MC1R gene variants and non-melanoma skin cancer

A pooled-analysis from the M-SKIP project

E. Tagliabue, M. C. Fargnoli, S. Gandini, P. Maisonneuve, F. Liu, M. Kayser, T. Nijsten, J. Han, R. Kumar, N. A. Gruis, L. Ferrucci, W. Branicki, T. Dwyer, L. Blizzard, P. Helsing, P. Autier, J. C. García-Borrón, P. A. Kanetsky, M. T. Landi, J. Little & 111 others J. Newton-Bishop, F. Sera, S. Raimondi, Sara Raimondi, Philippe Autier, Maria Concetta Fargnoli, José C. García-Borrón, Jiali Han, Peter A. Kanetsky, Maria Teresa Landi, Julian Little, Julia Newton-Bishop, Francesco Sera, Saverio Caini, Sara Gandini, Patrick Maisonneuve, Albert Hofman, Manfred Kayser, Fan Liu, Tamar Nijsten, Andre G. Uitterlinden, Rajiv Kumar, Dominique Scherer, Eduardo Nagore, Johan Hansson, Veronica Hoiom, Paola Ghiorzo, Lorenza Pastorino, Nelleke A. Gruis, Jan Nico Bouwes Bavinck, Paula Aguilera, Celia Badenas, Cristina Carrera, Josep Malvehy, Miriam Potrony Mateu, Susana Puig, Joan Anton Puig-Butille, Gemma Tell, Terence Dwyer, Leigh Blizzard, Jennifer Cochrane, Ricardo Fernandez-De-Misa, Wojciech Branicki, Tadeusz Debniak, Niels Morling, Peter Johansen, Susan Mayne, Allen Bale, Brenda Cartmel, Leah Ferrucci, Ruth Pfeiffer, Sumiko Anno, Gloria Ribas, Alexander Stratigos, Katerina Kypreou, Anne Bowcock, Lynn Cornelius, M. Laurin Council, Tomonori Motokawa, Sumiko Anno, Per Helsing, Per Arne Andresen, Terence H. Wong, Marianne Berwick, Irene Orlow, Urvi Mujumdar, Amanda Hummer, Klaus Busam, Pampa Roy, Rebecca Canchola, Brian Clas, Javiar Cotignola, Yvette Monroe, Bruce Armstrong, Anne Kricker, Melisa Litchfield, Terence Dwye, Paul Tucker, Nicola Stephens, Richard Gallagher, Teresa Switzer, Loraine Marrett, Beth Theis, Lynn From, Noori Chowdhury, Louise Vanasse, Mark Purdue, David Northrup, Roberto Zanetti, Stefano Rosso, Carlotta Sacerdote, Hoda Anton-Culver, Nancy Leighton, Maureen Gildea, Stephen Gruber, Joe Bonner, Joanne Jeter, Judith Klotz, Homer Wilcox, Helen Weiss, Robert Millikan, Nancy Thomas, Dianne Mattingly, Jon Player, Chiu Kit Tse, Timothy Rebbeck, Peter P. Kanetsky, Amy Walker, Saarene Panossian, Harvey Mohrenweiser, Richard Setlow

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)354-363
Number of pages10
JournalBritish Journal of Cancer
Volume113
Issue number2
DOIs
Publication statusPublished - 2015 Jul 14

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Tagliabue, E., Fargnoli, M. C., Gandini, S., Maisonneuve, P., Liu, F., Kayser, M., ... Setlow, R. (2015). MC1R gene variants and non-melanoma skin cancer: A pooled-analysis from the M-SKIP project. British Journal of Cancer, 113(2), 354-363. https://doi.org/10.1038/bjc.2015.231

