Molecular and Epigenetic Mechanisms of Gender Disparities in Early Onset Melanoma
|Feng Liu, Ph.D.
|Archana McEligot, Ph.D.
This project focuses on and extends our recent epidemiologic studies on a gender differences in early
onset cutaneous melanoma (CM). Our published results suggest that early onset melanoma may not be
directly caused by UV radiation alone, rather, gender-related issues play a more important role. To further
understand the mechanism of this phenomena, we propose a pathway mediated by estrogen and IGF1 that
leads to melanocytes proliferation and perhaps transformation. This hypothesis is based on our novel
molecular signal transduction results. To test this hypothesis, we propose to combine the skills and
experience from both PIs and analyze the problem from both molecular signal transduction and
epigenetic/population-based studies. First, the signal transduction pathway will be compared in male and
female melanocytes; Nox1, reactive oxygen species (ROS), cell proliferation, oxidative DNA damage will be
measured as outcome for estrogen and IGF1 impact (Aim 1). Secondly, the role of functional SNPs related
to estrogen receptors, IGF1, IGF1R, as well as CM risk factors will be explored and compared in a casecontrol
study (Gene, Environment and Melanoma study) in which DNA samples are available (Aim 2).
Furthermore, we plan to involve students with diverse ethnic background in this study to prepare a diverse
work force in cancer prevention. If the results of these specific aims confirm our initial observations and our
hypothesis, we will expand these studies to larger data sets in a future RO-1 application. Such results would
confirm a gender difference in early onset CM and may affect prevention approaches in this population.
To our knowledge, this is the first study attempting to decipher sex/gender differences at the molecular level
in CM etiology. This study should bring extensive epidemiological and molecular understanding of
differences in melanoma susceptibility between young men and women. Etiological factors in addition to sun
exposure will be examined. Hence, new avenues for hormone and/or gender related prevention strategies in
adolescence and young adult groups may evolve and contribute to melanoma prevention.