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

E. Tagliabue; Maria Concetta Fargnoli; Sara Gandini; Patrick Maisonneuve; F. Liu; M. Kayser; T. Nijsten; J. Han; R. Kumar; N. A. Gruis; L. Ferrucci; W. Branicki; Terence Dwyer; L. Blizzard; P. Helsing; P. Autier; J. C. García-Borrón; P. A. Kanetsky; M. T. Landi; Julian Little; Julia Newton-Bishop; Francesco Sera; S. Raimondi; Saverio Caini; Albert Hofman; Andre G. Uitterlinden; Dominique Scherer; Eduardo Nagore; Johan Hansson; Veronica Hoiom; Paola Ghiorzo; Lorenza Pastorino; Jan Nico Bouwes Bavinck; Paula Aguilera; Celia Badenas; Cristina Carrera; Josep Malvehy; Miriam Potrony Mateu; Susana Puig; Joan Anton Puig-Butille; Gemma Tell; Jennifer Cochrane; Ricardo Fernandez-De-Misa; Tadeusz Debniak; Niels Morling; Peter Johansen; Susan Mayne; Allen Bale; Brenda Cartmel; Ruth Pfeiffer; Giuseppe Palmieri; Gloria Ribas; Alexander Stratigos; Katerina Kypreou; Anne Bowcock; Lynn Cornelius; M. Laurin Council; Tomonori Motokawa; Sumiko Anno; 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

doi:10.1038/bjc.2015.231

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

E. Tagliabue, Maria Concetta Fargnoli, Sara Gandini, Patrick Maisonneuve, F. Liu, M. Kayser, T. Nijsten, J. Han, R. Kumar, N. A. Gruis, L. Ferrucci, W. Branicki, Terence Dwyer, L. Blizzard, P. Helsing, P. Autier, J. C. García-Borrón, P. A. Kanetsky, M. T. Landi, Julian LittleJulia Newton-Bishop, Francesco Sera, S. Raimondi, Saverio Caini, Albert Hofman, Andre G. Uitterlinden, Dominique Scherer, Eduardo Nagore, Johan Hansson, Veronica Hoiom, Paola Ghiorzo, Lorenza Pastorino, Jan Nico Bouwes Bavinck, Paula Aguilera, Celia Badenas, Cristina Carrera, Josep Malvehy, Miriam Potrony Mateu, Susana Puig, Joan Anton Puig-Butille, Gemma Tell, Jennifer Cochrane, Ricardo Fernandez-De-Misa, Tadeusz Debniak, Niels Morling, Peter Johansen, Susan Mayne, Allen Bale, Brenda Cartmel, Ruth Pfeiffer, Giuseppe Palmieri, Gloria Ribas, Alexander Stratigos, Katerina Kypreou, Anne Bowcock, Lynn Cornelius, M. Laurin Council, Tomonori Motokawa, Sumiko Anno, 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

Cancer Center

Research output: Contribution to journal › Article › peer-review

48 Scopus citations

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 language	English (US)
Pages (from-to)	354-363
Number of pages	10
Journal	British journal of cancer
Volume	113
Issue number	2
DOIs	https://doi.org/10.1038/bjc.2015.231
State	Published - Jul 14 2015

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1038/bjc.2015.231

Cite this

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., ... 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

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, Caini, S, Hofman, A, Uitterlinden, AG, Scherer, D, Nagore, E, Hansson, J, Hoiom, V, Ghiorzo, P, Pastorino, L, Bavinck, JNB, Aguilera, P, Badenas, C, Carrera, C, Malvehy, J, Mateu, MP, Puig, S, Puig-Butille, JA, Tell, G, Cochrane, J, Fernandez-De-Misa, R, Debniak, T, Morling, N, Johansen, P, Mayne, S, Bale, A, Cartmel, B, Pfeiffer, R, Palmieri, G, Ribas, G, Stratigos, A, Kypreou, K, Bowcock, A, Cornelius, L, Council, ML, Motokawa, T, Anno, S, 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

