For Residents
Molecular Mechanisms of Melanoma
There has been a rapid accumulation of knowledge regarding the altered molecular pathways in melanoma. With the development of target therapies...
A recently published prospective cohort study reported that sildenafil use may increase the risk for melanoma (JAMA Intern Med. 2014;174:964-970). BRAF activation, which is pathogenic in some melanoma variants, downregulates phosphodiesterase 5A and sildenafil downregulates phosphodiesterase 5A, surmising that either one may enhance melanoma invasion. The Health Professionals’ Follow-up Study cohort was utilized, which has prospectively evaluated male health professionals’ nutrition and incidences of serious illnesses since 1986. In 2000, more than 25,000 men were interviewed about sildenafil use for erectile dysfunction, and the incidence of skin cancer was obtained by questionnaire every 2 years for 10 years. The questionnaire showed that 142 melanomas were diagnosed, and recent or prior sildenafil use (with no breakdown of frequency of dosing) was significantly associated with increased risk for melanoma (hazard ratio, 1.84 for recent use; 1.92 for ever use) adjusted for age, erectile dysfunction without sildenafil, and several skin-related and genetic melanoma risk factors. No other types of skin cancer exhibited this risk trend.
What’s the issue?
Vascular tone and manipulation of such is a contender as a hot topic in melanoma given that even aspirin has been implicated as a risk factor. Unfortunately, similar to the aspirin data, without a true continuum providing any sildenafil dosage or frequency relationship to the development of melanoma, especially for this very short half-life medication, we likely cannot consider sildenafil as a hazard in patients at high risk for melanoma as we do for smokers and oral contraceptives, or alcoholics and terbinafine. Because UV radiation is the only behavioral risk factor linked to melanoma and considering that so many of our male patients take this class of drug, in your opinion what percentage of your patients in this risk category follow strict sun protection? Should we mention this potential association to them?
