Epidemiology of MelanomaMC1R variants and cutaneous melanoma risk according to histological type, body site, and Breslow thickness: a pooled analysis from the M-SKIP projectCaini, Saverioa; Gandini, Sarab; Botta, Francescac,,d; Tagliabue, Elenae; Raimondi, Sarab; Nagore, Eduardof; Zanna, Inesa; Maisonneuve, Patrickd; Newton-Bishop, Juliag; Polsky, Davidh; Lazovich, DeAnni; Kumar, Rajivj; Kanetsky, Peter A.k; Hoiom, Veronical; Ghiorzo, Paolam; Landi, Maria Teresan; Ribas, Gloriao; Menin, Chiarap; Stratigos, Alexander J.q; Palmieri, Giusepper; Guida, Gabriellas; García-Borrón, Jose Carlost; Nan, Hongmeiu; Little, Julianv; Sera, Francescow; Puig, Susanax; Fargnoli, Maria Concettay,,z; on behalf of the M-SKIP study groupAuthor Information aCancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence bMolecular and Pharmaco-Epidemiology Unit, Department of Molecular Oncology, IEO, European Institute of Oncology IRCCS cDepartment of Statistics and Quantitative Methods, Università degli Studi di Milano-Bicocca dDivision of Epidemiology and Biostatistics, IEO, European Institute of Oncology IRCCS eIRCCS MultiMedica, Milan, Italy fDepartment of Dermatology, Instituto Valenciano de Oncologia, Valencia, Spain gSection of Epidemiology and Biostatistics, Institute of Medical Research at St James’s, University of Leeds, Leeds, UK hThe Ronald O. Perelman Department of Dermatology, New York University School of Medicine, NYU Langone Medical Center, New York, New York iDivision of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota, USA jDivision of Molecular Genetic Epidemiology, German Cancer Research Center, Heidelberg, Germany kDepartment of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA lDepartment of Oncology and Pathology, Cancer Center, Karolinska Institutet, Stockholm, Sweden mDepartment of Internal Medicine and Medical Specialties, University of Genoa and Ospedale Policlinico San Martino, Genoa, Italy nDivision of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, Maryland, USA oDpdt. Oncologia medica y hematologia, Fundación Investigación Clínico de Valencia Instituto de Investigación Sanitaria- INCLIVA, Valencia, Spain pImmunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology, IOV-IRCCS, Padua, Italy qAndreas Sygros Hospital, National and Kapodistrian University of Athens, Greece rUnit of Cancer Genetics, Istituto di Chimica Biomolecolare, CNR, Sassari sDepartment of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari ‘A. Moro’, Bari, Italy tDepartment of Biochemistry, Molecular Biology and Immunology, University of Murcia and IMIB-Arrixaca, Murcia, Spain uDepartment of Epidemiology, Richard M. Fairbanks School of Public Health, Melvin & Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana, USA vSchool of Epidemiology and Public Health, University of Ottawa, Ottawa, Canada wDepartment of Public Health, Environments and Society, London School of Hygiene & Tropical Medicine, London, UK xMelanoma Unit, Dermatology Department, Hospital Clinic Barcelona, Universitat de Barcelona, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS) Spain & CIBER de Enfermedades Raras, Barcelona, Spain Departments of yDermatology zBiotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy Received 3 January 2020 Accepted 20 March 2020 Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website, www.melanomaresearch.com. Correspondence to Sara Raimondi, PhD, Molecular and Pharmaco-Epidemiology Unit, Department of Experimental Oncology, European Institute of Oncology, Via Ripamonti 435, 20141 Milan, Italy, Tel: +39 0294372711; fax: +39 0257489922; e-mail: firstname.lastname@example.org Melanoma Research: October 2020 - Volume 30 - Issue 5 - p 500-510 doi: 10.1097/CMR.0000000000000668 Buy SDC Metrics Abstract Little is known on whether melanocortin 1 receptor (MC1R) associated cutaneous melanoma (CM) risk varies depending on histological subtype and body site, and whether tumour thickness at diagnosis (the most important prognostic factor for CM patients) differs between MC1R variant carriers and wild-type individuals. We studied the association between MC1R variants and CM risk by histological subtype, body site, and Breslow thickness, using the database of the M-SKIP project. We pooled individual data from 15 case-control studies conducted during 2005–2015 in Europe and the USA. Study-specific, multi-adjusted odds ratios were pooled into summary odds ratios (SOR) and 95% confidence intervals (CI) using random-effects models. Six thousand eight hundred ninety-one CM cases and 5555 controls were included. CM risk was increased among MC1R variant carriers vs. wild-type individuals. The increase in risk was comparable across histological subtypes (SOR for any variant vs. wild-type ranged between 1.57 and 1.70, always statistical significant) except acral lentiginous melanoma (ALM), for which no association emerged; and slightly greater on chronically (1.74, 95% CI 1.47–2.07) than intermittently (1.55, 95% CI 1.34–1.78) sun-exposed skin. CM risk was greater for those carrying ‘R’ vs. ‘r’ variants; correlated with the number of variants; and was more evident among individuals not showing the red hair colour phenotype. Breslow thickness was not associated with MC1R status. MC1R variants were associated with an increased risk of CM of any histological subtype (except ALM) and occurring on both chronically and intermittently sun-exposed skin. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.