Assessment of tyrosinase variants and skin cancer risk in a large cohort of French subjects

作者：Hu Hui Han; Guedj Mickael; Descamps Vincent; Jouary Thomas; Bourillon Agnes; Ezzedine Khaled; Taieb Alain; Bagot Martine; Bensussan Armand; Saiag Philippe; Grandchamp Bernard; Basset Seguin Nicole; Soufir Nadem^*

来源：Journal of Dermatological Science, 2011, 64(2): 127-133.

DOI：10.1016/j.jdermsci.2011.07.003

• Tyrosinase
• Polymorphisms
• Melanoma
• Basal cell carcinoma
• Albinism

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.
Conclusion: 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 SIC These results should be confirmed by replications studies.

• 出版日期2011-11