Reactive oxygen species and melanoma: an explanation for gender differences in survival?

Summary Epidemiological research consistently shows a female advantage in melanoma survival. So far, no definite candidate for the explanation of this phenomenon has emerged. We propose that gender differences in oxidative stress caused by radical oxygen species (ROS) underlie these survival differences. It is known that males express lower amounts of anti‐oxidant enzymes, resulting in more oxidative stress than females. The primary melanoma environment is characterized by high ROS levels, from exogenous sources as well as ROS production within melanoma cells themselves. ROS are known to be able to promote metastasis through a wide variety of mechanisms. We hypothesize that the higher levels of ROS in men enhance selection of ROS‐resistance in melanoma cells. Subsequently, ROS can stimulate the metastatic potential of melanoma cells. In addition, due to the lower anti‐oxidant defenses in men, ROS produced by melanoma cells cause more damage to healthy tissues surrounding the tumor, further stimulating metastasis. Therefore, ROS may explain the observed differences between males and females in melanoma survival.