Inherited MC 1R variants in patients with melanoma are associated with better survival in women

Abstract

Summary Background Women have a better melanoma prognosis, and fairer skin/hair colour. The presence of inherited MC1R variants has been associated with a better melanoma prognosis, but its interaction with sex is unknown. Objectives To evaluate the relationship between germline MC1R status and survival, and determine any association with sex. Methods This was a cohort study including 1341 patients with melanoma from the Melanoma Unit of the Hospital Clinic of Barcelona, between January 1996 and April 2018. We examined known sex‐related prognosis factors as they relate to features of melanoma and evaluated the sex‐specific role of MC1R in overall and melanoma‐specific survival. Hazard ratios (HRs) were calculated using univariate and multivariate Cox logistic regression. Results Men showed lower overall survival than women (P < 0·001) and the presence of inherited MC1R variants was not associated with better survival in our cohort. However, in women the presence of MC1R variants was associated with better overall survival in the multivariate analysis [HR 0·57, 95% confidence interval (CI) 0·38–0·85; P = 0·006] but not in men [HR 1·26, 95% CI 0·89–1·79; P = 0·185 (P‐value for interaction 0·004)]. Analysis performed for melanoma‐specific survival showed the same level of significance. Conclusions Inherited MC1R variants are associated with improved overall survival in women with melanoma but not in men. Intrinsic sex‐dependent features can modify the role of specific genes in melanoma prognosis. We believe that survival studies of patients with melanoma should include analysis by sex and MC1R genotype. What's already known about this topic? Inherited MC1R variants have been associated with a better melanoma prognosis, but their interaction with sex is unknown. What does this study add? MC1R variants are related to better overall survival and melanoma‐specific survival in women but not in men. What is the translational message? These differences between the sexes could imply future changes in melanoma follow‐up and treatment strategies. This provides a basis for understanding the interaction between sex‐related genes and germline variants in cancer.

Incidence of Melanoma in Catalonia, Spain, Is Rapidly Increasing in the Elderly Population. A Multicentric Cohort Study

“…One biological explanation for this difference could be related to the hormonal profile. It has been seen that high levels of oestrogen during a woman’s fertile period can promote the formation of reactive oxygen species which seem to favour the development of melanoma seen in younger women [ 40 ].…”

New biomarkers improve stratification of patients with melanoma

“…In their study, Lira et al . hypothesize that MC1R status might influence survival of men and women differently . To test this hypothesis, they analysed > 1000 patients from a cohort with melanoma from Barcelona, and correlated MC1R status to outcome.…”

“…The first study, by Lira et al, explores how the melanocortin 1 receptor (MC1R) gene affects melanoma survival. 3 MC1R is a highly variable gene that regulates skin, hair colour and photosensitivity; and identifies a subset of the population at higher risk of melanoma. Germline variants in the gene most strongly associated with a fair complexion are termed 'R' variants, and variants conferring a weaker phenotype are defined as 'r' variants.…”

“…5 In their study, Lira et al hypothesize that MC1R status might influence survival of men and women differently. 3 To test this hypothesis, they analysed > 1000 patients from a cohort with melanoma from Barcelona, and correlated MC1R status to outcome. Their cohort is well balanced for age, skin phototype and Breslow, and differs only in the previously observed differences in anatomic site of the primary melanoma between sexes (men more trunk and women more lower limb disease) and ulceration.…”

“…The first study, by Lira et al ., explores how the melanocortin 1 receptor ( MC1R ) gene affects melanoma survival . MC1R is a highly variable gene that regulates skin, hair colour and photosensitivity; and identifies a subset of the population at higher risk of melanoma.…”