title: Assessment of tyrosinase variants and skin cancer risk in a large cohort of French subjects.
abstract: BACKGROUND
  Tyrosinase (TYR) is a key pigmentation gene that is highly polymorphic and responsible for the most common form of autosomal recessive albinism, OCA1.
  
  
  OBJECTIVE
  To assess the role of frequent and rare TYR variants in predisposition to skin cancer (SK) in the French population.
  
  
  METHODS
  We genotyped a frequent TYR variant (p.R402Q) in 1273 patients {1047 cutaneous melanoma (CM) and 226 basal cell carcinoma (BCC)} and 925 controls, and the full coding region of TYR was sequenced in 287 patients suspected of genetic predisposition to SK (familial and/or multiple SK and/or onset before 40 years) and 187 controls.
  
  
  RESULTS
  The homozygous p.R402Q variant was significantly associated with SK risk (P value=0.008; OR=1.57), and was mostly associated with multiple CM risk (P value=0.021; OR=2.50) and familial CM risk (P value=0.022; OR=2.16). In addition, 19 rare TYR variants, mainly albinism mutations, were identified in 15 patients and 8 controls. Among these, 3 clearly deleterious mutations (1 non-sense and 2 affecting mRNA splicing) were identified in 3 patients, one of which was homozygous.
  
  
  CONCLUSIONS
  Our data confirmed the association of TYR p.R402Q with SK risk in the French population, and support that rare deleterious TYR variants may also play a role in multi-factorial genetic predisposition to SK. These results should be confirmed by replications studies.
authors: Laboratoire de Biochimie Hormonale et Génétique, Hôpital Bichat Claude Bernard, APHP, IFR02, 75018, Paris, France.
authors: Hui-Han
authors: HH
authors: Hu
authors: Mickael
authors: M
authors: Guedj
authors: Vincent
authors: V
authors: Descamps
authors: Thomas
authors: T
authors: Jouary
authors: Agnes
authors: A
authors: Bourillon
authors: Khaled
authors: K
authors: Ezzedine
authors: Alain
authors: A
authors: Taieb
authors: Martine
authors: M
authors: Bagot
authors: Armand
authors: A
authors: Bensussan
authors: Philippe
authors: P
authors: Saiag
authors: Bernard
authors: B
authors: Grandchamp
authors: Nicole
authors: N
authors: Basset-Seguin
authors: Nadem
authors: N
authors: Soufir
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D015331:Cohort Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008545:Melanoma / Q000209:etiology / Q000235:genetics; D008875:Middle Aged; D014442:Monophenol Monooxygenase / Q000235:genetics*; D015999:Multivariate Analysis; D012306:Risk; D012878:Skin Neoplasms / Q000209:etiology / Q000235:genetics*; D012880:Skin Pigmentation
chemical_list: D014442:Monophenol Monooxygenase