The role of ultraviolet radiation in melanomagenesis

Thaler, Anna‐Katharina von; Kamenisch, York; Berneburg, Mark

doi:10.1111/j.1600-0625.2009.01025.x

Cited by 83 publications

(75 citation statements)

References 128 publications

(141 reference statements)

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“…UVA mediated DNA damage has also been suggested to activate p53 less effectively than UVB, thus inducing less apoptosis and retaining mutagenic photoproducts in the exposed cells. 32 Theoretically this could explain why it would take less time for frequent, high-dose (sunbed-)UVA to induce a CM 31,41 or to ''prepare the way'' 39 for other CM inducing processes, compared to the time needed for CM development after predominantly sun exposure (UVAþa higher proportion of UVB). With our limited data on hand about the frequency, time and amount of solar/outdoor UVR exposure (not only for tanning purposes) this is difficult to evaluate and this is a limitation of this prospective study as our questionnaire was constructed long before it was evident how important it would be to be able to differentiate between types of UV exposure.…”

Section: Sunbeds and Sunlampsmentioning

confidence: 99%

“…The precise pathogenesis of CM is still unknown, but the carcinogenicity of UVB have been ascribed to direct DNA damage, while the probable carcinogenicity of UVA have been explained by damage to DNA by indirect effects (reactive oxygen species, photoreactions and photoproducts). 31,32 The possibly carcinogenic effect of UVR from sunbeds does most likely not differ from that of natural UVR exposure.…”

Section: Sunbeds and Sunlampsmentioning

confidence: 99%

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A prospective, population‐based study of 40,000 women regarding host factors, UV exposure and sunbed use in relation to risk and anatomic site of cutaneous melanoma

Nielsen

Måsbäck

Olsson

et al. 2011

Intl Journal of Cancer

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Prospective cohort studies about cutaneous melanoma (CM) risk are still few. Host factor-and UVR exposure data were collected prospectively by questionnaire in this population-based cohort study including 40,000 Swedish born women, aged 25-64 years at enrolment (1990). Risk for CM (Cox regression and Stepwise Cox regression [SCR], hazard ratios [HRs] with 95% Confidence Intervals [CI]) in relation to risk factors, age groups (older or younger than 40 years) and primary site, were analyzed. In 29,520 women with complete follow-up through 2007, 155 invasive and 60 in situ CM were recorded. High numbers of nevi (HR, 2.9; 95% CI, 1.7-5.0) and heredity (HR, 3.7; 95% CI, 2.0-6.8) were associated with risk for CM. SCR analysis added red hair as a risk factor. Sunbed use >10 times/year increased risk for women <40 years (HR, 2.5; 95% CI, 1.0-6.2) and a trend for risk associated with sunbathing vacations (HR, 1.4; 95% CI, 1.0-2.0) was shown for women >40 years. Trunk melanoma showed correlations with high numbers of nevi (HR, 3.0; 95% CI, 1.2-7.3) and heredity (HR, 3.2; 95% CI, 1.1-9.4). Head/neck site was correlated to sunbathing vacations (HR, 2.5; 95% CI, 1.2-5.3) and heredity (HR, 7.6; 95% CI, 1.8-31.8). Our study supports divergent etiologic pathways to CM, with high numbers of nevi correlated to increased risk for trunk CM. Furthermore, it confirms that high numbers of nevi, red hair and heredity for CM are the most important risk factors and frequent sunbed use might be a risk factor for younger women.The incidence of cutaneous melanoma (CM) has increased during the past decades among fair-skinned populations all around the world and is the most fatal form of skin cancer. 1In Sweden, CM represents a considerable growing public health burden, as the incidence has risen five times since the early sixties and the latest reported average annual incidence increase was 4.2% for women and 4.1% for men.2 The explanation to this rapid increase is not entirely understood but risk factors associated with CM are most certainly both related to the host (genetic and phenotypic factors), the environment [e.g., natural and artificial ultraviolet radiation (UVR) exposure] and interactions there between.