MC1R gene variants and non-melanoma skin cancer : A pooled-analysis from the M-SKIP project. / Tagliabue, E.; Fargnoli, M. C.; Gandini, S.; Maisonneuve, P.; Liu, F.; Kayser, M.; Nijsten, T.; Han, J.; Kumar, R.; Gruis, N. A.; Ferrucci, L.; Branicki, W.; Dwyer, T.; Blizzard, L.; Helsing, P.; Autier, P.; García-Borrón, J. C.; Kanetsky, P. A.; Landi, M. T.; Little, J.; Newton-Bishop, J.; Sera, F.; Raimondi, S.; Raimondi, Sara; Autier, Philippe; Fargnoli, Maria Concetta; García-Borrón, José C.; Han, Jiali; Kanetsky, Peter A.; Landi, Maria Teresa; Little, Julian; Newton-Bishop, Julia; Sera, Francesco; Caini, Saverio; Gandini, Sara; Maisonneuve, Patrick; Hofman, Albert; Kayser, Manfred; Liu, Fan; Nijsten, Tamar; Uitterlinden, Andre G.; Kumar, Rajiv; Scherer, Dominique; Nagore, Eduardo; Hansson, Johan; Hoiom, Veronica; Ghiorzo, Paola; Pastorino, Lorenza; Gruis, Nelleke A.; Bavinck, Jan Nico Bouwes; Aguilera, Paula; Badenas, Celia; Carrera, Cristina; Malvehy, Josep; Mateu, Miriam Potrony; Puig, Susana; Puig-Butille, Joan Anton; Tell, Gemma; Dwyer, Terence; Blizzard, Leigh; Cochrane, Jennifer; Fernandez-De-Misa, Ricardo; Branicki, Wojciech; Debniak, Tadeusz; Morling, Niels; Johansen, Peter; Mayne, Susan; Bale, Allen; Cartmel, Brenda; Ferrucci, Leah; Pfeiffer, Ruth; Anno, Sumiko; Ribas, Gloria; Stratigos, Alexander; Kypreou, Katerina; Bowcock, Anne; Cornelius, Lynn; Council, M. Laurin; Motokawa, Tomonori; Anno, Sumiko; Helsing, Per; Andresen, Per Arne; Wong, Terence H.; Berwick, Marianne; Orlow, Irene; Mujumdar, Urvi; Hummer, Amanda; Busam, Klaus; Roy, Pampa; Canchola, Rebecca; Clas, Brian; Cotignola, Javiar; Monroe, Yvette; Armstrong, Bruce; Kricker, Anne; Litchfield, Melisa; Dwye, Terence; Tucker, Paul; Stephens, Nicola; Gallagher, Richard; Switzer, Teresa; Marrett, Loraine; Theis, Beth; From, Lynn; Chowdhury, Noori; Vanasse, Louise; Purdue, Mark; Northrup, David; Zanetti, Roberto; Rosso, Stefano; Sacerdote, Carlotta; Anton-Culver, Hoda; Leighton, Nancy; Gildea, Maureen; Gruber, Stephen; Bonner, Joe; Jeter, Joanne; Klotz, Judith; Wilcox, Homer; Weiss, Helen; Millikan, Robert; Thomas, Nancy; Mattingly, Dianne; Player, Jon; Tse, Chiu Kit; Rebbeck, Timothy; Kanetsky, Peter P.; Walker, Amy; Panossian, Saarene; Mohrenweiser, Harvey; Setlow, Richard.

In: British Journal of Cancer, Vol. 113, No. 2, 14.07.2015, p. 354-363.

