Person:

Gupta, Sameer

A female advantage in melanoma incidence and outcome has been consistently observed but remains unexplained. We hypothesized that tumors are genetically distinct between men and women and analyzed the mutation spectra in 266 metastatic melanomas (102 women and 164 men) from The Cancer Genome Atlas (TCGA). We found a statistically significantly greater burden of missense mutations among men (male median 298 vs female median = 211.5; male-to-female ratio [M:F] = 1.85, 95% confidence interval [CI] = 1.44 to 2.39). We validated these initial findings using available data from a separate melanoma exome cohort (n = 95) and found a similar increase in missense mutations among men (male median 393 vs female median 259; M:F = 1.59, 95% CI = 1.12 to 2.27). In addition, survival improves with increasing log-transformed missense mutation count (univariate hazard ratio = 0.82, 95% CI = 0.69 to 0.98) for TCGA samples. Our analyses are the first to demonstrate a gender difference in mutation burden in cutaneous melanoma.

Background: Gender disparity in melanoma outcome is consistently observed, suggesting that gender is as an important prognostic factor. However, the source of this gender disparity in melanoma remains unclear. Objective: This article reviews advances in our understanding of gender differences in melanoma and how such differences may contribute to outcomes. Methods: A broad literature search was conducted using the PubMed database, with search terms such as ‘gender differences in melanoma’ and ‘sex differences in melanoma.’ Additional articles were identified from cited references. Results: Herein, we address the gender-linked physiologic differences in skin and melanoma. We discuss the influence of estrogen on a woman’s risk for melanoma and melanoma outcomes with regard to pregnancy, oral contraceptives, hormone replacement therapy, and UV tanning. Conclusions: The published findings on gender disparities in melanoma have yielded many advances in our understanding of this disease. Biological, environmental, and behavioral factors may explain the observed gender difference in melanoma incidence and outcome. Further research will enable us to learn more about melanoma pathogenesis, with the goal of offering better treatments and preventative advice to our patients.