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Section: Sunbeds and Sunlampsmentioning

confidence: 99%

Section: Sunbeds and Sunlampsmentioning

confidence: 99%

A prospective, population‐based study of 40,000 women regarding host factors, UV exposure and sunbed use in relation to risk and anatomic site of cutaneous melanoma

Nielsen

Måsbäck

Olsson

et al. 2011

Intl Journal of Cancer

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“…4 Particular attention has been paid to the mechanisms responsible for DNA mutations which are of central importance for malignant transformation. UVB can directly induce DNA photoproducts such as cyclobutane pyrimidine dimers.…”

mentioning

confidence: 99%

Neonatal UVB exposure accelerates melanoma growth and enhances distant metastases in Hgf‐Cdk4^R24C C57BL/6 mice

Gaffal

Landsberg

Bald

et al. 2011

Intl Journal of Cancer

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Genetically engineered mouse models offer new opportunities to experimentally investigate the impact of UV on melanoma pathogenesis. Here we irradiated a cohort of newborn 15 Hgf-Cdk4 R24C mice on the pigmented C57BL/6 background with one erythemogenic dose of 6 kJ/m 2 UVB and compared the development of nevi and melanoma with a cohort of 30 untreated HgfCdk4 R24C mice. Neonatal UVB exposure decreased the latency and accelerated the growth of primary melanomas resulting in a significantly decreased time from melanoma onset to melanoma-related death (61 days vs. 96 days). Interestingly, we did not observe differences in the development of melanocytic nevi. Histopathological investigations revealed that UVB irradiation shifted the spectrum of melanomas toward a more aggressive phenotype with increased tumor cell proliferation, invasive growth and enhanced angiogenesis. Accordingly, we observed distal melanoma metastases in the lungs more frequently in the UV-irradiated than in the untreated cohort of Hgf-Cdk4 R24C mice (73% vs. 47%). UVB-induced melanomas only contained very few infiltrating immune cells and expressed very low levels of proinflammatory chemokines. Taken together, our results demonstrate that neonatal UVB exposure promoted the early appearance of rapidly enlarging primary melanomas in HgfCdk4 R24C C57BL/6 mice which showed enhanced invasive and metastatic behaviour without a persistent tumor-associated inflammatory response. The preferential impact of UVB irradiation on the progression of melanoma without an effect on the development of nevi supports the hypothesis that the molecular targets of UVB are involved in bypassing the proliferative arrest of transformed melanocytes without alerting a cellular immune response.Epidemiological studies demonstrate that individuals with fair skin and blond or red hair living in countries at low latitudes with high solar radiation levels have the highest incidence of malignant melanoma. 1 It has been proposed that intermittent intense UV exposure with sunburn during childhood precipitates the development of freckles and nevi because melanocytes with low melanin content and low basal DNA repair capacity are particularly susceptible to UV-induced mutations.2 This hypothesis would explain studies showing a direct correlation between sun exposure and the number of nevi in school children.3 A high nevus count and a family history of melanoma considerably increase the lifetime risk of developing a melanoma. Currently, the mechanisms by which UV radiation as an environmental carcinogen and host factors such as the individual genetic constitution contribute to melanomagenesis are incompletely understood.The biologic effects of UV radiation on cells in the skin have been studied in great detail in vitro and in vivo in mice and man. 4 Particular attention has been paid to the mechanisms responsible for DNA mutations which are of central importance for malignant transformation. UVB can directly induce DNA photoproducts such as cyclobutane pyrimidine dimers. In addition, b...

