Variant "CDKN2A:c.249A>G(p.Gly83Gly)"
Search result: 1 record
Variant information
Gene:
CDKN2A 
Variant:
CDKN2A:c.249A>G(p.Gly83Gly) 
Genomic location:
chr9:21971152(hg19) 
HGVS:
SO Term RefSeq
protein_coding NM_058195.3:c.249A>G(p.Gly83Gly)
protein_coding NM_001195132.1:c.206A>G(p.Glu69Gly)
protein_coding NM_000077.4:c.206A>G(p.Glu69Gly)
protein_coding NM_058197.4:c.*129A>G
pseudogene NR_024274.1:n.*3399T>C
dbSNP ID:
rs372670098  
GWAS trait:
no data 
Modifier statisitcs
Record:
1 
Disorder:
1 
Reference:
1 
Effect type:
Penetrance(1)  
Modifier effect:
Prevention of disease(1)  
Detail：
  • Target disease:
    Melanoma (DOID_1909)
    Effect type:
    Penetrance 
    Modifier effect:
    Prevention of disease 
    Evidence:
    Pedigree analysis 
    Effect:
    Improve the risk of melanoma
    Reference:
    PMID19484507
    Title:
    Protective effect of copy number polymorphism of glutathione S-transferase T1 gene on melanoma risk in presence of CDKN2A mutations, MC1R variants and host-related phenotypes.
    Species studied:
    Human
    Abstract:
    The effect of CDKN2A, the major high-risk melanoma susceptibility gene, has been shown to be modified by host-related phenotypes and variants of MC1R gene. The glutathione S-transferase (GSTs) genes, implicated in detoxification of metabolites after UV exposure, are candidates for modulating CDKN2A penetrance. Few case-control studies have investigated the effect of GSTs on melanoma risk, and have led to controversial results while these genes have not yet been studied in CDKN2A melanoma-prone families. We examined the effect of GSTP1, GSTM1 and GSTT1 genotypes on melanoma risk in 25 multi-generational melanoma-prone families with CDKN2A mutations, in presence of MC1R gene variants, sun exposure, and host-related phenotypes. These data included 195 genotyped subjects for all studied genes. We applied the GEE (Generalized Estimating Equations) approach to test for the effect of GSTs while adjusting for age, sex and CDKN2A mutation status and including successively MC1R, sun exposure and host factors in the model. No significant effect of null GSTM1 allele and GSTP1 variants (p.I105V, p.A114V) on melanoma risk was found. However, a significant protective effect of carrying >or=1 null GSTT1 allele was shown: OR(adjusted for age,sex,CDKN2A ) = 0.41 (0.18-0.94) and OR(adjusted for age,sex,CDKN2A,MC1R ) = 0.24 (0.15-0.58). Altogether, the factors modifying significantly the melanoma risk associated with CDKN2A mutations (stepwise procedure) were: MC1R and dysplastic nevi (increasing the risk) and GSTT1 (decreasing the risk). This study shows that even when a high-risk gene (CDKN2A) has been identified, multiple genetic modifiers influence melanoma risk.