Variant "GSTP1:p.Val114/Val114"
Search results: 2 records
Variant information
Gene:
GSTP1 
Variant:
GSTP1:p.Val114/Val114 
Genomic location:
chr11:67353579(hg19) 
HGVS:
SO Term RefSeq
protein_coding NM_000852.3:c.341C>T(p.Ala114Val)
Alias:
GSTP1:p.A114V 
dbSNP ID:
rs1138272  
GWAS trait:
no data 
Modifier statisitcs
Record:
2 
Disorder:
2 
Reference:
2 
Effect type:
Expressivity(1) ,Penetrance(1)  
Modifier effect:
Prevention of disease(1) ,Risk factor(1)  
Details：
  • Target disease:
    Cancer (DOID_162)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    P<0.002 
    Effect:
    The genetic modifier GSTP1 Val114/Val114 genotype may begin to define a high-risk genotype for cancer susceptibility in the pediatric population.
    Alias in reference:
    GSTP1:p.Val114/Val114
    Reference:
    PMID12241105
    Title:
    Identification of glutathione S-transferase (GST) polymorphisms in brain tumors and association with susceptibility to pediatric astrocytomas.
    Species studied:
    Human
    Abstract:
    Polymorphisms in the glutathione S-transferase (GST) genes, a superfamily that plays a key role in carcinogen metabolism, have been associated with an increased susceptibility to several types of cancer. We wished to evaluate whether variant allelic forms of GST isoenzymes were associated with an increased susceptibility for brain tumors and age of tumor onset. Here, we examined 394 brain tumors (221 adult and 173 pediatric cases consisting of 197 astrocytic and 197 non-astrocytic tumors) to determine the frequency of polymorphisms in the GSTM1, GSTT1, and GSTP1 genes compared to a healthy control population. Our data shows that the frequency of GST polymorphisms varies not only between adult and pediatric patients with brain tumors and healthy controls, but also between different histological subtypes of brain tumors occurring in pediatric patients. We found (i) a statistically significant increase in the frequency of the functional GSTM1 allele in high-grade pediatric astrocytomas (p < 0.002), (ii) a significant increase in the frequency of the rare GSTP1 variant Val114/Val114 in pediatric astrocytomas (p < 0.002), and (iii) a significant increase in the frequency of the rare GSTP1 Val114/Val114 genotype among pediatric tumors showing microsatellite instability (MSI) due to defects in mismatch repair (MMR) proteins (p = 0.003). Our results suggest that GSTM1 and GSTP1 polymorphisms may play a role in brain tumor susceptibility by histological subtype, particularly high-grade pediatric astrocytomas. Moreover, the presence of the genetic modifier GSTP1 Val114/Val14 genotype may begin to define a high-risk genotype for cancer susceptibility in the pediatric population.
  • Target disease:
    Melanoma (DOID_1909)
    Effect type:
    Penetrance 
    Modifier effect:
    Prevention of disease 
    Evidence:
    Pedigree analysis 
    Effect:
    Improve the risk of melanoma
    Alias in reference:
    GSTP1:p.A114V
    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.