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“…BRAF-mutáció esetén sejtfelszíni receptor-aktiváció nélkül is aktív a MAPK-útvonal, ami számos tumorsejt-jellemzőt magyaráz. A BRAF-inhibitor a mutáns BRAF tirozin-kinázt gátolva csökkenti a MAPK-útvonal aktivitást, ezáltal akadályozza a tumornövekedést vetkezménye (10). Ez azonban nem zárja ki, hogy az UV-sugárzás közvetetten, más génmutációk révén vagy szignalizációs útvonalak befolyásolásával ne játszana szerepet BRAF mutáns melanoma kialakulásában, progressziójában (11).…”

Section: A Braf Mutáció Pathogenetikai Szerepe Melanomábanunclassified

Targeted therapy for BRAF-mutation positive metastatic melanoma

Szabó¹,

Ócsai²,

Kiss³

et al. 2017

BVSZ

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ÖSSZEFOGLALÁS A BRAFV600E/K génmutáció a melanoma kialakulásá-ban és progressziójában is fontos pathogenetikai tényező. Az esetek felében kimutatható a tumor metasztázisban és hatásának ellensúlyozására kifejlesztett célzott molekulá- Kulcsszavak: áttétes melanoma -BRAF inhibitor -MEK inhibitor -gyógyszer mellékhatás SUMMARY An important pathogenic factor in both the development and progression of melanoma is the V600E/K mutation of BRAF, which can be found in half of metastatic tumors. It is unsurprising therefore that molecular inhibitors targeting its effect are able to offer significantly higher progression free and overall survival as compared to conventional chemotherapy in the majority of patients diagnosed with metastatic melanoma. Moreover, the combination of BRAF-and MEK inhibitor therapy has greatly improved the prognosis of patients with confirmed mutations in distant metastases, showing that optimal use of new therapeutic agents by broadening clinical expertise is an effective way of expanding the inventory of anti-melanoma agents. The management of potential adverse events related to new treatments is also improved by their widespread use and the consequent enhancement of practical knowledge related to the new agents, ultimately leading to the improvement of quality of life of patients. Key words: metastatic melanoma -BRAF inhibitor -MEK inhibitor -drug adverse eventA melanoma pathofiziológiájáról szerzett, az elmúlt év-tizedben robbanásszerűen felhalmozódott ismereteink és a modern biotechnológia lehetővé tették új típusú onkoterá-piák megjelenését, mint amilyenek a célzott molekuláris inhibitorok vagy a biológiai terápiák, és ezzel megváltoztatták a metasztatikus betegek túlélési esélyeit és átírták a korábbi kezelési irányvonalakat (1-3). A melanoma kialakulásában és progressziójában kulcsszerepet játszó génmutációk komplex módon, az intracelluláris jelátviteli folyamatok kö-zötti egyensúly megbomlását okozva vezetnek megnöve-kedett sejttúléléséhez, kórosan fokozott sejtproliferációhoz. Az egyik legfontosabb pathogenetikai lépés a MAPK (Mitogén Aktivált Protein-Kináz)-útvonal aktivitásának fokozódása (4), ami igen gyakran, a melanomás eseteknek a 160 Levelező szerző: Dr. Szabó Imre Lőrinc

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The role of ultraviolet radiation in melanomagenesis

Cited by 83 publications

References 128 publications

A prospective, population‐based study of 40,000 women regarding host factors, UV exposure and sunbed use in relation to risk and anatomic site of cutaneous melanoma

A prospective, population‐based study of 40,000 women regarding host factors, UV exposure and sunbed use in relation to risk and anatomic site of cutaneous melanoma

Neonatal UVB exposure accelerates melanoma growth and enhances distant metastases in Hgf‐Cdk4^R24C C57BL/6 mice

Targeted therapy for BRAF-mutation positive metastatic melanoma

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The role of ultraviolet radiation in melanomagenesis

Cited by 83 publications

References 128 publications

A prospective, population‐based study of 40,000 women regarding host factors, UV exposure and sunbed use in relation to risk and anatomic site of cutaneous melanoma

A prospective, population‐based study of 40,000 women regarding host factors, UV exposure and sunbed use in relation to risk and anatomic site of cutaneous melanoma

Neonatal UVB exposure accelerates melanoma growth and enhances distant metastases in Hgf‐Cdk4R24C C57BL/6 mice

Targeted therapy for BRAF-mutation positive metastatic melanoma

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Resources

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Neonatal UVB exposure accelerates melanoma growth and enhances distant metastases in Hgf‐Cdk4^R24C C57BL/6 mice