@article{a72eab5675654ee7a5b339f1eba0e26d,

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, {Maria Concetta} and Sara Gandini and Patrick 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 Terence 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 Julian Little and Julia Newton-Bishop and Francesco Sera and S. Raimondi and Saverio Caini and Albert Hofman and Uitterlinden, {Andre G.} and Dominique Scherer and Eduardo Nagore and Johan Hansson and Veronica Hoiom and Paola Ghiorzo and Lorenza Pastorino 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 Jennifer Cochrane and Ricardo Fernandez-De-Misa and Tadeusz Debniak and Niels Morling and Peter Johansen and Susan Mayne and Allen Bale and Brenda Cartmel and Ruth Pfeiffer and Giuseppe Palmieri 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 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",

note = "Funding Information: This work was supported by the Italian Association for Cancer Research (grant number: MFAG 11831). The M-SKIP study group consists of the following members: Principal Investigator: Sara Raimondi (the European Institute of Oncology, Milan, Italy); Advisory Committee members: Philippe Autier (the International Prevention Research Institute, Lyon, France), Maria Concetta Fargnoli (the University of L{\textquoteright}Aquila, Italy), Jos{\'e} C Garc{\'i}a-Borr{\'o}n (the University of Murcia, Spain), Jiali Han (Brigham and Women{\textquoteright}s Hospital and Harvard Medical School, Boston, MA, USA), Peter A Kanetsky (Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA), Maria Teresa Landi (the National Cancer Institute, NIH, Bethesda, MD, USA), Julian Little (the University of Ottawa, Canada), Julia Newton-Bishop (the University of Leeds, UK), Francesco Sera (the UCL Institute of Child Health, London, UK); Consultants: Saverio Caini (ISPO, Florence, Italy), Sara Gandini and Patrick Maisonneuve (the European Institute of Oncology, Milan, Italy); Participant Investigators: Albert Hofman, Manfred Kayser, Fan Liu, Tamar Nijsten and Andre G. Uitterlinden (the Erasmus MC University Medical Center, Rotterdam, The Netherlands), Rajiv Kumar and Dominique Scherer (the German Cancer Research Center, Heidelberg, Germany), Eduardo Nagore (the Instituto Valenciano de Oncologia, Valencia, Spain), Johan Hansson and Veronica Hoiom (Karolinska Institutet, Stockholm, Sweden), Paola Ghiorzo and Lorenza Pastorino (the University of Genoa, Italy), Nelleke A. Gruis and Jan Nico Bouwes Bavinck (the Leiden University Medical Center, The Netherlands), Paula Aguilera, Celia Badenas, Cristina Carrera, Josep Malvehy, Miriam Potrony Mateu, Susana Puig, Joan Anton Puig-Butille, Gemma Tell (the Hospital Clinic, IDIBAPS and CIBERER, Barcelona, Spain), Terence Dwyer (the Murdoch Childrens Research Institute, Victoria, Australia), Leigh Blizzard and Jennifer Cochrane (the Menzies Research Institute Tasmania, Hobart, Australia), Ricardo Fernandez-de-Misa (the Hospital Universitario Nuestra Se{\~n}ora de Candelaria, Santa Cruz de Tenerife, Spain), Wojciech Branicki (the Institute of Forensic Research, Krakow, Poland), Tadeusz Debniak (the Pomeranian Medical University, Polabska, Poland), Niels Morling and Peter Johansen (the University of Copenhagen, Denmark), Susan Mayne, Allen Bale, Brenda Cartmel and Leah Ferrucci (the Yale School of Public Health and Medicine, New Haven, CT, USA), Ruth Pfeiffer (the National Cancer Institute, NIH, Bethesda, MD, USA), Giuseppe Palmieri (the Istituto