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MC1R gene variants and non-melanoma skin cancer: a pooled-analysis from the M-SKIP project

Identifieur interne : 003277 ( Main/Exploration ); précédent : 003276; suivant : 003278

MC1R gene variants and non-melanoma skin cancer: a pooled-analysis from the M-SKIP project

Auteurs : E. Tagliabue [Italie] ; M C Fargnoli [Italie] ; S. Gandini [Italie] ; P. Maisonneuve [Italie] ; F. Liu [Pays-Bas] ; M. Kayser [Pays-Bas] ; T. Nijsten [Pays-Bas] ; J. Han [États-Unis] ; R. Kumar [Allemagne] ; N A Gruis [Pays-Bas] ; L. Ferrucci [États-Unis] ; W. Branicki [Pologne] ; T. Dwyer [Australie] ; L. Blizzard [Australie] ; P. Helsing [Norvège] ; P. Autier [France] ; J C García-Borr N [Espagne] ; P A Kanetsky [États-Unis] ; M T Landi [États-Unis] ; J. Little [Canada] ; J. Newton-Bishop [Royaume-Uni] ; F. Sera [Royaume-Uni] ; S. Raimondi [Italie]

Source :

RBID : PMC:4506395

Descripteurs français

English descriptors

Abstract

Background:

The melanocortin-1-receptor (MC1R) gene regulates human pigmentation and is highly polymorphic in populations of European origins. The aims of this study were to evaluate the association between MC1R variants and the risk of non-melanoma skin cancer (NMSC), and to investigate whether risk estimates differed by phenotypic characteristics.

Methods:

Data on 3527 NMSC cases and 9391 controls were gathered through the M-SKIP Project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. We calculated summary odds ratios (SOR) with random-effect models, and performed stratified analyses.

Results:

Subjects carrying at least one MC1R variant had an increased risk of NMSC overall, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC): SOR (95%CI) were 1.48 (1.24–1.76), 1.39 (1.15–1.69) and 1.61 (1.35–1.91), respectively. All of the investigated variants showed positive associations with NMSC, with consistent significant results obtained for V60L, D84E, V92M, R151C, R160W, R163Q and D294H: SOR (95%CI) ranged from 1.42 (1.19–1.70) for V60L to 2.66 (1.06–6.65) for D84E variant. In stratified analysis, there was no consistent pattern of association between MC1R and NMSC by skin type, but we consistently observed higher SORs for subjects without red hair.

Conclusions:

Our pooled-analysis highlighted a role of MC1R variants in NMSC development and suggested an effect modification by red hair colour phenotype.


Url:
DOI: 10.1038/bjc.2015.231
PubMed: 26103569
PubMed Central: 4506395


Affiliations:


Links toward previous steps (curation, corpus...)


