Basal cell carcinoma (BCC) is the most common malignancy in the United States;however, it has been relatively understudied in epidemiologic research. Temporal trends indicate that BCC incidence is increasing overall, in young adults, and especially in young women. Data from """"""""early onset"""""""" cases support the concept that there are at least two different subgroups accounting for BCCs in individuals below the age of 40?a group with single tumors whose incidence is increasing, presumably due to environmental factors, and a group with multiple tumors whose incidence is stable and who probably have hereditary predisposition to BCCs. The purpose of this study is to assess genetic and environmental risk factors for early onset BCCs and explore the interaction between these factors. This study is an outgrowth of our previous work showing that the PTCH gene underlies both hereditary and sporadic BCCs but applies and extends this work at a population level, with careful consideration of environmental contributions to the disease incidence. Five hundred cases with early onset BCC and 500 controls with benign skin conditions will be recruited from the Yale dermatopathology database for interviews and collection of biological samples. Questionnaire data will be used to assess potential environmental factors that might be related to the increased incidence, especially artificial tanning, excessive solar radiation exposure, smoking, and obesity. The interaction between these environmental variables and genetic variants of MC1R, known to relate to skin cancer susceptibility, will be assessed. Tumors from selected subjects in whom BCC risk appears to be related strongly to a particular environmental exposure will undergo sequencing of the PTCH gene to relate the reported exposure to """"""""signature mutations"""""""" in DNA. Subjects with large numbers of BCCs or particularly early age of onset of BCCs will have detailed genetic studies to determine if they have a known hereditary disorder, and if not, to identify novel BCC predisposition genes. Risk factor data are needed to serve as a basis to guide preventive interventions. For example, strong evidence that tanning bed use is an important etiologic factor in early onset BCC, with supporting evidence showing mutational spectra consistent with UVB mutations, could form the basis for stronger legislation to prevent tanning bed use by minors. Alternatively, if smoking or other risk factors are more strongly associated, this suggests a different intervention strategy to reduce the disease. Identification of underlying predisposition genes may help target efforts at prevention to particular genetic subgroups. Thus, this etiologic work is highly and immediately translatable into preventive interventions aimed at reducing the incidence of this exceedingly common malignancy.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Yale University
New Haven
United States
Zip Code
Krauthammer, Michael (2018) Unraveling the etiology of primary malignant melanoma of the esophagus. J Thorac Dis 10:S1074-S1075
Das, Rituparna; Bar, Noffar; Ferreira, Michelle et al. (2018) Early B cell changes predict autoimmunity following combination immune checkpoint blockade. J Clin Invest 128:715-720
Ferrucci, Leah M; Cartmel, Brenda; Clare, Rachel A et al. (2018) Cross-sectional assessment of ultraviolet radiation-related behaviors among young people after a diagnosis of melanoma or basal cell carcinoma. J Am Acad Dermatol 79:149-152
Arbesman, Joshua; Ravichandran, Sairekha; Funchain, Pauline et al. (2018) Melanoma cases demonstrate increased carrier frequency of phenylketonuria/hyperphenylalanemia mutations. Pigment Cell Melanoma Res 31:529-533
Perry, Curtis J; Muñoz-Rojas, Andrés R; Meeth, Katrina M et al. (2018) Myeloid-targeted immunotherapies act in synergy to induce inflammation and antitumor immunity. J Exp Med 215:877-893
Liu, Xiaoni; Zhang, Shang-Min; McGeary, Meaghan K et al. (2018) KDM5B Promotes Drug Resistance by Regulating Melanoma Propagating Cell Subpopulations. Mol Cancer Ther :
Sulkowski, Parker L; Scanlon, Susan E; Oeck, Sebastian et al. (2018) PTEN Regulates Nonhomologous End Joining By Epigenetic Induction of NHEJ1/XLF. Mol Cancer Res 16:1241-1254
Chen, Ling; Azuma, Takeshi; Yu, Weiwei et al. (2018) B7-H1 maintains the polyclonal T cell response by protecting dendritic cells from cytotoxic T lymphocyte destruction. Proc Natl Acad Sci U S A 115:3126-3131
Miller, Chad J; Muftuoglu, Yagmur; Turk, Benjamin E (2017) A high throughput assay to identify substrate-selective inhibitors of the ERK protein kinases. Biochem Pharmacol 142:39-45
Kluger, Harriet M; Zito, Christopher R; Turcu, Gabriela et al. (2017) PD-L1 Studies Across Tumor Types, Its Differential Expression and Predictive Value in Patients Treated with Immune Checkpoint Inhibitors. Clin Cancer Res 23:4270-4279

Showing the most recent 10 out of 172 publications