Cancer Risk: Why Do Women with Melanoma Do Better Than Men?

Source: eLife, January 2018

Melanoma is a deadly form of skin cancer that develops from pigment-producing cells called melanocytes. Men have a higher risk of developing this cancer than women, and a worse prognosis if they do. It has been suggested that social issues underlie this gender difference because, historically, men tended to work outdoors more than women, and thus received more exposure to the sun (which is the major risk factor for melanoma). Men are also less likely to visit a doctor and get suspicious-looking skin lesions examined. However, even when these and other similar factors are accounted for, men with melanoma still have poorer outcomes than their female counterparts (Joosse et al., 2013) – meaning something else must be happening as well.

It has long been suspected that female sex hormones are linked to the control of skin pigmentation. Indeed, observers as far back as Hippocrates noted that pregnancy was often associated with changes in skin coloration. Now, in eLife, Todd Ridky and colleagues from the University of Pennsylvania – including Christopher Natale as first author – report how the female sex hormone estrogen affects melanoma development and response to therapy (Natale et al., 2018).

Natale et al. started by growing a skin-like tissue that contained human melanocytes with a form of the cancer-causing oncogene BRAF that could be induced by a chemical called doxycycline (Wellbrock et al., 2004). This humanized skin was grafted onto the backs of mice that were then separated into two groups. One group was allowed to breed and the other was not. The mice were then fed doxycycline in their drinking water to activate the BRAF oncogene. After a period of 15 weeks, and three consecutive pregnancies in the breeding group, the humanized skin was collected from the mice and analyzed. In the non-breeding mice, the skin contained melanomas, but the skin from the pregnant mice did not and looked mostly normal.