. 2015 Jul 14;113(2):354-63.

doi: 10.1038/bjc.2015.231. Epub 2015 Jun 23.

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

E Tagliabue¹, M C Fargnoli², S Gandini¹, P Maisonneuve¹, F Liu³, M Kayser³, T Nijsten⁴, J Han⁵, R Kumar⁶, N A Gruis⁷, L Ferrucci⁸, W Branicki⁹, T Dwyer¹⁰, L Blizzard¹¹, P Helsing¹², P Autier¹³, J C García-Borrón¹⁴, P A Kanetsky¹⁵, M T Landi¹⁶, J Little¹⁷, J Newton-Bishop¹⁸, F Sera¹⁹, S Raimondi¹; M-SKIP Study Group

Collaborators, Affiliations

Collaborators

M-SKIP Study Group:
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, 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, Giuseppe Palmieri, Chimica Biomolecolare, Gloria Ribas, Alexander Stratigos, Katerina Kypreou, Andreas Sygros, Anne Bowcock, Lynn Cornelius, M Laurin Council, Tomonori Motokawa, Sumiko Anno, Per Helsing, Per Arne Andresen, Terence H Wong, Marianne Berwick, Colin Begg, Irene Orlow, Amanda Hummer, Klaus Busam, Pampa Roy, Rebecca Canchola, Brian Clas, Javiar Cotignola, Yvette Monroe, Bruce Armstrong, Anne Kricker, Melisa Litchfield, Terence Dwyer, Paul Tucker, Nicola Stephens, Richard Gallagher, Teresa Switzer, Loraine Marrett, Beth Theis, Noori Chowdhury, Louise Vanasse, Mark Purdue, David Northrup, Roberto Zanetti, Stefano Rosso, 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 Kanetsky, Amy Walker, Saarene Panossian, Harvey Mohrenweiser, Richard Setlow

Affiliations

¹ Division of Epidemiology and Biostatistics, European Institute of Oncology, Via Ripamonti 435, Milan 20141, Italy.
² Department of Dermatology, University of L'Aquila, 47100 L'Aquila, Italy.
³ Department of Forensic Molecular Biology, Erasmus MC University Medical Center, 3000 DR Rotterdam, The Netherlands.
⁴ Department of Dermatology, Erasmus MC University Medical Center, 3000 DR Rotterdam, The Netherlands.
⁵ 1] Department of Dermatology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA [2] Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA [3] Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
⁶ Division of Molecular Genetic Epidemiology, German Cancer Research Center, D-69120 Heidelberg, Germany.
⁷ Department of Dermatology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
⁸ Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale Cancer Center, New Haven, CT 06520-8034, USA.
⁹ Institute of Forensic Research, 31-033 Krakow, Poland.
¹⁰ Murdoch Childrens Research Institute, Royal Children's Hospital, Victoria 3052, Australia.
¹¹ Menzies Research Institute Tasmania, University of Tasmania, Hobart, 7001 Australia.
¹² Department of Pathology, Oslo University Hospital, N-0027 Oslo, Norway.
¹³ International Prevention Research Institute, Lyon 69006, France.
¹⁴ Department of Biochemistry, Molecular Biology and Immunology, University of Murcia, 30100 Murcia, Spain.
¹⁵ Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL 33612, USA.
¹⁶ Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892-7236, USA.
¹⁷ School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Canada ON K1N 6N5.
¹⁸ Section of Epidemiology and Biostatistics, Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, UK.
¹⁹ UCL Institute of Child Health, London WC1N 1EH, UK.

PMID: 26103569
PMCID: PMC4506395
DOI: 10.1038/bjc.2015.231

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

E Tagliabue et al. Br J Cancer. 2015.

. 2015 Jul 14;113(2):354-63.

doi: 10.1038/bjc.2015.231. Epub 2015 Jun 23.

