This is an application for a K23 award for Dr. Jean Tang, a dermatologist at the University of California, San Francisco. Dr. Tang is establishing herself as a young investigator in patient-oriented, translational research in the prevention of basal cell carcinoma (BCC). This K23 award will provide Dr. Tang with the support necessary to accomplish the following goals: (1) to conduct a mouse preclinical trial on vitamin D for BCC prevention;(2) to conduct secondary data analysis in a large prospective cohort of senior men that have baseline vitamin D measurements;(3) to conduct a pilot clinical trial in humans to test the feasibility of topical or oral vitamin D3. To achieve these goals, Dr. Tang has assembled a mentoring team comprised of a primary mentor, Dr. Ervin Epstein, Scientist at Children's Hospital of Oakland Research Institute, who conducts laboratory and clinical trials in chemoprevention of BCC, and three co-mentors: Dr. Steven Cummings, Director of the San Francisco Coordinating Center who is an expert in clinical studies and trials of large patient cohorts;Dr. Mary-Margaret Chren, an expert in dermatology outcomes research;and Dr. Charles McCullough, who has expertise in longitudinal data analysis and biostatistics. Currently, there is no effective agent to prevent basal cell carcinomas (BCC). Sunscreens have not been shown to prevent BCC;however, recent in vitro data suggests that vitamin D3 inhibits the aberrant signaling pathway found in BCC. Dr. Tang has shown that topical application of vitamin D3 in mice will prevent 50% of BCCs. In this K23, she proposes to determine the optimal route of delivery of vitamin D3 for inhibition of BCC in mice (Aim 1) and to determine whether high levels of serum vitamin D reduce BCC risk in senior men (Aim 2). Dr. Tang will also conduct a pilot clinical trial to test the feasibility of topical and oral vitamin D3 in patients with basal cell nevus syndrome who have multiple BCCs (Aim 3). From the mouse preclinical trial and the human pilot trial, we will determine the optimal administration of vitamin D3 for inhibition of a biomarker of BCC. These results will provide critical preliminary data for a randomized controlled clinical trial using vitamin D3 for prevention of BCC tumors in Basal Cell Nevus Syndrome patients, which will be developed during the K award and submitted as a R34 grant application to the NIH at the end of Year 5.

Public Health Relevance

Sunscreens do not prevent basal cell carcinomas of the skin, the most common cancer found in the US. Our goal is to determine whether vitamin D is an effective and safe agent to prevent basal cell carcinomas.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23AR056736-04
Application #
8287193
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Baker, Carl
Project Start
2009-07-08
Project End
2013-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2012
Total Cost
$124,200
Indirect Cost
$9,200
Name
Stanford University
Department
Dermatology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Ally, Mina S; Tang, Jean Y; Joseph, Timmy et al. (2014) The use of vismodegib to shrink keratocystic odontogenic tumors in patients with basal cell nevus syndrome. JAMA Dermatol 150:542-5
Tang, Jean Y; Henderson, Michael T; Hernandez-Boussard, Tina et al. (2013) Lower skin cancer risk in women with higher body mass index: the women's health initiative observational study. Cancer Epidemiol Biomarkers Prev 22:2412-5
Gamba, Christina A; Swetter, Susan M; Stefanick, Marcia L et al. (2013) Aspirin is associated with lower melanoma risk among postmenopausal Caucasian women: the Women's Health Initiative. Cancer 119:1562-9
Gamba, Christina S; Stefanick, Marcia L; Shikany, James M et al. (2013) Low-fat diet and skin cancer risk: the women's health initiative randomized controlled dietary modification trial. Cancer Epidemiol Biomarkers Prev 22:1509-19
Spaunhurst, K M; Hogendorf, A M; Smith, F J D et al. (2012) Pachyonychia congenita patients with mutations in KRT6A have more extensive disease compared with patients who have mutations in KRT16. Br J Dermatol 166:875-8
Linos, Eleni; Keiser, Elizabeth; Kanzler, Matthew et al. (2012) Sun protective behaviors and vitamin D levels in the US population: NHANES 2003-2006. Cancer Causes Control 23:133-40
Keiser, Elizabeth; Linos, Eleni; Kanzler, Matthew et al. (2012) Reliability and prevalence of digital image skin types in the United States: results from National Health and Nutrition Examination Survey 2003-2004. J Am Acad Dermatol 66:163-5
Tang, Jean Y; Fu, Teresa; Leblanc, Erin et al. (2011) Calcium plus vitamin D supplementation and the risk of nonmelanoma and melanoma skin cancer: post hoc analyses of the women's health initiative randomized controlled trial. J Clin Oncol 29:3078-84
Tang, Jean Y; Xiao, Tony Zheng; Oda, Yuko et al. (2011) Vitamin D3 inhibits hedgehog signaling and proliferation in murine Basal cell carcinomas. Cancer Prev Res (Phila) 4:744-51
Tang, Tracy; Tang, Jean Y; Li, Dongwei et al. (2011) Targeting superficial or nodular Basal cell carcinoma with topically formulated small molecule inhibitor of smoothened. Clin Cancer Res 17:3378-87

Showing the most recent 10 out of 13 publications