di Chimica Biomolecolare, CNR, Sassari, Italy), Gloria Ribas (the Fundaci{\'o}n Investigaci{\'o}n Cl{\'i}nico de Valencia Instituto de Investigaci{\'o}n Sanitaria-INCLIVA, Spain), Alexander Stratigos and Katerina Kypreou (the University of Athens, Andreas Sygros Hospital, Athens, Greece), Anne Bowcock, Lynn Cornelius and M. Laurin Council (the Washington University School of Medicine, St Louis, MO, USA), Tomonori Motokawa (POLA Chemical Industries, Yokohama, Japan), Sumiko Anno (the Shibaura Institute of Technology, Tokyo, Japan), Per Helsing and Per Arne Andresen (the Oslo University Hospital, Norway), Terence H. Wong (the University of Edinburgh, UK) and the GEM Study Group. Participants in the GEM Study Group are as follows: Coordinating Center, Memorial Sloan-Kettering Cancer Center, New York, NY, USA: Marianne Berwick (PI, currently at the University of New Mexico), Colin Begg (Co-PI), Irene Orlow (Co-Investigator), Urvi Mujumdar (Project Coordinator), Amanda Hummer (Biostatistician), Klaus Busam (Dermatopathologist), Pampa Roy (Laboratory Technician), Rebecca Canchola (Laboratory Technician), Brian Clas (Laboratory Technician), Javiar Cotignola (Laboratory Technician), Yvette Monroe (Interviewer). Study Centers: The University of Sydney and The Cancer Council New South Wales, Sydney (Australia): Bruce Armstrong (PI), Anne Kricker (co-PI), Melisa Litchfield (Study Coordinator). Menzies Centre for Population Health Research, the University of Tasmania, Hobart (Australia): Terence Dwyer (PI), Paul Tucker (Dermatopathologist), Nicola Stephens (Study Coordinator). The British Columbia Cancer Agency, Vancouver (Canada): Richard Gallagher (PI), Teresa Switzer (Coordinator). The Cancer Care Ontario, Toronto (Canada): Loraine Marrett (PI), Beth Theis (Co-Investigator), Lynn From (Dermatopathologist), Noori Chowdhury (Coordinator), Louise Vanasse (Coordinator), Mark Purdue (Research Officer). David Northrup (Manager for CATI). Centro per la Prevenzione Oncologia Torino, Piemonte (Italy): Roberto Zanetti (PI), Stefano Rosso (Data Manager), Carlotta Sacerdote (Coordinator). The University of California, Irvine (USA): Hoda Anton-Culver (PI), Nancy Leighton (Coordinator), Maureen Gildea (Data Manager). The University of Michigan, Ann Arbor (USA): Stephen Gruber (PI), Joe Bonner (Data Manager), Joanne Jeter (Coordinator). The New Jersey Department of Health and Senior Services, Trenton (USA): Judith Klotz (PI), Homer Wilcox (Co-PI), Helen Weiss (Coordinator). The University of North Carolina, Chapel Hill (USA): Robert Millikan (PI), Nancy Thomas (Co-Investigator), Dianne Mattingly (Coordinator), Jon Player (Laboratory Technician), Chiu-Kit Tse (Data Analyst). The University of Pennsylvania, Philadelphia, PA (USA): Timothy Rebbeck (PI), Peter Kanetsky (Co-Investigator), Amy Walker (Laboratory Technician), Saarene Panossian (Laboratory Technician). Consultants: Harvey Mohrenweiser, The University of California, Irvine, Irvine, CA (USA); Richard Setlow, The Brookhaven National Laboratory, Upton, NY (USA).",

year = "2015",

month = jul,

day = "14",

doi = "10.1038/bjc.2015.231",

language = "English (US)",

volume = "113",

pages = "354--363",

journal = "British journal of cancer",

issn = "0007-0920",

publisher = "Springer Nature",

number = "2",

}

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, Maria Concetta

AU - Gandini, Sara

AU - Maisonneuve, Patrick

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, Terence

AU - Blizzard, L.

