TY - JOUR
T1 - Melanoma risk associated with MC1R gene variants in Latvia and the functional analysis of rare variants
AU - Ozola, Aija
AU - Azarjana, Kristīne
AU - Doniņa, Simona
AU - Proboka, Guna
AU - Mandrika, Ilona
AU - Petrovska, Ramona
AU - Čēma, Ingrīda
AU - Heisele, Olita
AU - Eņģele, Ludmila
AU - Štreinerte, Baiba
AU - Pjanova, Dace
N1 - Funding Information:
This work was supported by the grant of European Economic Area (EEA) Nr. EEZ09AP-38/08 and the European Regional Development Fund (ERDF) project No. 2010/0233/2DP/2.1.1.1.0/10/APIA/VIAA/076. We acknowledge Genome Database of Latvian Population, Latvian Biomedical Research and Study Center for providing DNA samples. We thank Davids Fridmanis for assistance with the statistical analysis, Alexander Rivosh for assistance with the pictures, and Anna Azarjana for language editing.
PY - 2013/3
Y1 - 2013/3
N2 - To evaluate the association of melanocortin 1 receptor gene (. MC1R) variants with melanoma risk in a Latvian population, the MC1R gene was sequenced in 200 melanoma patients and 200 control persons. A functional study of previously uncharacterized, rare MC1R variants was also performed. In total, 26 different MC1R variants, 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). A gene dosage effect was observed, with melanoma risk for carriers of two variants being twice (OR 3.98, 95% CI 2.15-7.38, 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 the pigmentation phenotype, the risk of melanoma remained in groups with otherwise protective phenotypes. Functional analyses of eight previously uncharacterized MC1R variants revealed that a subset of them is functionally relevant. Our results support the contribution of MC1R variants to a genetic predisposition to melanoma in Latvia.
AB - To evaluate the association of melanocortin 1 receptor gene (. MC1R) variants with melanoma risk in a Latvian population, the MC1R gene was sequenced in 200 melanoma patients and 200 control persons. A functional study of previously uncharacterized, rare MC1R variants was also performed. In total, 26 different MC1R variants, 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). A gene dosage effect was observed, with melanoma risk for carriers of two variants being twice (OR 3.98, 95% CI 2.15-7.38, 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 the pigmentation phenotype, the risk of melanoma remained in groups with otherwise protective phenotypes. Functional analyses of eight previously uncharacterized MC1R variants revealed that a subset of them is functionally relevant. Our results support the contribution of MC1R variants to a genetic predisposition to melanoma in Latvia.
KW - Functionality of MC1R variants
KW - Melanocortin 1 receptor gene
KW - Melanoma
KW - Pigmentation
KW - Rare MC1R variants
UR - http://www.scopus.com/inward/record.url?scp=84875919837&partnerID=8YFLogxK
U2 - 10.1016/j.cancergen.2013.01.002
DO - 10.1016/j.cancergen.2013.01.002
M3 - Article
C2 - 23522749
AN - SCOPUS:84875919837
SN - 2210-7762
VL - 206
SP - 81
EP - 91
JO - Cancer genetics
JF - Cancer genetics
IS - 3
ER -
