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

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.




Response to "Comments on sirolimus use and risk of cutaneous squamous cell carcinoma (SCC) in solid organ transplant recipients" (SOTRs).
Authors: Asgari M.M. , Arron S. , Warton E.M. , Quesenberry C.P. , Weisshaar D. .
Source: Journal Of The American Academy Of Dermatology, 2022 May; 86(5), p. e205-e206.
PMID: 35430053
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Genetic ancestry, skin pigmentation, and the risk of cutaneous squamous cell carcinoma in Hispanic/Latino and non-Hispanic white populations.
Authors: Jorgenson E. , Choquet H. , Yin J. , Hoffmann T.J. , Banda Y. , Kvale M.N. , Risch N. , Schaefer C. , Asgari M.M. .
Source: Communications Biology, 2020-12-14 00:00:00.0; 3(1), p. 765.
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Source: Proceedings Of The National Academy Of Sciences Of The United States Of America, 2020-07-14 00:00:00.0; 117(28), p. 16500-16508.
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Genetic and environmental factors underlying keratinocyte carcinoma risk.
Authors: Choquet H. , Ashrafzadeh S. , Kim Y. , Asgari M.M. , Jorgenson E. .
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Correlates of multiple cutaneous squamous cell carcinoma: A retrospective cohort study.
Authors: Kim Y. , Su K.A. , Asgari M.M. .
Source: Journal Of The American Academy Of Dermatology, 2020 02; 82(2), p. 497-499.
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Keratinocyte Carcinomas: Current Concepts and Future Research Priorities.
Authors: Nagarajan P. , Asgari M.M. , Green A.C. , Guhan S.M. , Arron S.T. , Proby C.M. , Rollison D.E. , Harwood C.A. , Toland A.E. .
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2019-04-15 00:00:00.0; 25(8), p. 2379-2391.
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A Prediction Tool to Facilitate Risk-Stratified Screening for Squamous Cell Skin Cancer.
Authors: Wang W. , Jorgenson E. , Ioannidis N.M. , Asgari M.M. , Whittemore A.S. .
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Photosensitizing antihypertensive drug use and risk of cutaneous squamous cell carcinoma.
Authors: Su K.A. , Habel L.A. , Achacoso N.S. , Friedman G.D. , Asgari M.M. .
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Gene expression imputation identifies candidate genes and susceptibility loci associated with cutaneous squamous cell carcinoma.
Authors: Ioannidis N.M. , Wang W. , Furlotte N.A. , Hinds D.A. , 23andMe Research Team , Bustamante C.D. , Jorgenson E. , Asgari M.M. , Whittemore A.S. .
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Genetic variants in the HLA class II region associated with risk of cutaneous squamous cell carcinoma.
Authors: Wang W. , Ollila H.M. , Whittemore A.S. , Demehri S. , Ioannidis N.M. , Jorgenson E. , Mignot E. , Asgari M.M. .
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Common mitochondrial haplogroups and cutaneous squamous cell carcinoma risk.
Authors: Jorgenson E. , Choquet H. , Yin J. , Asgari M.M. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2018-04-25 00:00:00.0; , .
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Susceptibility Loci-Associated Cutaneous Squamous Cell Carcinoma Invasiveness.
Authors: Wang W. , Jorgenson E. , Whittemore A.S. , Asgari M.M. .
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Quantifying the Polygenic Contribution to Cutaneous Squamous Cell Carcinoma Risk.
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Research gaps in the management and prevention of cutaneous squamous cell carcinoma in organ transplant recipients.
Authors: Blomberg M. , He S.Y. , Harwood C. , Arron S.T. , Demehri S. , Green A. , Asgari M.M. , NCI Keratinocyte Carcinoma Consortium .
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Towards the use of precision medicine in predicting cutaneous squamous cell carcinoma risk among solid organ transplant recipients.
Authors: Nguyen M.O. , Nguyen H.T. , Asgari M.M. .
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Research Techniques Made Simple: An Introduction to Use and Analysis of Big Data in Dermatology.
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Cutaneous Squamous Cell Cancer (cscc) Risk And The Human Leukocyte Antigen (hla) System
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IRF4 Polymorphism Is Associated with Cutaneous Squamous Cell Carcinoma in Organ Transplant Recipients: A Pigment-Independent Phenomenon.
Authors: Asgari M.M. , Toland A.E. , Arron S.T. .
Source: The Journal Of Investigative Dermatology, 2017 Jan; 137(1), p. 251-253.
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Population Variations in Rheumatoid Arthritis Treatment and Outcomes, Northern California, 1998-2009.
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Geographic Clusters of Basal Cell Carcinoma in a Northern California Health Plan Population.
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A Gwas Of Cutaneous Squamous Cell Carcinoma-letter
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Family history of skin cancer is associated with increased risk of cutaneous squamous cell carcinoma.
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