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.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Project (R01)
Project #
Application #
Study Section
Arthritis, Connective Tissue and Skin Study Section (ACTS)
Program Officer
Carrick, Danielle M
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Kaiser Foundation Research Institute
United States
Zip Code
Wang, Wei; Ollila, Hanna M; Whittemore, Alice S et al. (2018) Genetic variants in the HLA class II region associated with risk of cutaneous squamous cell carcinoma. Cancer Immunol Immunother :
Sordillo, Joanne E; Kraft, Peter; Wu, Ann Chen et al. (2018) Quantifying the Polygenic Contribution to Cutaneous Squamous Cell Carcinoma Risk. J Invest Dermatol 138:1507-1510
Ioannidis, Nilah M; Wang, Wei; Furlotte, Nicholas A et al. (2018) Gene expression imputation identifies candidate genes and susceptibility loci associated with cutaneous squamous cell carcinoma. Nat Commun 9:4264
Wang, Wei; Jorgenson, Eric; Whittemore, Alice S et al. (2018) Susceptibility Loci-Associated Cutaneous Squamous Cell Carcinoma Invasiveness. J Invest Dermatol 138:557-561
Jorgenson, Eric; Choquet, Hélène; Yin, Jie et al. (2018) Common Mitochondrial Haplogroups and Cutaneous Squamous Cell Carcinoma Risk. Cancer Epidemiol Biomarkers Prev 27:838-841
Su, K A; Habel, L A; Achacoso, N S et al. (2018) Photosensitizing antihypertensive drug use and risk of cutaneous squamous cell carcinoma. Br J Dermatol 179:1088-1094
Wehner, Mackenzie R; Levandoski, Katherine A; Kulldorff, Martin et al. (2017) Research Techniques Made Simple: An Introduction to Use and Analysis of Big Data in Dermatology. J Invest Dermatol 137:e153-e158
Nguyen, M O; Nguyen, H T; Asgari, M M (2017) Towards the use of precision medicine in predicting cutaneous squamous cell carcinoma risk among solid organ transplant recipients. Br J Dermatol 177:901-902
Yesantharao, Pooja; Wang, Wei; Ioannidis, Nilah M et al. (2017) Cutaneous squamous cell cancer (cSCC) risk and the human leukocyte antigen (HLA) system. Hum Immunol 78:327-335
Blomberg, M; He, S Y; Harwood, C et al. (2017) Research gaps in the management and prevention of cutaneous squamous cell carcinoma in organ transplant recipients. Br J Dermatol 177:1225-1233

Showing the most recent 10 out of 27 publications