Research output: Contribution to journalArticle

Tagliabue, E, Fargnoli, MC, Gandini, S, Maisonneuve, P, Liu, F, Kayser, M, Nijsten, T, Han, J, Kumar, R, Gruis, NA, Ferrucci, L, Branicki, W, Dwyer, T, Blizzard, L, Helsing, P, Autier, P, García-Borrón, JC, Kanetsky, PA, Landi, MT, Little, J, Newton-Bishop, J, Sera, F, Raimondi, S, Raimondi, S, Autier, P, Fargnoli, MC, García-Borrón, JC, Han, J, Kanetsky, PA, Landi, MT, Little, J, Newton-Bishop, J, Sera, F, Caini, S, Gandini, S, Maisonneuve, P, Hofman, A, Kayser, M, Liu, F, Nijsten, T, Uitterlinden, AG, Kumar, R, Scherer, D, Nagore, E, Hansson, J, Hoiom, V, Ghiorzo, P, Pastorino, L, Gruis, NA, Bavinck, JNB, Aguilera, P, Badenas, C, Carrera, C, Malvehy, J, Mateu, MP, Puig, S, Puig-Butille, JA, Tell, G, Dwyer, T, Blizzard, L, Cochrane, J, Fernandez-De-Misa, R, Branicki, W, Debniak, T, Morling, N, Johansen, P, Mayne, S, Bale, A, Cartmel, B, Ferrucci, L, Pfeiffer, R, Anno, S, Ribas, G, Stratigos, A, Kypreou, K, Bowcock, A, Cornelius, L, Council, ML, Motokawa, T, Anno, S, Helsing, P, Andresen, PA, Wong, TH, Berwick, M, Orlow, I, Mujumdar, U, Hummer, A, Busam, K, Roy, P, Canchola, R, Clas, B, Cotignola, J, Monroe, Y, Armstrong, B, Kricker, A, Litchfield, M, Dwye, T, Tucker, P, Stephens, N, Gallagher, R, Switzer, T, Marrett, L, Theis, B, From, L, Chowdhury, N, Vanasse, L, Purdue, M, Northrup, D, Zanetti, R, Rosso, S, Sacerdote, C, Anton-Culver, H, Leighton, N, Gildea, M, Gruber, S, Bonner, J, Jeter, J, Klotz, J, Wilcox, H, Weiss, H, Millikan, R, Thomas, N, Mattingly, D, Player, J, Tse, CK, Rebbeck, T, Kanetsky, PP, Walker, A, Panossian, S, Mohrenweiser, H & Setlow, R 2015, 'MC1R gene variants and non-melanoma skin cancer: A pooled-analysis from the M-SKIP project', British Journal of Cancer, vol. 113, no. 2, pp. 354-363. https://doi.org/10.1038/bjc.2015.231
Tagliabue E, Fargnoli MC, Gandini S, Maisonneuve P, Liu F, Kayser M et al. MC1R gene variants and non-melanoma skin cancer: A pooled-analysis from the M-SKIP project. British Journal of Cancer. 2015 Jul 14;113(2):354-363. https://doi.org/10.1038/bjc.2015.231
Tagliabue, E. ; Fargnoli, M. C. ; Gandini, S. ; Maisonneuve, P. ; Liu, F. ; Kayser, M. ; Nijsten, T. ; Han, J. ; Kumar, R. ; Gruis, N. A. ; Ferrucci, L. ; Branicki, W. ; Dwyer, T. ; Blizzard, L. ; Helsing, P. ; Autier, P. ; García-Borrón, J. C. ; Kanetsky, P. A. ; Landi, M. T. ; Little, J. ; Newton-Bishop, J. ; Sera, F. ; Raimondi, S. ; Raimondi, Sara ; Autier, Philippe ; Fargnoli, Maria Concetta ; García-Borrón, José C. ; Han, Jiali ; Kanetsky, Peter A. ; Landi, Maria Teresa ; Little, Julian ; Newton-Bishop, Julia ; Sera, Francesco ; Caini, Saverio ; Gandini, Sara ; Maisonneuve, Patrick ; Hofman, Albert ; Kayser, Manfred ; Liu, Fan ; Nijsten, Tamar ; Uitterlinden, Andre G. ; Kumar, Rajiv ; Scherer, Dominique ; Nagore, Eduardo ; Hansson, Johan ; Hoiom, Veronica ; Ghiorzo, Paola ; Pastorino, Lorenza ; Gruis, Nelleke A. ; Bavinck, Jan Nico Bouwes ; Aguilera, Paula ; Badenas, Celia ; Carrera, Cristina ; Malvehy, Josep ; Mateu, Miriam Potrony ; Puig, Susana ; Puig-Butille, Joan Anton ; Tell, Gemma ; Dwyer, Terence ; Blizzard, Leigh ; Cochrane, Jennifer ; Fernandez-De-Misa, Ricardo ; Branicki, Wojciech ; Debniak, Tadeusz ; Morling, Niels ; Johansen, Peter ; Mayne, Susan ; Bale, Allen ; Cartmel, Brenda ; Ferrucci, Leah ; Pfeiffer, Ruth ; Anno, Sumiko ; Ribas, Gloria ; Stratigos, Alexander ; Kypreou, Katerina ; Bowcock, Anne ; Cornelius, Lynn ; Council, M. Laurin ; Motokawa, Tomonori ; Anno, Sumiko ; Helsing, Per ; Andresen, Per Arne ; Wong, Terence H. ; Berwick, Marianne ; Orlow, Irene ; Mujumdar, Urvi ; Hummer, Amanda ; Busam, Klaus ; Roy, Pampa ; Canchola, Rebecca ; Clas, Brian ; Cotignola, Javiar ; Monroe, Yvette ; Armstrong, Bruce ; Kricker, Anne ; Litchfield, Melisa ; Dwye, Terence ; Tucker, Paul ; Stephens, Nicola ; Gallagher, Richard ; Switzer, Teresa ; Marrett, Loraine ; Theis, Beth ; From, Lynn ; Chowdhury, Noori ; Vanasse, Louise ; Purdue, Mark ; Northrup, David ; Zanetti, Roberto ; Rosso, Stefano ; Sacerdote, Carlotta ; Anton-Culver, Hoda ; Leighton, Nancy ; Gildea, Maureen ; Gruber, Stephen ; Bonner, Joe ; Jeter, Joanne ; Klotz, Judith ; Wilcox, Homer ; Weiss, Helen ; Millikan, Robert ; Thomas, Nancy ; Mattingly, Dianne ; Player, Jon ; Tse, Chiu Kit ; Rebbeck, Timothy ; Kanetsky, Peter P. ; Walker, Amy ; Panossian, Saarene ; Mohrenweiser, Harvey ; Setlow, Richard. / MC1R gene variants and non-melanoma skin cancer : A pooled-analysis from the M-SKIP project. In: British Journal of Cancer. 2015 ; Vol. 113, No. 2. pp. 354-363.
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title = "MC1R gene variants and non-melanoma skin cancer: A pooled-analysis from the M-SKIP project",
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.",
author = "E. Tagliabue and Fargnoli, {M. C.} and S. Gandini and P. Maisonneuve and F. Liu and M. Kayser and T. Nijsten and J. Han and R. Kumar and Gruis, {N. A.} and L. Ferrucci and W. Branicki and T. Dwyer and L. Blizzard and P. Helsing and P. Autier and Garc{\'i}a-Borr{\'o}n, {J. C.} and Kanetsky, {P. A.} and Landi, {M. T.} and J. Little and J. Newton-Bishop and F. Sera and S. Raimondi and Sara Raimondi and Philippe Autier and Fargnoli, {Maria Concetta} and Garc{\'i}a-Borr{\'o}n, {Jos{\'e} C.} and Jiali Han and Kanetsky, {Peter A.} and Landi, {Maria Teresa} and Julian Little and Julia Newton-Bishop and Francesco Sera and Saverio Caini and Sara Gandini and Patrick Maisonneuve and Albert Hofman and Manfred Kayser and Fan Liu and Tamar Nijsten and Uitterlinden, {Andre G.} and Rajiv Kumar and Dominique Scherer and Eduardo Nagore and Johan Hansson and Veronica Hoiom and Paola Ghiorzo and Lorenza Pastorino and Gruis, {Nelleke A.} and Bavinck, {Jan Nico Bouwes} and Paula Aguilera and Celia Badenas and Cristina Carrera and Josep Malvehy and Mateu, {Miriam Potrony} and Susana Puig and Puig-Butille, {Joan Anton} and Gemma Tell and Terence Dwyer and Leigh Blizzard and Jennifer Cochrane and Ricardo Fernandez-De-Misa and Wojciech Branicki and Tadeusz Debniak and Niels Morling and Peter Johansen and Susan Mayne and Allen Bale and Brenda Cartmel and Leah Ferrucci and Ruth Pfeiffer and Sumiko Anno and Gloria Ribas and Alexander Stratigos and Katerina Kypreou and Anne Bowcock and Lynn Cornelius and Council, {M. Laurin} and Tomonori Motokawa and Sumiko Anno and Per Helsing and Andresen, {Per Arne} and Wong, {Terence H.} and Marianne Berwick and Irene Orlow and Urvi Mujumdar and Amanda Hummer and Klaus Busam and Pampa Roy and Rebecca Canchola and Brian Clas and Javiar Cotignola and Yvette Monroe and Bruce Armstrong and Anne Kricker and Melisa Litchfield and Terence Dwye and Paul Tucker and Nicola Stephens and Richard Gallagher and Teresa Switzer and Loraine Marrett and Beth Theis and Lynn From and Noori Chowdhury and Louise Vanasse and Mark Purdue and David Northrup and Roberto Zanetti and Stefano Rosso and Carlotta Sacerdote and Hoda Anton-Culver and Nancy Leighton and Maureen Gildea and Stephen Gruber and Joe Bonner and Joanne Jeter and Judith Klotz and Homer Wilcox and Helen Weiss and Robert Millikan and Nancy Thomas and Dianne Mattingly and Jon Player and Tse, {Chiu Kit} and Timothy Rebbeck and Kanetsky, {Peter P.} and Amy Walker and Saarene Panossian and Harvey Mohrenweiser and Richard Setlow",
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TY - JOUR

