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Sildenafil use and increased risk of incident melanoma in US men: a prospective cohort study.

Abstract：

IMPORTANCE:The RAS/RAF/mitogen-activated protein kinase and extracellular signal-regulated kinase (ERK) kinase/ERK cascade plays a crucial role in melanoma cell proliferation and survival. Sildenafil citrate (Viagra) is a phosphodiesterase (PDE) 5A inhibitor commonly used for erectile dysfunction. Recent studies have shown that BRAF activation down-regulates PDE5A levels, and low PDE5A expression by BRAF activation or sildenafil use increases the invasiveness of melanoma cells, which raises the possible adverse effect of sildenafil use on melanoma risk. OBJECTIVE:To evaluate the association between sildenafil use and risk of incident melanoma among men in the United States. DESIGN, SETTING, AND PARTICIPANTS:Our study is a prospective cohort study. In 2000, participants in the Health Professionals' Follow-up Study were questioned regarding sildenafil use for erectile dysfunction. Participants who reported cancers at baseline were excluded. A total of 25,848 men remained in the analysis. MAIN OUTCOMES AND MEASURES:The incidence of skin cancers, including melanoma, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC), was obtained in the self-reported questionnaires biennially. The diagnosis of melanoma and SCC was pathologically confirmed. RESULTS:We identified 142 melanoma, 580 SCC, and 3030 BCC cases during follow-up (2000-2010). Recent sildenafil use at baseline was significantly associated with an increased risk of subsequent melanoma with a multivariate-adjusted hazard ratio (HR) of 1.84 (95% CI, 1.04-3.22). In contrast, we did not observe an increase in risk of SCC (HR, 0.84; 95% CI, 0.59-1.20) or BCC (1.08; 0.93-1.25) associated with sildenafil use. Moreover, erectile function itself was not associated with an altered risk of melanoma. Ever use of sildenafil was also associated with a higher risk of melanoma (HR, 1.92; 95% CI, 1.14-3.22). A secondary analysis excluding those reporting major chronic diseases at baseline did not appreciably change the findings; the HR of melanoma was 2.24 (95% CI, 1.05-4.78) for sildenafil use at baseline and 2.77 (1.32-5.85) for ever use. CONCLUSIONS AND RELEVANCE:Sildenafil use may be associated with an increased risk of developing melanoma. Although this study is insufficient to alter clinical recommendations, we support a need for continued investigation of this association.

journal_name

JAMA Intern Med

journal_title

JAMA internal medicine

authors

Li WQ,Qureshi AA,Robinson KC,Han J

doi

10.1001/jamainternmed.2014.594

subject

Has Abstract

pub_date

2014-06-01 00:00:00

pages

964-70

issue

eissn

2168-6106

issn

2168-6114

pii

1857095

journal_volume

174

pub_type

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Sildenafil use and increased risk of incident melanoma in US men: a prospective cohort study.