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Grant Details

Grant Number: 1R01CA166672-01A1 Interpret this number
Primary Investigator: Asgari, Maryam
Organization: Kaiser Foundation Research Institute
Project Title: Genome-Wide Association Study of Cutaneous Squamous Cell Carcinoma
Fiscal Year: 2013
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Abstract

DESCRIPTION (provided by applicant): Cutaneous squamous cell carcinoma (SCC) is the second most common cancer in America, with over 700,000 cases diagnosed annually, and its incidence is on the rise. Despite the large population affected and resultant burden of disease, little is known about genetic determinants of SCCs. There are no published genome-wide association studies (GWAS) examining single nucleotide polymorphism (SNP) variants associated with SCC risk. The lack of published findings may be due, in part, to the fact that cutaneous SCCs are not reportable malignancies, and are therefore difficult to reliably identify. The electronic pathology databases at Kaiser Permanente Northern California (KNPC) overcome that barrier, and have been used to capture all biopsy-proven cutaneous SCCs from 1997 onward in a validated SCC registry. This project utilizes existing genetic data on over 675,000 SNPs from a large, well-characterized cohort of the Research Program on Genes, Environment and Health (RPGEH). The RPGEH has also collected comprehensive data including information on demographic and environmental variables on its cohort members. Using the unique resources of the RPGEH combined with the SCC Registry, we aim to perform a GWAS to identify SNP sequence variants associated with SCC risk on 77,578 non-Hispanic white RPGEH members, 5,953 of whom go on to develop at least one post-enrollment SCC. We will also test for interactions with established SCC risk factors, including pigmentation, gender, smoking, and actinic keratosis (a clinical marker for chronic ultraviolet light exposure). Furthermore, we will determine whether our identified SNP associations are stronger in subjects with multiple primary SCCs. In addition, we will evaluate whether there is any variation in SNP effects by tumor characteristics. Finally, we will compare our SNPs with those previously identified for BCCs and melanomas from published GWAS to attempt to identify genetic loci associated with skin cancer risk. Ultimately, we seek to improve our understanding of cutaneous SCCs and to identify mechanisms accounting for increased inherited susceptibility. PUBLIC HEALTH RELEVANCE: The goal of this proposal is conduct a genome-wide association study in a large cohort of approximately 77,578 Kaiser Permanente Northern California members to identify genetic loci associated with risk of cutaneous squamous cell carcinoma (SCC). We will utilize Kaiser's rich electronic databases to look for gene- environment interactions, and evaluate the strength of identified associations with tumor variables. We will also compare our identified genetic loci to previously identified loci for other skin cancers. Our goal is to improve understanding of the mechanisms accounting for increased inherited susceptibility to SCC.

