Polymorphisms of Estrogen Receptors: Risk Factors for Invasive Melanoma – A Prospective Study

Giorgi, Vincenzo De; Sestini, Serena; Gori, Alessia; Mazzotta, Celestina; Grazzini, Marta; Rossari, Susanna; Mavilia, Carmelo; Crocetti, Emanuele; Brandi, Maria Luisa; Lotti, Torello; Massi, Daniela

doi:10.1159/000328321

Cited by 12 publications

(12 citation statements)

References 39 publications

(47 reference statements)

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“…Genetic mechanisms have also been implicated, although the available data are still inconclusive. A genetic link between obesity and pigmentation has been proposed, as well as the role of obesity susceptibility loci in determining the risk and aggressiveness of melanoma, involving, for instance, certain vitamin D receptor polymorphisms and genetic variations in IGF-1 or estrogen receptor pathways [5,45,48,49]. A strong association between Breslow index and the IGF-1(CA) 19 repeat frequency was found (P < 0.001) in one study [50].…”

Section: Discussionmentioning

confidence: 96%

Body Mass Index and Melanoma Prognosis

Cassano¹,

Caccavale

Veña³

et al. 2021

Dermatol Pract Concept

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Introduction: Obesity has been suggested as a risk factor in the progression of malignancies, including melanoma. Most studies defined obesity using body mass index (BMI), although the index is considered an imperfect measure of body composition. Objective: The aim of this article is to examine whether BMI can impact the prognosis of cutaneous melanoma, regardless of anti-tumor therapy. The relationship between BMI and specific prognostic factors in melanoma patients has been reviewed. Methods: Literature search was conducted on PubMed using the terms “melanoma” and “body mass index” or “obesity”. We selected articles, published up to 30 November 2020, examining the prognostic aspects of melanoma. Articles evaluating the risk and incidence of melanoma were excluded as well as studies regarding morbidity and complications following surgical procedures, or those performed in metastatic melanoma patients treated with anti-tumor therapies. Results: Mixed results have emerged from studies assessing the clinical outcomes in melanoma patients in relation to BMI. More consistent data seem to support the relationship between BMI and Breslow thickness. Conclusions: Studies that focus specifically on the link between obesity and melanoma prognosis are limited; further research is needed to deepen our knowledge on this link.

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Section: Discussionmentioning

confidence: 96%

Body Mass Index and Melanoma Prognosis

Cassano¹,

Caccavale

Veña³

et al. 2021

Dermatol Pract Concept

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“…ERβ expression has been recently shown to be downregulated in aggressive, metastatic melanomas, suggesting its possible utility as a marker for metastatic potential and for prognosis in malignant melanomas (108). Finally, a polymorphism at the Alu I restriction site was identified in a high proportion of melanoma, suggesting that the polymorphism of this receptor could be related to a higher susceptibility to the development of this tumor (109). …”

Section: Estrogen Receptor β and Melanomamentioning

confidence: 99%

Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility

et al. 2016

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Cutaneous melanoma is an aggressive tumor; its incidence has been reported to increase fast in the past decades. Melanoma is a heterogeneous tumor, with most patients harboring mutations in the BRAF or NRAS oncogenes, leading to the overactivation of the MAPK/ERK and PI3K/Akt pathways. The current therapeutic approaches are based on therapies targeting mutated BRAF and the downstream pathway, and on monoclonal antibodies against the immune checkpoint blockade. However, treatment resistance and side effects are common events of these therapeutic strategies. Increasing evidence supports that melanoma is a hormone-related cancer. Melanoma incidence is higher in males than in females, and females have a significant survival advantage over men. Estrogens exert their effects through estrogen receptors (ERα and ERβ) that affect cancer growth in an opposite way: ERα is associated with a proliferative action and ERβ with an anticancer effect. ERβ is the predominant ER in melanoma, and its expression decreases in melanoma progression, supporting its role as a tumor suppressor. Thus, ERβ is now considered as an effective molecular target for melanoma treatment. 17β-estradiol was reported to inhibit melanoma cells proliferation; however, clinical trials did not provide the expected survival benefits. In vitro studies demonstrate that ERβ ligands inhibit the proliferation of melanoma cells harboring the NRAS (but not the BRAF) mutation, suggesting that ERβ activation might impair melanoma development through the inhibition of the PI3K/Akt pathway. These data suggest that ERβ agonists might be considered as an effective treatment strategy, in combination with MAPK inhibitors, for NRAS mutant melanomas. In an era of personalized medicine, pretreatment evaluation of the expression of ER isoforms together with the concurrent oncogenic mutations should be considered before selecting the most appropriate therapeutic intervention. Natural compounds that specifically bind to ERβ have been identified. These phytoestrogens decrease the proliferation of melanoma cells. Importantly, these effects are unrelated to the oncogenic mutations of melanomas, suggesting that, in addition to their ERβ activating function, these compounds might impair melanoma development through additional mechanisms. A better identification of the role of ERβ in melanoma development will help increase the therapeutic options for this aggressive pathology.

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“…When restricting to those with malignant melanomas only, the OR was still increased, although it was not statistically significant. An association between oestrogen treatment and melanomas might be explained, as previously suggested, by a mechanism involving the oestrogen receptor-β in melanocytes [5]. With the lower doses of oestrogen used for oral contraception or postmenopausal hormone replacement therapy, no association between oestrogens and melanoma was found [6,7].…”

Section: Discussionmentioning

confidence: 99%

“…In a large meta-analysis of previous users of COCs, an increased risk of cervical cancer was found [4]. Although a role for oestrogen receptor-β in the development of malignant melanoma has been reported [5], so far no clear association between COC use and melanoma has been established [6,7]. It is important to increase our knowledge about possible long-term risks involved when young adolescent girls are considered for oestrogen treatment.…”

Section: Introductionmentioning

confidence: 99%

Risks of Malignant and Non-Malignant Tumours in Tall Women Treated with High-Dose Oestrogen during Adolescence

et al. 2014

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Background/Aim: High-dose oestrogen treatment has been used to reduce growth in tall adolescent girls. The long-term safety with regard to cancer has not been clarified. Our aim was to study if this growth reduction therapy affects cancer risk later in life. Methods: A cohort study of 369 (172 treated, 197 untreated) Swedish women who in 1973-1993 were assessed for tall adolescent stature was designed. Data were collected from university hospital records, patient questionnaires, and the Swedish Cancer Register. Results: Risks are presented as odds ratios (ORs) with 95% confidence intervals comparing treated to untreated subjects. In treated subjects, the overall OR for having a tumour (malignant or non-malignant) was 1.7 (0.8-3.8). The ORs were 2.3 (0.4-12.8) for breast tumours, 0.8 (0.2-2.6) for gynaecological tumours, and 6.1 (1.04-∞) for melanoma. When limiting to malignant tumours, the crude ORs were of similar magnitude. Conclusion: The OR for any melanoma was higher in treated than in untreated women, suggesting an increased risk of melanoma associated with high-dose oestrogen treatment during adolescence. Although the risk estimates were increased for overall tumours, breast tumours, malignant gynaecological tumours, and malignant melanoma, these associations were not statistically significant. Our results need to be verified in a larger cohort.

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Polymorphisms of Estrogen Receptors: Risk Factors for Invasive Melanoma – A Prospective Study

Cited by 12 publications

References 39 publications

Body Mass Index and Melanoma Prognosis

Body Mass Index and Melanoma Prognosis

Estrogen Receptor β in Melanoma: From Molecular Insights to Potential Clinical Utility

Risks of Malignant and Non-Malignant Tumours in Tall Women Treated with High-Dose Oestrogen during Adolescence

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