Authors

Collaborators

M-SKIP Study Group:
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, 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, Giuseppe Palmieri, Chimica Biomolecolare, Gloria Ribas, Alexander Stratigos, Katerina Kypreou, Andreas Sygros, Anne Bowcock, Lynn Cornelius, M Laurin Council, Tomonori Motokawa, Sumiko Anno, Per Helsing, Per Arne Andresen, Terence H Wong, Marianne Berwick, Colin Begg, Irene Orlow, Amanda Hummer, Klaus Busam, Pampa Roy, Rebecca Canchola, Brian Clas, Javiar Cotignola, Yvette Monroe, Bruce Armstrong, Anne Kricker, Melisa Litchfield, Terence Dwyer, Paul Tucker, Nicola Stephens, Richard Gallagher, Teresa Switzer, Loraine Marrett, Beth Theis, Noori Chowdhury, Louise Vanasse, Mark Purdue, David Northrup, Roberto Zanetti, Stefano Rosso, 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 Kanetsky, Amy Walker, Saarene Panossian, Harvey Mohrenweiser, Richard Setlow

Affiliations

¹ Division of Epidemiology and Biostatistics, European Institute of Oncology, Via Ripamonti 435, Milan 20141, Italy.
² Department of Dermatology, University of L'Aquila, 47100 L'Aquila, Italy.
³ Department of Forensic Molecular Biology, Erasmus MC University Medical Center, 3000 DR Rotterdam, The Netherlands.
⁴ Department of Dermatology, Erasmus MC University Medical Center, 3000 DR Rotterdam, The Netherlands.
⁵ 1] Department of Dermatology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA [2] Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA [3] Department of Epidemiology, Harvard School of Public Health, Boston, MA 02115, USA.
⁶ Division of Molecular Genetic Epidemiology, German Cancer Research Center, D-69120 Heidelberg, Germany.
⁷ Department of Dermatology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
⁸ Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale Cancer Center, New Haven, CT 06520-8034, USA.
⁹ Institute of Forensic Research, 31-033 Krakow, Poland.
¹⁰ Murdoch Childrens Research Institute, Royal Children's Hospital, Victoria 3052, Australia.
¹¹ Menzies Research Institute Tasmania, University of Tasmania, Hobart, 7001 Australia.
¹² Department of Pathology, Oslo University Hospital, N-0027 Oslo, Norway.
¹³ International Prevention Research Institute, Lyon 69006, France.
¹⁴ Department of Biochemistry, Molecular Biology and Immunology, University of Murcia, 30100 Murcia, Spain.
¹⁵ Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL 33612, USA.
¹⁶ Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892-7236, USA.
¹⁷ School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, Canada ON K1N 6N5.
¹⁸ Section of Epidemiology and Biostatistics, Institute of Cancer and Pathology, University of Leeds, Leeds LS9 7TF, UK.
¹⁹ UCL Institute of Child Health, London WC1N 1EH, UK.

PMID: 26103569
PMCID: PMC4506395
DOI: 10.1038/bjc.2015.231

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.

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Figures

**Figure 1**
**Attributable risks^a with 95% confidence intervals in the population for non-melanoma skin cancer according to different *MC1R* variants^b (percentages).** Black bars represent BCC, white bars represent SCC. ^aMiettinen's formula (OR−1/OR × proportion cases exposed). ^bOnly variants significantly associated with BCC and/or SCC are represented.

See this image and copyright information in PMC

References

1. American Cancer Society 2012. Skin cancer: Basal and Squamous CellAmerican Cancer Society; Available from http://www.cancer.org/cancer/skincancer-basalandsquamouscell/detailedgui... .
1. Andresen PA, Nymoen DA, Kjaerheim K, Leivestad T, Helsing P. Susceptibility to cutaneous squamous cell carcinoma in renal transplant recipients associates with genes regulating melanogenesis independent of their role in pigmentation. Biomark Cancer. 2013;5:41–47. - PMC - PubMed
1. April CS, Barsh GS. Distinct pigmentary and melanocortin 1 receptor-dependent components of cutaneous defense against ultraviolet radiation. PLoS Genet. 2007;3:e9. - PMC - PubMed
1. Bastiaens MT, ter Huurne JA, Kielich C, Gruis NA, Westendorp RG, Vermeer BJ, Bavinck JN, Leiden Skin Cancer Study Team Melanocortin-1 receptor gene variants determine the risk of nonmelanoma skin cancer independently of fair skin and red hair. Am J Hum Genet. 2001;68:884–894. - PMC - PubMed
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MC1R gene variants and non-melanoma skin cancer: a pooled-analysis from the M-SKIP project

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Molecular Biology Databases

Research Materials