Age-dependent sex disparity in cutaneous melanoma: A possible role of androgen receptor

Summary: Abstract Body: Comparing to women, men are more susceptible to cancer in general, including higher incidence rates and higher mortality rates. For cutaneous melanoma (CM), this discrepancy is dependent on age. Younger women and older men are more susceptible to CM. The mechanism is not fully understood. Using both epidemiological and molecular biology approaches, we discovered an important role of androgen receptor in CM development and cell proliferation, coordinate with testosterone levels and estrogen levels. Testosterone, in contrast to a general perception, in fact is protective against CM development. This is coordinated with our finding that increased testosterone levels in cell culture can speed up DNA damage repair (8-OxoG and PARP1 as markers). However, once the tumor is initiated, testosterone and AR can stimulate melanoma cell proliferation and even confer drug resistance. Using AR over-expression and an AR-degrading agent we have developed, we demonstrated these roles in vitro in melanoma cells. If these results are further validated at molecular levels in vivo and at population levels in human cohorts, we can develop specific preventive screening methods and new therapeutic modality. Jianjian Lin¹, Ramesh Narayanan³, Feng Liu-Smith^{1, 2} 1. Preventive Medicine, The University of Tennessee Health Science Center College of Medicine, Memphis, TN, United States. 2. Department of Dermatology, The University of Tennessee Health Science Center College of Medicine, Memphis, TN, United States. 3. Medicine, The University of Tennessee Health Science Center College of Medicine, Memphis, TN, United States. Clinical Research: Epidemiology and Observational Research