T1 - MC1R gene variants and non-melanoma skin cancer

T2 - A pooled-analysis from the M-SKIP project

AU - Tagliabue, E.

AU - Fargnoli, M. C.

AU - Gandini, S.

AU - Maisonneuve, P.

AU - Liu, F.

AU - Kayser, M.

AU - Nijsten, T.

AU - Han, J.

AU - Kumar, R.

AU - Gruis, N. A.

AU - Ferrucci, L.

AU - Branicki, W.

AU - Dwyer, T.

AU - Blizzard, L.

AU - Helsing, P.

AU - Autier, P.

AU - García-Borrón, J. C.

AU - Kanetsky, P. A.

AU - Landi, M. T.

AU - Little, J.

AU - Newton-Bishop, J.

AU - Sera, F.

AU - Raimondi, S.

AU - Raimondi, Sara

AU - Autier, Philippe

AU - Fargnoli, Maria Concetta

AU - García-Borrón, José C.

AU - Han, Jiali

AU - Kanetsky, Peter A.

AU - Landi, Maria Teresa

AU - Little, Julian

AU - Newton-Bishop, Julia

AU - Sera, Francesco

AU - Caini, Saverio

AU - Gandini, Sara

AU - Maisonneuve, Patrick

AU - Hofman, Albert

AU - Kayser, Manfred

AU - Liu, Fan

AU - Nijsten, Tamar

AU - Uitterlinden, Andre G.

AU - Kumar, Rajiv

AU - Scherer, Dominique

AU - Nagore, Eduardo

AU - Hansson, Johan

AU - Hoiom, Veronica

AU - Ghiorzo, Paola

AU - Pastorino, Lorenza

AU - Gruis, Nelleke A.

AU - Bavinck, Jan Nico Bouwes

AU - Aguilera, Paula

AU - Badenas, Celia

AU - Carrera, Cristina

AU - Malvehy, Josep

AU - Mateu, Miriam Potrony

AU - Puig, Susana

AU - Puig-Butille, Joan Anton

AU - Tell, Gemma

AU - Dwyer, Terence

AU - Blizzard, Leigh

AU - Cochrane, Jennifer

AU - Fernandez-De-Misa, Ricardo

AU - Branicki, Wojciech

AU - Debniak, Tadeusz

AU - Morling, Niels

AU - Johansen, Peter

AU - Mayne, Susan

AU - Bale, Allen

AU - Cartmel, Brenda

AU - Ferrucci, Leah

AU - Pfeiffer, Ruth

AU - Anno, Sumiko

AU - Ribas, Gloria

AU - Stratigos, Alexander

AU - Kypreou, Katerina

AU - Bowcock, Anne

AU - Cornelius, Lynn

AU - Council, M. Laurin

AU - Motokawa, Tomonori

AU - Anno, Sumiko

AU - Helsing, Per

AU - Andresen, Per Arne

AU - Wong, Terence H.

AU - Berwick, Marianne

AU - Orlow, Irene

AU - Mujumdar, Urvi

AU - Hummer, Amanda

AU - Busam, Klaus

AU - Roy, Pampa

AU - Canchola, Rebecca

AU - Clas, Brian

AU - Cotignola, Javiar

AU - Monroe, Yvette

AU - Armstrong, Bruce

AU - Kricker, Anne

AU - Litchfield, Melisa

AU - Dwye, Terence

AU - Tucker, Paul

AU - Stephens, Nicola

AU - Gallagher, Richard

AU - Switzer, Teresa

AU - Marrett, Loraine

AU - Theis, Beth

AU - From, Lynn

AU - Chowdhury, Noori

AU - Vanasse, Louise

AU - Purdue, Mark

AU - Northrup, David

AU - Zanetti, Roberto

AU - Rosso, Stefano

AU - Sacerdote, Carlotta

AU - Anton-Culver, Hoda

AU - Leighton, Nancy

AU - Gildea, Maureen

AU - Gruber, Stephen

AU - Bonner, Joe

AU - Jeter, Joanne

AU - Klotz, Judith

AU - Wilcox, Homer

AU - Weiss, Helen

AU - Millikan, Robert

AU - Thomas, Nancy

AU - Mattingly, Dianne

AU - Player, Jon

AU - Tse, Chiu Kit

AU - Rebbeck, Timothy

AU - Kanetsky, Peter P.

AU - Walker, Amy

AU - Panossian, Saarene

AU - Mohrenweiser, Harvey

AU - Setlow, Richard

PY - 2015/7/14

Y1 - 2015/7/14

N2 - 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.

AB - 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.

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U2 - 10.1038/bjc.2015.231

DO - 10.1038/bjc.2015.231

M3 - Article

VL - 113

SP - 354

EP - 363

JO - British Journal of Cancer

JF - British Journal of Cancer

SN - 0007-0920

IS - 2

ER -