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 | |
State | Published - Jul 14 2015 |
ASJC Scopus subject areas
- Oncology
- Cancer Research
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MC1R gene variants and non-melanoma skin cancer : A pooled-analysis from the M-SKIP project. / Tagliabue, E.; Fargnoli, Maria Concetta; Gandini, Sara et al.
In: British journal of cancer, Vol. 113, No. 2, 14.07.2015, p. 354-363.Research output: Contribution to journal › Article › peer-review
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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, 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
UR - http://www.scopus.com/inward/citedby.url?scp=84937073564&partnerID=8YFLogxK
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 -