1. Melanoma risk associated with MC1R gene variants in Latvia and the functional analysis of rare variants
- Author
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Guna Proboka, Simona Doniņa, Ludmila Eņģele, Olita Heisele, Kristīne Azarjana, Baiba Streinerte, Dace Pjanova, Ilona Mandrika, Ingrīda Čēma, Ramona Petrovska, and Aija Ozola
- Subjects
Adult ,Male ,Cancer Research ,Skin Neoplasms ,Genotype ,Green Fluorescent Proteins ,Population ,Mutation, Missense ,Biology ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,Cell Line ,Gene Frequency ,Risk Factors ,Cyclic AMP ,Genetics ,medicine ,Genetic predisposition ,Animals ,Humans ,Genetic Predisposition to Disease ,education ,Melanoma ,Molecular Biology ,Gene ,Aged ,Aged, 80 and over ,education.field_of_study ,Microscopy, Confocal ,Cell Membrane ,Odds ratio ,Middle Aged ,medicine.disease ,Latvia ,Phenotype ,Confidence interval ,Female ,Receptor, Melanocortin, Type 1 ,Melanocortin 1 receptor - Abstract
To evaluate the association ofmelanocortin 1 receptorgene (MC1R) variants withmelanomarisk in a Latvian population, theMC1Rgene was sequenced in 200 melanoma patients and 200 control persons. A functional study of previously uncharacterized, rareMC1Rvariants was also performed. In total, 26 differentMC1Rvariants, including two novel variants Val165Ile and Val188Ile, were detected. The highest risk of melanoma was associated with the Arg151Cys variant (odds ratio (OR) 4.47, 95% confidence interval (CI) 2.19–9.14,P< 0.001). Agene dosageeffect was observed, with melanoma risk for carriers of two variants being twice (OR3.98, 95% CI2.15–7.38,P< 0.001) that of carriers of one variant (OR 1.98, 95% CI 1.26–3.11,P= 0.003). After stratification according to thepigmentationphenotype, the risk of melanoma remained in groups with otherwise protective phenotypes. Functional analyses of eight previously uncharacterizedMC1Rvariants revealed that a subset of them is functionally relevant. Our resultssupport the contribution ofMC1Rvariants to agenetic predispositionto melanoma in Latvia.
- Published
- 2013
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