. Epidemiological, molecular and clinical data suggest that molecular mechanisms of lung cancer may differ in smokers and nonsmokers, making lung cancer in never smokers a different disease compared to the lung cancer in smokers. The genetic epidemiology of lung cancer in never smokers has not been well explored, largely because of difficulties in accruing the needed sample size for association studies. We propose a multicenter (total 22 sites from North America, Israel, and Europe) genomewide association study of lung cancer in never smokers with the following specific aims: Aim 1: Discovery phase: To identify candidate SNPs influencing the risk for lung cancer in never smokers. This phase will include 1553 never smoker lung cancer cases and 1553 controls matched on age, gender, and study site. Aim 2: Replication phase: To perform replication analysis of significant SNPs identified in the Discovery phase, using an independent set of cases and controls from International Lung Cancer Consortium (ILCCO) studies. There will be 1581 independent cases and 1581 matched controls in this phase. Aim 3: To identify and explore pathways associated with the risk of lung cancer in never smokers. To explore the effects of gene-gene and gene-environment interactions on lung cancer risk in never smokers. This will be the first GWAS aiming at identifying the genetic control of susceptibility to lung cancer in Caucasian never smokers. We will combine the available resources from the multiple sites to achieve the sample size sufficient for this study. The study will identify genetic architecture of the predisposition to the lung cancer in never smokers.


Lung Cancer Risk in Never-Smokers of European Descent is Associated With Genetic Variation in the 5p15.33 TERT-CLPTM1Ll Region.
Authors: Hung R.J. , Spitz M.R. , Houlston R.S. , Schwartz A.G. , Field J.K. , Ying J. , Li Y. , Han Y. , Ji X. , Chen W. , et al. .
Source: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2019 Aug; 14(8), p. 1360-1369.
EPub date: 2019-04-19.
PMID: 31009812
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Gene characteristics predicting missense, nonsense and frameshift mutations in tumor samples.
Authors: Gorlov I.P. , Pikielny C.W. , Frost H.R. , Her S.C. , Cole M.D. , Strohbehn S.D. , Wallace-Bradley D. , Kimmel M. , Gorlova O.Y. , Amos C.I. .
Source: BMC bioinformatics, 2018-11-19; 19(1), p. 430.
EPub date: 2018-11-19.
PMID: 30453881
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Downstream targets of GWAS-detected genes for breast, lung, and prostate and colon cancer converge to G1/S transition pathway.
Authors: Gorlova O.Y. , Demidenko E.I. , Amos C.I. , Gorlov I.P. .
Source: Human molecular genetics, 2017-04-15; 26(8), p. 1465-1471.
PMID: 28334950
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A Novel Pathway-Based Approach Improves Lung Cancer Risk Prediction Using Germline Genetic Variations.
Authors: Qian D.C. , Han Y. , Byun J. , Shin H.R. , Hung R.J. , McLaughlin J.R. , Landi M.T. , Seminara D. , Amos C.I. .
Source: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2016 Aug; 25(8), p. 1208-15.
EPub date: 2016-05-24.
PMID: 27222311
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Informed genome-wide association analysis with family history as a secondary phenotype identifies novel loci of lung cancer.
Authors: Poirier J.G. , Brennan P. , McKay J.D. , Spitz M.R. , Bickeböller H. , Risch A. , Liu G. , Le Marchand L. , Tworoger S. , McLaughlin J. , et al. .
Source: Genetic epidemiology, 2015 Mar; 39(3), p. 197-206.
EPub date: 2015-01-19.
PMID: 25644374
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Genes with a large intronic burden show greater evolutionary conservation on the protein level.
Authors: Gorlova O. , Fedorov A. , Logothetis C. , Amos C. , Gorlov I. .
Source: BMC evolutionary biology, 2014-03-16; 14(1), p. 50.
EPub date: 2014-03-16.
PMID: 24629165
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Modeling the natural history and detection of lung cancer based on smoking behavior.
Authors: Chen X. , Foy M. , Kimmel M. , Gorlova O.Y. .
Source: PloS one, 2014; 9(4), p. e93430.
EPub date: 2014-04-04.
PMID: 24705368
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Associations between dietary intake of choline and betaine and lung cancer risk.
Authors: Ying J. , Rahbar M.H. , Hallman D.M. , Hernandez L.M. , Spitz M.R. , Forman M.R. , Gorlova O.Y. .
Source: PloS one, 2013; 8(2), p. e54561.
EPub date: 2013-02-01.
PMID: 23383301
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Genome-wide association study reveals novel genetic determinants of DNA repair capacity in lung cancer.
Authors: Wang L.E. , Gorlova O.Y. , Ying J. , Qiao Y. , Weng S.F. , Lee A.T. , Gregersen P.K. , Spitz M.R. , Amos C.I. , Wei Q. .
Source: Cancer research, 2013-01-01; 73(1), p. 256-64.
EPub date: 2012-10-29.
PMID: 23108145
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Beyond comparing means: the usefulness of analyzing interindividual variation in gene expression for identifying genes associated with cancer development.
Authors: Gorlov I.P. , Byun J. , Zhao H. , Logothetis C.J. , Gorlova O.Y. .
Source: Journal of bioinformatics and computational biology, 2012 Apr; 10(2), p. 1241013.
PMID: 22809348
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Derived SNP alleles are used more frequently than ancestral alleles as risk-associated variants in common human diseases.
Authors: Gorlova O.Y. , Ying J. , Amos C.I. , Spitz M.R. , Peng B. , Gorlov I.P. .
Source: Journal of bioinformatics and computational biology, 2012 Apr; 10(2), p. 1241008.
PMID: 22809343
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Initial medical attention on patients with early-stage non-small cell lung cancer.
Authors: Chen X. , Gorlov I.P. , Ying J. , Merriman K.W. , Kimmel M. , Lu C. , Reyes-Gibby C.C. , Gorlova O.Y. .
Source: PloS one, 2012; 7(3), p. e32644.
EPub date: 2012-03-07.
PMID: 22412901
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Variants in inflammation genes are implicated in risk of lung cancer in never smokers exposed to second-hand smoke.
Authors: Spitz M.R. , Gorlov I.P. , Amos C.I. , Dong Q. , Chen W. , Etzel C.J. , Gorlova O.Y. , Chang D.W. , Pu X. , Zhang D. , et al. .
Source: Cancer discovery, 2011 Oct; 1(5), p. 420-9.
EPub date: 2011-08-25.
PMID: 22586632
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Adjusting a cancer mortality-prediction model for disease status-related eligibility criteria.
Authors: Foy M. , Chen X. , Kimmel M. , Gorlova O.Y. .
Source: BMC medical research methodology, 2011-05-11; 11, p. 64.
EPub date: 2011-05-11.
PMID: 21569346
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Dietary patterns affect lung cancer risk in never smokers.
Authors: Gorlova O.Y. , Weng S.F. , Hernandez L. , Spitz M.R. , Forman M.R. .
Source: Nutrition and cancer, 2011; 63(6), p. 842-9.
EPub date: 2011-07-20.
PMID: 21774612
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