AU - Helsing, P.

AU - Autier, P.

AU - García-Borrón, J. C.

AU - Kanetsky, P. A.

AU - Landi, M. T.

AU - Little, Julian

AU - Newton-Bishop, Julia

AU - Sera, Francesco

AU - Raimondi, S.

AU - Caini, Saverio

AU - Hofman, Albert

AU - Uitterlinden, Andre G.

AU - Scherer, Dominique

AU - Nagore, Eduardo

AU - Hansson, Johan

AU - Hoiom, Veronica

AU - Ghiorzo, Paola

AU - Pastorino, Lorenza

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 - Cochrane, Jennifer

AU - Fernandez-De-Misa, Ricardo

AU - Debniak, Tadeusz

AU - Morling, Niels

AU - Johansen, Peter

AU - Mayne, Susan

AU - Bale, Allen

AU - Cartmel, Brenda

AU - Pfeiffer, Ruth

AU - Palmieri, Giuseppe

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 - 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

N1 - Funding Information: This work was supported by the Italian Association for Cancer Research (grant number: MFAG 11831). The M-SKIP study group consists of the following members: Principal Investigator: Sara Raimondi (the European Institute of Oncology, Milan, Italy); Advisory Committee members: Philippe Autier (the International Prevention Research Institute, Lyon, France), Maria Concetta Fargnoli (the University of L’Aquila, Italy), José C García-Borrón (the University of Murcia, Spain), Jiali Han (Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA), Peter A Kanetsky (Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA), Maria Teresa Landi (the National Cancer Institute, NIH, Bethesda, MD, USA), Julian Little (the University of Ottawa, Canada), Julia Newton-Bishop (the University of Leeds, UK), Francesco Sera (the UCL Institute of Child Health, London, UK); Consultants: Saverio Caini (ISPO, Florence, Italy), Sara Gandini and Patrick Maisonneuve (the European Institute of Oncology, Milan, Italy); Participant Investigators: Albert Hofman, Manfred Kayser, Fan Liu, Tamar Nijsten and Andre G. Uitterlinden (the Erasmus MC University Medical Center, Rotterdam, The Netherlands), Rajiv Kumar and Dominique Scherer (the German Cancer Research Center, Heidelberg, Germany), Eduardo Nagore (the Instituto Valenciano de Oncologia, Valencia, Spain), Johan Hansson and Veronica Hoiom (Karolinska Institutet, Stockholm, Sweden), Paola Ghiorzo and Lorenza Pastorino (the University of Genoa, Italy), Nelleke A. Gruis and Jan Nico Bouwes Bavinck (the Leiden University Medical Center, The Netherlands), Paula Aguilera, Celia Badenas, Cristina Carrera, Josep Malvehy, Miriam Potrony Mateu, Susana Puig, Joan Anton Puig-Butille, Gemma Tell (the Hospital Clinic, IDIBAPS and CIBERER, Barcelona, Spain), Terence Dwyer (the Murdoch Childrens Research Institute, Victoria, Australia), Leigh Blizzard and Jennifer Cochrane (the Menzies Research Institute Tasmania, Hobart, Australia), Ricardo Fernandez-de-Misa (the Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain), Wojciech Branicki (the Institute of Forensic Research, Krakow, Poland), Tadeusz Debniak (the Pomeranian Medical University, Polabska, Poland), Niels Morling and Peter Johansen (the University of Copenhagen, Denmark), Susan Mayne, Allen Bale, Brenda Cartmel and Leah Ferrucci (the Yale School of Public Health and Medicine, New Haven, CT, USA), Ruth Pfeiffer (the National Cancer Institute, NIH, Bethesda, MD, USA), Giuseppe Palmieri (the Istituto di Chimica Biomolecolare, CNR, Sassari, Italy), Gloria Ribas (the Fundación Investigación Clínico de Valencia Instituto de