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Publications

Nanog1 in NTERA-2 and recombinant NanogP8 from somatic cancer cells adopt multiple protein conformations and migrate at multiple M.W species.
Authors: Liu B, Badeaux MD, Choy G, Chandra D, Shen I, Jeter CR, Rycaj K, Lee CF, Person MD, Liu C, Chen Y, Shen J, Jung SY, Qin J, Tang DG
Source: PLoS One, 2014;9(3), p. e90615.
EPub date: 2014 Mar 5.
PMID: 24598770
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In vivo functional studies of tumor-specific retrogene NanogP8 in transgenic animals.
Authors: Badeaux MA, Jeter CR, Gong S, Liu B, Suraneni MV, Rundhaug J, Fischer SM, Yang T, Kusewitt D, Tang DG
Source: Cell Cycle, 2013 Aug 1;12(15), p. 2395-408.
EPub date: 2013 Jun 26.
PMID: 23839044
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Trans-tail regulation of MLL4-catalyzed H3K4 methylation by H4R3 symmetric dimethylation is mediated by a tandem PHD of MLL4.
Authors: Dhar SS, Lee SH, Kan PY, Voigt P, Ma L, Shi X, Reinberg D, Lee MG
Source: Genes Dev, 2012 Dec 15;26(24), p. 2749-62.
PMID: 23249737
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A high positive lymph node ratio is associated with distant recurrence after surgical resection of ampullary carcinoma.
Authors: Roland CL, Katz MH, Gonzalez GM, Pisters PW, Vauthey JN, Wolff RA, Crane CH, Lee JE, Fleming JB
Source: J Gastrointest Surg, 2012 Nov;16(11), p. 2056-63.
EPub date: 2012 Aug 23.
PMID: 22914983
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The PSA(-/lo) prostate cancer cell population harbors self-renewing long-term tumor-propagating cells that resist castration.
Authors: Qin J, Liu X, Laffin B, Chen X, Choy G, Jeter CR, Calhoun-Davis T, Li H, Palapattu GS, Pang S, Lin K, Huang J, Ivanov I, Li W, Suraneni MV, Tang DG
Source: Cell Stem Cell, 2012 May 4;10(5), p. 556-69.
PMID: 22560078
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Violation of the rectus complex is not a contraindication to component separation for abdominal wall reconstruction.
Authors: Garvey PB, Bailey CM, Baumann DP, Liu J, Butler CE
Source: J Am Coll Surg, 2012 Feb;214(2), p. 131-9.
EPub date: 2011 Dec 9.
PMID: 22169002
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Methodologies in assaying prostate cancer stem cells.
Authors: Li H, Jiang M, Honorio S, Patrawala L, Jeter CR, Calhoun-Davis T, Hayward SW, Tang DG
Source: Methods Mol Biol, 2009;568, p. 85-138.
PMID: 19582423
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Functional evidence that the self-renewal gene NANOG regulates human tumor development.
Authors: Jeter CR, Badeaux M, Choy G, Chandra D, Patrawala L, Liu C, Calhoun-Davis T, Zaehres H, Daley GQ, Tang DG
Source: Stem Cells, 2009 May;27(5), p. 993-1005.
PMID: 19415763
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Abnormal differentiation, hyperplasia and embryonic/perinatal lethality in BK5-T/t transgenic mice.
Authors: Chen X, Schneider-Broussard R, Hollowell D, McArthur M, Jeter CR, Benavides F, DiGiovanni J, Tang DG
Source: Differentiation, 2009 Mar;77(3), p. 324-34.
EPub date: 2008 Nov 21.
PMID: 19272531
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Critical and distinct roles of p16 and telomerase in regulating the proliferative life span of normal human prostate epithelial progenitor cells.
Authors: Bhatia B, Jiang M, Suraneni M, Patrawala L, Badeaux M, Schneider-Broussard R, Multani AS, Jeter CR, Calhoun-Davis T, Hu L, Hu J, Tsavachidis S, Zhang W, Chang S, Hayward SW, Tang DG
Source: J Biol Chem, 2008 Oct 10;283(41), p. 27957-72.
EPub date: 2008 Jul 28.
PMID: 18662989
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PC3 human prostate carcinoma cell holoclones contain self-renewing tumor-initiating cells.
Authors: Li H, Chen X, Calhoun-Davis T, Claypool K, Tang DG
Source: Cancer Res, 2008 Mar 15;68(6), p. 1820-5.
PMID: 18339862
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Hierarchical organization of prostate cancer cells in xenograft tumors: the CD44+alpha2beta1+ cell population is enriched in tumor-initiating cells.
Authors: Patrawala L, Calhoun-Davis T, Schneider-Broussard R, Tang DG
Source: Cancer Res, 2007 Jul 15;67(14), p. 6796-805.
PMID: 17638891
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Prostate cancer stem/progenitor cells: identification, characterization, and implications.
Authors: Tang DG, Patrawala L, Calhoun T, Bhatia B, Choy G, Schneider-Broussard R, Jeter C
Source: Mol Carcinog, 2007 Jan;46(1), p. 1-14.
PMID: 16921491
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Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells.
Authors: Patrawala L, Calhoun T, Schneider-Broussard R, Li H, Bhatia B, Tang S, Reilly JG, Chandra D, Zhou J, Claypool K, Coghlan L, Tang DG
Source: Oncogene, 2006 Mar 16;25(12), p. 1696-708.
PMID: 16449977
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Acquisition of anoikis resistance in human osteosarcoma cells does not alter sensitivity to chemotherapeutic agents.
Authors: Díaz-Montero CM, McIntyre BW
Source: BMC Cancer, 2005 Apr 13;5, p. 39.
EPub date: 2005 Apr 13.
PMID: 15829011
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Acquisition of anoikis resistance in human osteosarcoma cells.
Authors: Díaz-Montero CM, McIntyre BW
Source: Eur J Cancer, 2003 Nov;39(16), p. 2395-402.
PMID: 14556933
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Human breast cancer MCF-7 cell line contains inherently drug-resistant subclones with distinct genotypic and phenotypic features.
Authors: Devarajan E, Chen J, Multani AS, Pathak S, Sahin AA, Mehta K
Source: Int J Oncol, 2002 May;20(5), p. 913-20.
PMID: 11956583
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Radiation-induced cell death in the mouse testis: relationship to apoptosis.
Authors: Hasegawa M, Wilson G, Russell LD, Meistrich ML
Source: Radiat Res, 1997 Apr;147(4), p. 457-67.
PMID: 9092926
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