TY - JOUR
T1 - Association of the 16q24.3 region gene variants rs1805007 and rs4785763 with heightened risk of melanoma in Latvian population
AU - Ozola, Aija
AU - Ruklisa, Dace
AU - Pjanova, Dace
N1 - Funding Information:
We would like to thank the Genome Database of the Latvian Population for providing data and DNA samples. This work was supported by TRANSCAN via The State Education Development Agency , Republic of Latvia with the grant GENMEL Z/15/1285 - PRL15/15 .
Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/12
Y1 - 2018/12
N2 - Chromosome region 16q24.3 has been shown to modify the risk for developing melanoma in genome-wide association studies (GWAS). This region includes at least three SNPs for which significant independent effects on melanoma risk have been demonstrated: rs258322 (CDK10 intron), rs4785763 (pseudogene AFG3L1P), and rs8059973 (flanking 5′UTR of DBNDD1). Also variants within the MC1R gene, located in the same region, are known to be associated with an increased melanoma risk. However, the exact risk these variants convey has never been estimated in the population of Latvia. Also the haplotypes of the 16q24.3 region and their relationship with melanoma have not been studied in this population before. To elucidate the associations of the variants from the 16q24.3 region with melanoma alongside their mutual interactions, we performed direct sequencing of the MC1R gene and genotyped the rs258322, rs4785763, and rs8059973 SNPs. In total, the study subjects included 479 individuals, comprising 255 melanoma patients and 224 controls. Univariate analyses of genotypes showed that only rs1805007 variant from MC1R gene, and two chromosome 16 SNPs, rs258322 and rs4785763, were nominally associated with an increased risk of melanoma. Multivariate models built by stepwise regression revealed that the contributions of rs1805007 and rs4785763 to melanoma risk are independent. Haplotype analyses demonstrated that rs1805007 and rs4785763 are independently associated with melanoma, whereas the impact of rs258322 to melanoma risk is related to rs1805007.
AB - Chromosome region 16q24.3 has been shown to modify the risk for developing melanoma in genome-wide association studies (GWAS). This region includes at least three SNPs for which significant independent effects on melanoma risk have been demonstrated: rs258322 (CDK10 intron), rs4785763 (pseudogene AFG3L1P), and rs8059973 (flanking 5′UTR of DBNDD1). Also variants within the MC1R gene, located in the same region, are known to be associated with an increased melanoma risk. However, the exact risk these variants convey has never been estimated in the population of Latvia. Also the haplotypes of the 16q24.3 region and their relationship with melanoma have not been studied in this population before. To elucidate the associations of the variants from the 16q24.3 region with melanoma alongside their mutual interactions, we performed direct sequencing of the MC1R gene and genotyped the rs258322, rs4785763, and rs8059973 SNPs. In total, the study subjects included 479 individuals, comprising 255 melanoma patients and 224 controls. Univariate analyses of genotypes showed that only rs1805007 variant from MC1R gene, and two chromosome 16 SNPs, rs258322 and rs4785763, were nominally associated with an increased risk of melanoma. Multivariate models built by stepwise regression revealed that the contributions of rs1805007 and rs4785763 to melanoma risk are independent. Haplotype analyses demonstrated that rs1805007 and rs4785763 are independently associated with melanoma, whereas the impact of rs258322 to melanoma risk is related to rs1805007.
KW - Case-control study
KW - Chromosome 16
KW - Genetic variation
KW - MC1R
KW - Melanoma
UR - http://www.scopus.com/inward/record.url?scp=85051813163&partnerID=8YFLogxK
U2 - 10.1016/j.mgene.2018.08.003
DO - 10.1016/j.mgene.2018.08.003
M3 - Article
AN - SCOPUS:85051813163
SN - 2214-5400
VL - 18
SP - 87
EP - 92
JO - Meta Gene
JF - Meta Gene
ER -