Investigación Sanitaria-INCLIVA, Spain), Alexander Stratigos and Katerina Kypreou (the University of Athens, Andreas Sygros Hospital, Athens, Greece), Anne Bowcock, Lynn Cornelius and M. Laurin Council (the Washington University School of Medicine, St Louis, MO, USA), Tomonori Motokawa (POLA Chemical Industries, Yokohama, Japan), Sumiko Anno (the Shibaura Institute of Technology, Tokyo, Japan), Per Helsing and Per Arne Andresen (the Oslo University Hospital, Norway), Terence H. Wong (the University of Edinburgh, UK) and the GEM Study Group. Participants in the GEM Study Group are as follows: Coordinating Center, Memorial Sloan-Kettering Cancer Center, New York, NY, USA: Marianne Berwick (PI, currently at the University of New Mexico), Colin Begg (Co-PI), Irene Orlow (Co-Investigator), Urvi Mujumdar (Project Coordinator), Amanda Hummer (Biostatistician), Klaus Busam (Dermatopathologist), Pampa Roy (Laboratory Technician), Rebecca Canchola (Laboratory Technician), Brian Clas (Laboratory Technician), Javiar Cotignola (Laboratory Technician), Yvette Monroe (Interviewer). Study Centers: The University of Sydney and The Cancer Council New South Wales, Sydney (Australia): Bruce Armstrong (PI), Anne Kricker (co-PI), Melisa Litchfield (Study Coordinator). Menzies Centre for Population Health Research, the University of Tasmania, Hobart (Australia): Terence Dwyer (PI), Paul Tucker (Dermatopathologist), Nicola Stephens (Study Coordinator). The British Columbia Cancer Agency, Vancouver (Canada): Richard Gallagher (PI), Teresa Switzer (Coordinator). The Cancer Care Ontario, Toronto (Canada): Loraine Marrett (PI), Beth Theis (Co-Investigator), Lynn From (Dermatopathologist), Noori Chowdhury (Coordinator), Louise Vanasse (Coordinator), Mark Purdue (Research Officer). David Northrup (Manager for CATI). Centro per la Prevenzione Oncologia Torino, Piemonte (Italy): Roberto Zanetti (PI), Stefano Rosso (Data Manager), Carlotta Sacerdote (Coordinator). The University of California, Irvine (USA): Hoda Anton-Culver (PI), Nancy Leighton (Coordinator), Maureen Gildea (Data Manager). The University of Michigan, Ann Arbor (USA): Stephen Gruber (PI), Joe Bonner (Data Manager), Joanne Jeter (Coordinator). The New Jersey Department of Health and Senior Services, Trenton (USA): Judith Klotz (PI), Homer Wilcox (Co-PI), Helen Weiss (Coordinator). The University of North Carolina, Chapel Hill (USA): Robert Millikan (PI), Nancy Thomas (Co-Investigator), Dianne Mattingly (Coordinator), Jon Player (Laboratory Technician), Chiu-Kit Tse (Data Analyst). The University of Pennsylvania, Philadelphia, PA (USA): Timothy Rebbeck (PI), Peter Kanetsky (Co-Investigator), Amy Walker (Laboratory Technician), Saarene Panossian (Laboratory Technician). Consultants: Harvey Mohrenweiser, The University of California, Irvine, Irvine, CA (USA); Richard Setlow, The Brookhaven National Laboratory, Upton, NY (USA).

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.

UR - http://www.scopus.com/inward/record.url?scp=84937073564&partnerID=8YFLogxK

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U2 - 10.1038/bjc.2015.231

DO - 10.1038/bjc.2015.231

M3 - Article

C2 - 26103569

AN - SCOPUS:84937073564

SN - 0007-0920

VL - 113

SP - 354

EP - 363

JO - British journal of cancer

JF - British journal of cancer

IS - 2

ER -

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

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