MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: A pooled-analysis from the M-SKIP project

M-SKIP Study Group

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

The MC1R gene is a key regulator of skin pigmentation. We aimed to evaluate the association between MC1R variants and the risk of sporadic cutaneous melanoma (CM) within the M-SKIP project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. Data included 5,160 cases and 12,119 controls from 17 studies. We calculated a summary odds ratio (SOR) for the association of each of the nine most studied MC1R variants and of variants combined with CM by using random-effects models. Stratified analysis by phenotypic characteristics were also performed. Melanoma risk increased with presence of any of the main MC1R variants: the SOR for each variant ranged from 1.47 (95%CI: 1.17-1.84) for V60L to 2.74 (1.53-4.89) for D84E. Carriers of any MC1R variant had a 66% higher risk of developing melanoma compared with wildtype subjects (SOR; 95%CI: 1.66; 1.41-1.96) and the risk attributable to MC1R variants was 28%. When taking into account phenotypic characteristics, we found that MC1R-associated melanoma risk increased only for darker-pigmented Caucasians: SOR (95%CI) was 3.14 (2.06-4.80) for subjects with no freckles, no red hair and skin Type III/IV. Our study documents the important role of all the main MC1R variants in sporadic CM and suggests that they have a direct effect on melanoma risk, independently on the phenotypic characteristics of carriers. This is of particular importance for assessing preventive strategies, which may be directed to darker-pigmented Caucasians with MC1R variants as well as to lightly pigmented, fairskinned subjects.

Original languageEnglish
Pages (from-to)618-631
Number of pages14
JournalInternational Journal of Cancer
Volume136
Issue number3
DOIs
Publication statusPublished - 2015 Feb 15

Keywords

  • Genetic epidemiology
  • Melanocortin-1 receptor
  • Melanoma
  • Meta-analysis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians : A pooled-analysis from the M-SKIP project. / M-SKIP Study Group.

In: International Journal of Cancer, Vol. 136, No. 3, 15.02.2015, p. 618-631.

Research output: Contribution to journalArticle

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title = "MC1R variants increased the risk of sporadic cutaneous melanoma in darker-pigmented Caucasians: A pooled-analysis from the M-SKIP project",
abstract = "The MC1R gene is a key regulator of skin pigmentation. We aimed to evaluate the association between MC1R variants and the risk of sporadic cutaneous melanoma (CM) within the M-SKIP project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. Data included 5,160 cases and 12,119 controls from 17 studies. We calculated a summary odds ratio (SOR) for the association of each of the nine most studied MC1R variants and of variants combined with CM by using random-effects models. Stratified analysis by phenotypic characteristics were also performed. Melanoma risk increased with presence of any of the main MC1R variants: the SOR for each variant ranged from 1.47 (95{\%}CI: 1.17-1.84) for V60L to 2.74 (1.53-4.89) for D84E. Carriers of any MC1R variant had a 66{\%} higher risk of developing melanoma compared with wildtype subjects (SOR; 95{\%}CI: 1.66; 1.41-1.96) and the risk attributable to MC1R variants was 28{\%}. When taking into account phenotypic characteristics, we found that MC1R-associated melanoma risk increased only for darker-pigmented Caucasians: SOR (95{\%}CI) was 3.14 (2.06-4.80) for subjects with no freckles, no red hair and skin Type III/IV. Our study documents the important role of all the main MC1R variants in sporadic CM and suggests that they have a direct effect on melanoma risk, independently on the phenotypic characteristics of carriers. This is of particular importance for assessing preventive strategies, which may be directed to darker-pigmented Caucasians with MC1R variants as well as to lightly pigmented, fairskinned subjects.",
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author = "{M-SKIP Study Group} and Elena Pasquali and Garc{\'i}a-Borr{\'o}n, {Jos{\'e} C.} and Fargnoli, {Maria Concetta} and Sara Gandini and Patrick Maisonneuve and Vincenzo Bagnardi and Claudia Specchia and Fan Liu and Manfred Kayser and Tamar Nijsten and Eduardo Nagore and Rajiv Kumar and Johan Hansson and Kanetsky, {Peter A.} and Paola Ghiorzo and Tadeusz Debniak and Wojciech Branicki and Gruis, {Nelleke A.} and Jiali Han and Terry Dwyer and Leigh Blizzard and Landi, {Maria Teresa} and Giuseppe Palmieri and Gloria Ribas and Alexander Stratigos and Council, {M. Laurin} and Philippe Autier and Julian Little and Julia Newton-Bishop and Francesco Sera and Sara Raimondi and Saverio Caini and Albert Hofman and Uitterlinden, {Andre G.} and Dominique Scherer and Veronica Hoiom and Lorenza Pastorino and Jennifer Cochrane and Ricardo Fernandez-De-Misa and Niels Morling and Peter Johansen and Ruth Pfeiffer and Katerina Kypreou and Anne Bowcock and Lynn Cornelius and Tomonori Motokawa and Sumiko Anno and Per Helsing and Andresen, {Per Arne} and Wong, {Terence H.}",
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T2 - A pooled-analysis from the M-SKIP project

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AU - Pasquali, Elena

AU - García-Borrón, José C.

