Distribution of MC1R variants among melanoma subtypes: p.R163Q is associated with lentigo maligna melanoma in a Mediterranean population
LINK: https://doi.org/10.1111/bjd.12418
Funding sources The research at
the Melanoma Unit in Barcelona was partially funded by Grants 03/0019, 05/0302,
06/0265 and 09/01393 from Fondo de Investigaciones Sanitarias, Spain; by the
CIBER de Enfermedades Raras of the Instituto de Salud Carlos III, Spain; by the
AGAUR 2009 SGR 1337 of the Catalan Government, Spain; by the European
Commission under the 6th Framework Programme, contract no. LSHC‐CT‐2006‐018702 (GenoMEL) and by the National Cancer Institute of the U.S.
National Institutes of Health (CA83115). The work was carried out at the Esther
Koplowitz Centre, Barcelona, Spain. The samples from the Instituto Valenciano de Oncología were collected
from the Biobanco del Instituto Valenciano de Oncología.
Background
Cutaneous melanoma tumour is classified into clinicohistopathological
subtypes that may be associated with different genetic and host factors.
Variation in the MC1R gene is one of the main factors of risk
variation in sporadic melanoma. The relationship between MC1R variants
and the risk of developing a specific subtype of melanoma has not been
previously explored.
Objectives
To analyse whether certain MC1R variants
are associated with particular melanoma subtypes with specific
clinicohistopathological features.
Methods
An association study was performed between MC1R gene
variants and clinicopathological subtypes of primary melanoma derived from 1679
patients.
Results
We detected 53 MC1R variants (11
synonymous and 42 nonsynonymous). Recurrent nonsynonymous variants were p.V60L
(30·0%), p.V92M (11·7%), p.D294H (9·4%), p.R151C (8·8%), p.R160W (6·2%),
p.R163Q (4·2%) p.R142H (3·3%), p.I155T (3·8%), p.V122M (1·5%) and p.D84E
(1·0%). Melanoma subtypes showed differences in the total number of MC1R variants
(P = 0·028) and the number of red hair colour variants
(P = 0·035). Furthermore, an association between
p.R163Q and lentigo maligna melanoma was detected under a dominant model of
heritance (odds ratio 2·16, 95% confidence interval 1·07–4·37; P = 0·044).
No association was found between p.R163Q and Fitzpatrick skin phototype, eye
colour or skin colour, indicating that the association was independent of the
role of MC1R in pigmentation. No association was observed
between MC1R polymorphisms and other melanoma subtypes.
Conclusions
Our findings suggest that certain #MC1R variants
could increase melanoma risk due to their impact on pathways other than
pigmentation, and may therefore be linked to specific melanoma subtypes
#malvehy #susanapuig #cristinacarrera #paulaaguilera #jmalvehy #melanoma #skincancer #mc1r #genomel
J.A. Puig‐Butillé C. Carrera R. Kumar Z. Garcia‐Casado P. Aguilera J. Malvehy E. Nagore S. Pui
