Divergent cancer pathways for early onset and late onset cutaneous malignant melanoma

Abstract

The interesting paper by Anderson et al 1 provides new data about the existence of age-related differing cancer pathways for melanoma, showing that sex, anatomic site, and histopathology are age-dependent effect modifiers of melanoma risk; however, it should consider sex-site interactions.Sex-specific risk patterns of melanoma by site are rarely studied, probably because of the amount of cases required and the assumption that differences in melanoma between sexes are not biologically relevant. We recently reported the striking sex differences observed in age distribution of trunk cutaneous melanoma in Sweden; incidence rates displayed a steady increase with age in men, but plateaued in women from perimenopausal ages.2 This pattern, only found in trunk ( Fig. 1), which could not be explained by cohort effect, has also been described in other countries.The curious age distribution in truncal melanoma in women is reminiscent of age changes in female breast cancer rates around menopause, and points toward a possible modulator role of sex hormones, specifically in female trunk melanoma. The role of hormones in melanoma is not well understood, although melanocytic cells are known to express estrogen receptors.3 Melanoma arising in sunsheltered areas such as trunk present frequent mutations in BRAF, which have been reported to be strongly associated with MC1R polymorphisms. The expression of this gene is modulated by endocrine sex hormones, 4 and has different functional effects by sex, as its variants modulate femalespecific mechanisms of analgesia. 5Melanoma at this site has stronger associations with pre-existing nevus and number of moles, perhaps a surrogate of inherited susceptibility. However, its most noteworthy distinctive epidemiological characteristic is the different proportion of cases in this location between sexes, which mimics nevus distribution observed in children, although the mechanisms underlying the site distribution of this tumor by sex are still unknown. These peculiarities make plausible that melanocyte regulation in trunk might have hormone-related specific features.

A new understanding in the epidemiology of melanoma

“…Interestingly, melanomas on the trunk of the body present frequent mutations in BRAF, which is strongly associated with MC1R polymorphisms. MC1R expression is modulated by endocrine sex hormones; melanocyte regulation in the trunk may have hormone-related features since distribution is different between males and females [48]. …”

Diferenças Clínico-Epidemiológicas entre Pacientes Masculinos e Femininos com Diagnóstico de Melanoma Cutâneo no Oeste de Santa Catarina

“…estar casado e possuir maiores níveis de escolaridade estão relacionados com melhores escores de qualidade de vida em pacientes com Mc 16 . Fatores relacionados ao aumento do risco de Mc incluem baixo nível socioeconômico e menor escolaridade, além de percepções incipientes acerca dos Mc correlacionaram-se com aumento da morbidade e mortalidade em pacientes portadores da neoplasia 17 . os dados coletados relacionados com os pacientes incluídos na amostra podem ser comuns à população residente na região e não exclusivos dos pacientes que desenvolveram Mc.…”

“…o Mes tem sido relatado como o mais prevalente, independente do sexo [11][12][13][14][15][16][17][18][19][20][21] , seguido do Mn [11][12][13][14][15][16][17][18][19][20][21][22] ; o que foi também verificado no presente estudo. a maior prevalência de Mn em homens pode ser uma das explicações para o maior risco de morte por Mc em relação às mulheres, pois a presença de Mn aumenta em 1,5 vezes a mortalidade quando comparado ao Mes 11 , sendo esse risco independe entre homens e mulheres 24 .…”