AU - Fargnoli, Maria Concetta

AU - Gandini, Sara

AU - Maisonneuve, Patrick

AU - Bagnardi, Vincenzo

AU - Specchia, Claudia

AU - Liu, Fan

AU - Kayser, Manfred

AU - Nijsten, Tamar

AU - Nagore, Eduardo

AU - Kumar, Rajiv

AU - Hansson, Johan

AU - Kanetsky, Peter A.

AU - Ghiorzo, Paola

AU - Debniak, Tadeusz

AU - Branicki, Wojciech

AU - Gruis, Nelleke A.

AU - Han, Jiali

AU - Dwyer, Terry

AU - Blizzard, Leigh

AU - Landi, Maria Teresa

AU - Palmieri, Giuseppe

AU - Ribas, Gloria

AU - Stratigos, Alexander

AU - Council, M. Laurin

AU - Autier, Philippe

AU - Little, Julian

AU - Newton-Bishop, Julia

AU - Sera, Francesco

AU - Raimondi, Sara

AU - Caini, Saverio

AU - Hofman, Albert

AU - Uitterlinden, Andre G.

AU - Scherer, Dominique

AU - Hoiom, Veronica

AU - Pastorino, Lorenza

AU - Cochrane, Jennifer

AU - Fernandez-De-Misa, Ricardo

AU - Morling, Niels

AU - Johansen, Peter

AU - Pfeiffer, Ruth

AU - Kypreou, Katerina

AU - Bowcock, Anne

AU - Cornelius, Lynn

AU - Motokawa, Tomonori

AU - Anno, Sumiko

AU - Helsing, Per

AU - Andresen, Per Arne

AU - Wong, Terence H.

PY - 2015/2/15

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N2 - The MC1R gene is a key regulator of skin pigmentation. We aimed to evaluate the association between MC1R variants and the risk of sporadic cutaneous melanoma (CM) within the M-SKIP project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. Data included 5,160 cases and 12,119 controls from 17 studies. We calculated a summary odds ratio (SOR) for the association of each of the nine most studied MC1R variants and of variants combined with CM by using random-effects models. Stratified analysis by phenotypic characteristics were also performed. Melanoma risk increased with presence of any of the main MC1R variants: the SOR for each variant ranged from 1.47 (95%CI: 1.17-1.84) for V60L to 2.74 (1.53-4.89) for D84E. Carriers of any MC1R variant had a 66% higher risk of developing melanoma compared with wildtype subjects (SOR; 95%CI: 1.66; 1.41-1.96) and the risk attributable to MC1R variants was 28%. When taking into account phenotypic characteristics, we found that MC1R-associated melanoma risk increased only for darker-pigmented Caucasians: SOR (95%CI) was 3.14 (2.06-4.80) for subjects with no freckles, no red hair and skin Type III/IV. Our study documents the important role of all the main MC1R variants in sporadic CM and suggests that they have a direct effect on melanoma risk, independently on the phenotypic characteristics of carriers. This is of particular importance for assessing preventive strategies, which may be directed to darker-pigmented Caucasians with MC1R variants as well as to lightly pigmented, fairskinned subjects.

AB - The MC1R gene is a key regulator of skin pigmentation. We aimed to evaluate the association between MC1R variants and the risk of sporadic cutaneous melanoma (CM) within the M-SKIP project, an international pooled-analysis on MC1R, skin cancer and phenotypic characteristics. Data included 5,160 cases and 12,119 controls from 17 studies. We calculated a summary odds ratio (SOR) for the association of each of the nine most studied MC1R variants and of variants combined with CM by using random-effects models. Stratified analysis by phenotypic characteristics were also performed. Melanoma risk increased with presence of any of the main MC1R variants: the SOR for each variant ranged from 1.47 (95%CI: 1.17-1.84) for V60L to 2.74 (1.53-4.89) for D84E. Carriers of any MC1R variant had a 66% higher risk of developing melanoma compared with wildtype subjects (SOR; 95%CI: 1.66; 1.41-1.96) and the risk attributable to MC1R variants was 28%. When taking into account phenotypic characteristics, we found that MC1R-associated melanoma risk increased only for darker-pigmented Caucasians: SOR (95%CI) was 3.14 (2.06-4.80) for subjects with no freckles, no red hair and skin Type III/IV. Our study documents the important role of all the main MC1R variants in sporadic CM and suggests that they have a direct effect on melanoma risk, independently on the phenotypic characteristics of carriers. This is of particular importance for assessing preventive strategies, which may be directed to darker-pigmented Caucasians with MC1R variants as well as to lightly pigmented, fairskinned subjects.

KW - Genetic epidemiology

KW - Melanocortin-1 receptor

KW - Melanoma

KW - Meta-analysis

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