Le document en format XML

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gene variants and non-melanoma skin cancer: a pooled-analysis from the M-SKIP project</title>
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gene variants and non-melanoma skin cancer: a pooled-analysis from the M-SKIP project</title>
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</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
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</author>
<author>
<name sortKey="Ferrucci, L" sort="Ferrucci, L" uniqKey="Ferrucci L" first="L" last="Ferrucci">L. Ferrucci</name>
<affiliation wicri:level="1">
<nlm:aff id="aff10">
<institution>Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale Cancer Center</institution>
, New Haven, CT 06520-8034,
<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Branicki, W" sort="Branicki, W" uniqKey="Branicki W" first="W" last="Branicki">W. Branicki</name>
<affiliation wicri:level="1">
<nlm:aff id="aff11">
<institution>Institute of Forensic Research</institution>
, 31-033 Krakow,
<country>Poland</country>
</nlm:aff>
<country xml:lang="fr">Pologne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Dwyer, T" sort="Dwyer, T" uniqKey="Dwyer T" first="T" last="Dwyer">T. Dwyer</name>
<affiliation wicri:level="1">
<nlm:aff id="aff12">
<institution>Murdoch Childrens Research Institute, Royal Children's Hospital</institution>
, Victoria 3052,
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Blizzard, L" sort="Blizzard, L" uniqKey="Blizzard L" first="L" last="Blizzard">L. Blizzard</name>
<affiliation wicri:level="1">
<nlm:aff id="aff13">
<institution>Menzies Research Institute Tasmania, University of Tasmania</institution>
, Hobart, 7001
<country>Australia</country>
</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Helsing, P" sort="Helsing, P" uniqKey="Helsing P" first="P" last="Helsing">P. Helsing</name>
<affiliation wicri:level="1">
<nlm:aff id="aff14">
<institution>Department of Pathology, Oslo University Hospital</institution>
, N-0027 Oslo,
<country>Norway</country>
</nlm:aff>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Autier, P" sort="Autier, P" uniqKey="Autier P" first="P" last="Autier">P. Autier</name>
<affiliation wicri:level="1">
<nlm:aff id="aff15">
<institution>International Prevention Research Institute</institution>
, Lyon 69006,
<country>France</country>
</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Garcia Borr N, J C" sort="Garcia Borr N, J C" uniqKey="Garcia Borr N J" first="J C" last="García-Borr N">J C García-Borr N</name>
<affiliation wicri:level="1">
<nlm:aff id="aff16">
<institution>Department of Biochemistry, Molecular Biology and Immunology, University of Murcia</institution>
, 30100 Murcia,
<country>Spain</country>
</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Kanetsky, P A" sort="Kanetsky, P A" uniqKey="Kanetsky P" first="P A" last="Kanetsky">P A Kanetsky</name>
<affiliation wicri:level="1">
<nlm:aff id="aff17">
<institution>Department of Cancer Epidemiology, Moffitt Cancer Center</institution>
, Tampa, FL 33612,
<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Landi, M T" sort="Landi, M T" uniqKey="Landi M" first="M T" last="Landi">M T Landi</name>
<affiliation wicri:level="1">
<nlm:aff id="aff18">
<institution>Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH</institution>
, Bethesda, MD 20892-7236,
<country>USA</country>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Little, J" sort="Little, J" uniqKey="Little J" first="J" last="Little">J. Little</name>
<affiliation wicri:level="1">
<nlm:aff id="aff19">
<institution>School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa</institution>
, Ottawa,
<country>Canada</country>
ON K1N 6N5</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Newton Bishop, J" sort="Newton Bishop, J" uniqKey="Newton Bishop J" first="J" last="Newton-Bishop">J. Newton-Bishop</name>
<affiliation wicri:level="1">
<nlm:aff id="aff20">
<institution>Section of Epidemiology and Biostatistics, Institute of Cancer and Pathology, University of Leeds</institution>
, Leeds LS9 7TF,
<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Sera, F" sort="Sera, F" uniqKey="Sera F" first="F" last="Sera">F. Sera</name>
<affiliation wicri:level="1">
<nlm:aff id="aff21">
<institution>UCL Institute of Child Health</institution>
, London WC1N 1EH,
<country>UK</country>
</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
<author>
<name sortKey="Raimondi, S" sort="Raimondi, S" uniqKey="Raimondi S" first="S" last="Raimondi">S. Raimondi</name>
<affiliation wicri:level="1">
<nlm:aff id="aff1">
<institution>Division of Epidemiology and Biostatistics, European Institute of Oncology</institution>
, Via Ripamonti 435, Milan 20141,
<country>Italy</country>
</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea># see nlm:aff country strict</wicri:regionArea>
</affiliation>
</author>
</analytic>
<series>
<title level="j">British Journal of Cancer</title>
<idno type="ISSN">0007-0920</idno>
<idno type="eISSN">1532-1827</idno>
<imprint>
<date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Carcinoma, Basal Cell (genetics)</term>
<term>Carcinoma, Squamous Cell (genetics)</term>
<term>Genetic Predisposition to Disease</term>
<term>Hair Color</term>
<term>Humans</term>
<term>Odds Ratio</term>
<term>Phenotype</term>
<term>Receptor, Melanocortin, Type 1 (genetics)</term>
<term>Risk</term>
<term>Skin Neoplasms (etiology)</term>
<term>Skin Neoplasms (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Carcinome basocellulaire (génétique)</term>
<term>Carcinome épidermoïde (génétique)</term>
<term>Couleur des cheveux</term>
<term>Humains</term>
<term>Odds ratio</term>
<term>Phénotype</term>
<term>Prédisposition génétique à une maladie</term>
<term>Risque</term>
<term>Récepteur de la mélanocortine de type 1 (génétique)</term>
<term>Tumeurs cutanées (génétique)</term>
<term>Tumeurs cutanées (étiologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en">
<term>Receptor, Melanocortin, Type 1</term>
</keywords>
<keywords scheme="MESH" qualifier="etiology" xml:lang="en">
<term>Skin Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Carcinoma, Basal Cell</term>
<term>Carcinoma, Squamous Cell</term>
<term>Skin Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Carcinome basocellulaire</term>
<term>Carcinome épidermoïde</term>
<term>Récepteur de la mélanocortine de type 1</term>
<term>Tumeurs cutanées</term>
</keywords>
<keywords scheme="MESH" qualifier="étiologie" xml:lang="fr">
<term>Tumeurs cutanées</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Genetic Predisposition to Disease</term>
<term>Hair Color</term>
<term>Humans</term>
<term>Odds Ratio</term>
<term>Phenotype</term>
<term>Risk</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Couleur des cheveux</term>
<term>Humains</term>
<term>Odds ratio</term>
<term>Phénotype</term>
<term>Prédisposition génétique à une maladie</term>
<term>Risque</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<sec>
<title>Background:</title>
<p>The melanocortin-1-receptor (
<italic>MC1R</italic>
) gene regulates human pigmentation and is highly polymorphic in populations of European origins. The aims of this study were to evaluate the association between
<italic>MC1R</italic>
variants and the risk of non-melanoma skin cancer (NMSC), and to investigate whether risk estimates differed by phenotypic characteristics.</p>
</sec>
<sec>
<title>Methods:</title>
<p>Data on 3527 NMSC cases and 9391 controls were gathered through the M-SKIP Project, an international pooled-analysis on
<italic>MC1R</italic>
, skin cancer and phenotypic characteristics. We calculated summary odds ratios (SOR) with random-effect models, and performed stratified analyses.</p>
</sec>
<sec>
<title>Results:</title>
<p>Subjects carrying at least one
<italic>MC1R</italic>
variant had an increased risk of NMSC overall, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC): SOR (95%CI) were 1.48 (1.24–1.76), 1.39 (1.15–1.69) and 1.61 (1.35–1.91), respectively. All of the investigated variants showed positive associations with NMSC, with consistent significant results obtained for V60L, D84E, V92M, R151C, R160W, R163Q and D294H: SOR (95%CI) ranged from 1.42 (1.19–1.70) for V60L to 2.66 (1.06–6.65) for D84E variant. In stratified analysis, there was no consistent pattern of association between
<italic>MC1R</italic>
and NMSC by skin type, but we consistently observed higher SORs for subjects without red hair.</p>
</sec>
<sec>
<title>Conclusions:</title>
<p>Our pooled-analysis highlighted a role of
<italic>MC1R</italic>
variants in NMSC development and suggested an effect modification by red hair colour phenotype.</p>
</sec>
</div>
</front>
<back>
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