MC1R variants and cutaneous melanoma risk according to histological type, body site, and Breslow thickness: A pooled analysis from the M-SKIP project

Saverio Caini, Sara Gandini, Francesca Botta, Elena Tagliabue, Sara Raimondi, Eduardo Nagore, Ines Zanna, Patrick Maisonneuve, Julia Newton-Bishop, David Polsky, De Ann Lazovich, Rajiv Kumar, Peter A. Kanetsky, Veronica Hoiom, Paola Ghiorzo, Maria Teresa Landi, Gloria Ribas, Chiara Menin, Alexander J. Stratigos, Giuseppe PalmieriGabriella Guida, Jose Carlos García-Borrón, Hongmei Nan, Julian Little, Francesco Sera, Susana Puig, Maria Concetta Fargnoli

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)500-510
Number of pages11
JournalMelanoma Research
DOIs
Publication statusAccepted/In press - 2020

Keywords

  • body site
  • Breslow thickness
  • cutaneous melanoma
  • histological subtype
  • melanocortin 1 receptor
  • pooled analysis

ASJC Scopus subject areas

  • Oncology
  • Dermatology
  • Cancer Research

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