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Sildenafil Use and Increased Risk of Incident Melanoma in US Men

Sildenafil Use and Increased Risk of Incident Melanoma in US Men ImportanceThe 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. ObjectiveTo evaluate the association between sildenafil use and risk of incident melanoma among men in the United States. Design, Setting, and ParticipantsOur 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 MeasuresThe 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. ResultsWe 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 RelevanceSildenafil 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Internal Medicine American Medical Association

Sildenafil Use and Increased Risk of Incident Melanoma in US Men

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Publisher
American Medical Association
Copyright
Copyright 2014 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.
ISSN
2168-6106
eISSN
2168-6114
DOI
10.1001/jamainternmed.2014.594
pmid
24710960
Publisher site
See Article on Publisher Site

Abstract

ImportanceThe 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. ObjectiveTo evaluate the association between sildenafil use and risk of incident melanoma among men in the United States. Design, Setting, and ParticipantsOur 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 MeasuresThe 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. ResultsWe 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 RelevanceSildenafil 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

JAMA Internal Medicine – American Medical Association

Published: Jun 1, 2014

References

  • Melanoma biology and new targeted therapy.
    Gray-Schopfer, V; Wellbrock, C; Marais, R
  • Cutaneous melanoma.
    Thompson, JF; Scolyer, RA; Kefford, RF
  • Cancer statistics, 2012.
    Siegel, R; Naishadham, D; Jemal, A
  • Detection of B-RAF and N-RAS mutations in human melanoma.
    Goydos, JS; Mann, B; Kim, HJ
  • Mutations of the BRAF gene in human cancer.
    Davies, H; Bignell, GR; Cox, C
  • Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial.
    Hauschild, A; Grob, JJ; Demidov, LV
  • Vemurafenib: the first drug approved for BRAF-mutant cancer.
    Bollag, G; Tsai, J; Zhang, J
  • Oncogenic BRAF induces melanoma cell invasion by downregulating the cGMP-specific phosphodiesterase PDE5A.
    Arozarena, I; Sanchez-Laorden, B; Packer, L
  • Identification of direct transcriptional targets of V600EBRAF/MEK signalling in melanoma.
    Packer, LM; East, P; Reis-Filho, JS; Marais, R
  • Oncogenic Braf induces melanocyte senescence and melanoma in mice.
    Dhomen, N; Reis-Filho, JS; da Rocha Dias, S
  • Hard times for oncogenic BRAF-expressing melanoma cells.
    Houslay, MD
  • An update on new oral PDE5 inhibitors for the treatment of erectile dysfunction.
    Palit, V; Eardley, I
  • Sildenafil: from angina to erectile dysfunction to pulmonary hypertension and beyond.
    Ghofrani, HA; Osterloh, IH; Grimminger, F
  • PDE5 inhibitor promotes melanin synthesis through the PKG pathway in B16 melanoma cells.
    Zhang, X; Yan, G; Ji, J
  • Melanoma induction by ultraviolet A but not ultraviolet B radiation requires melanin pigment.
    Noonan, FP; Zaidi, MR; Wolnicka-Glubisz, A
  • Melanoma and Viagra: an unexpected connection.
    Mitra, D; Robinson, KC; Fisher, DE
  • Non-melanoma skin cancer.
    Madan, V; Lear, JT; Szeimies, RM
  • Sexual function in men older than 50 years of age: results from the health professionals follow-up study.
    Bacon, CG; Mittleman, MA; Kawachi, I; Giovannucci, E; Glasser, DB; Rimm, EB
  • Restless legs syndrome and erectile dysfunction.
    Gao, X; Schwarzschild, MA; O’Reilly, EJ; Wang, H; Ascherio, A
  • Risk factors and individual probabilities of melanoma for whites.
    Cho, E; Rosner, BA; Feskanich, D; Colditz, GA
  • Risk factors for skin cancers: a nested case-control study within the Nurses’ Health Study.
    Han, J; Colditz, GA; Hunter, DJ
  • Host risk factors, ultraviolet index of residence, and incident malignant melanoma in situ among US women and men.
    Walls, AC; Han, J; Li, T; Qureshi, AA
  • Obesity and risk of malignant melanoma: a meta-analysis of cohort and case-control studies.
    Sergentanis, TN; Antoniadis, AG; Gogas, HJ
  • Smoking and risk of skin cancer: a prospective analysis and a meta-analysis.
    Song, F; Qureshi, AA; Gao, X; Li, T; Han, J
  • Validation of questionnaire information on risk factors and disease outcomes in a prospective cohort study of women.
    Colditz, GA; Martin, P; Stampfer, MJ
  • Diet and risk of basal cell carcinoma of the skin in a prospective cohort of women.
    Hunter, DJ; Colditz, GA; Stampfer, MJ; Rosner, B; Willett, WC; Speizer, FE
  • Inappropriate use of bivariable analysis to screen risk factors for use in multivariable analysis.
    Sun, GW; Shook, TL; Kay, GL
  • Are phosphodiesterase type 5 inhibitors associated with vision-threatening adverse events? a critical analysis and review of the literature.
    Azzouni, F; Abu samra, K
  • Sildenafil reverses cardiac dysfunction in the mdx mouse model of Duchenne muscular dystrophy.
    Adamo, CM; Dai, DF; Percival, JM
  • Sildenafil increases chemotherapeutic efficacy of doxorubicin in prostate cancer and ameliorates cardiac dysfunction.
    Das, A; Durrant, D; Mitchell, C
  • cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action.
    Francis, SH; Busch, JL; Corbin, JD; Sibley, D
  • Viagra deafness—sensorineural hearing loss and phosphodiesterase-5 inhibitors.
    Khan, AS; Sheikh, Z; Khan, S; Dwivedi, R; Benjamin, E
  • A Rac-cGMP signaling pathway.
    Guo, D; Tan, YC; Wang, D
  • Cell communication networks in cancer invasion.
    Calvo, F; Sahai, E
  • RAS oncogenes: the first 30 years.
    Malumbres, M; Barbacid, M
  • In vivo switching of human melanoma cells between proliferative and invasive states.
    Hoek, KS; Eichhoff, OM; Schlegel, NC
  • Melanoma.
    Miller, AJ; Mihm, MC
  • The association between MC1R genotype and BRAF mutation status in cutaneous melanoma: findings from an Australian population.
    Hacker, E; Hayward, NK; Dumenil, T; James, MR; Whiteman, DC

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