Variant "CASP8:c.1030G>C(p.Asp344His)"
Search results: 7 records
Variant information
Gene:
CASP8 
Variant:
CASP8:c.1030G>C(p.Asp344His) 
Genomic location:
chr2:202149589(hg19) 
HGVS:
SO Term RefSeq
protein_coding NM_001080125.1:c.1030G>C(p.Asp344His)
protein_coding NM_001228.4:c.904G>C(p.Asp302His)
protein_coding NM_033355.3:c.853G>C(p.Asp285His)
protein_coding NM_001080124.1:c.808G>C(p.Asp270His)
protein_coding NM_033356.3:c.808G>C(p.Asp270His)
protein_coding 2Y1L:C_240-C_285:NM_033355.3:c.853G>C
protein_coding NM_139163.3:c.*3789C>G
protein_coding NM_033358.3:c.*7927G>C
protein_coding NM_001127391.2:c.*3789C>G
protein_coding NM_001289993.1:c.*3789C>G
pseudogene NR_110620.1:n.*3405C>G
pseudogene NR_111983.1:n.1367G>C
show all
Alias:
CASP8:D302H 
dbSNP ID:
rs1045485  
GWAS trait:
no data 
Modifier statisitcs
Record:
7 
Disorder:
4 
Reference:
5 
Effect type:
Expressivity(7)  
Modifier effect:
Risk factor(5) ,Altered onset time(2)  
Details：
  • Target disease:
    Achilles Bursitis (DOID_12857)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    P=0.031 
    Effect:
    The CASP8 I-G (rs3834129-rs1045485) inferred allele combination was associated with increased risk of TEN
    Alias in reference:
    CASP8:c.1030G>C(p.Asp344His)
    Reference:
    PMID27541197
    Title:
    Polymorphisms within the COL5A1 gene and regulators of the extracellular matrix modify the risk of Achilles tendon pathology in a British case-control study.
    Species studied:
    Human
    Abstract:
    Several genetic loci have been associated with risk of Achilles tendon pathology (ATP) within South African and Australian populations. The aim of this study was, therefore, to evaluate eight previously implicated genetic variants in an independent British population. A total of 130 asymptomatic controls (CON) and 112 participants clinically diagnosed with ATP comprising 87 individuals with chronic Achilles tendinopathy (TEN) and 25 with Achilles tendon ruptures (RUP) were included. All participants were genotyped for variants within the COL5A1, MIR608, IL-1β, IL-6 and CASP8 genes. Primary findings implicated COL5A1 and CASP8. Three inferred allele combinations constructed from COL5A1 rs12722, rs3196378 and rs71746744 were identified as risk modifiers. The T-C-D combination was associated with increased risk of ATP (P=0.023) and RUP (P<0.001), the C-A-I combination was associated with increased risk of ATP (P=0.011), TEN (P=0.011) and RUP (P=0.011) and the C-C-D combination was associated with decreased risk of ATP (P=0.011) and RUP (P=0.004). The CASP8 rs3834129 DD genotype was associated with decreased risk of TEN (P=0.020, odds ratio: 0.45, 95% confidence interval: 0.22-0.90) and the CASP8 I-G (rs3834129-rs1045485) inferred allele combination was associated with increased risk of TEN (P=0.031). This study further highlights the importance of polymorphisms within COL5A1 and CASP8 in the aetiology of ATP.
  • Target disease:
    Asthma (DOID_2841)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    P=0.033 
    Effect:
    rs1045485 in CASP8 was modestly associated with asthma in the Hispanic (P=0.033) populations,
    Alias in reference:
    CASP8:c.1030G>C(p.Asp344His)
    Reference:
    PMID18823309
    Title:
    Association of polymorphisms in CASP10 and CASP8 with FEV(1)/FVC and bronchial hyperresponsiveness in ethnically diverse asthmatics.
    Species studied:
    Human
    Abstract:
    Several chromosomal regions have been identified using family-based linkage analysis to contain genes contributing to the development of asthma and allergic disorders. One of these regions, chromosome 2q32-q33, contains a gene cluster containing CFLAR, CASP10 and CASP8. These genes regulate the extrinsic apoptosis pathway utilized by several types of immune and structural cells that have been implicated in the pathogenesis of asthma.
  • Target disease:
    Breast Cancer (DOID_1612)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered onset time 
    Evidence:
    Assessment of genotype–phenotype associations 
    Effect:
    Ten variants were found to be significantly associated with early onset cancer
    Alias in reference:
    CASP8:c.1030G>C(p.Asp344His)
    Reference:
    PMID26052370
    Title:
    Ten modifiers of BRCA1 penetrance validated in a Norwegian series.
    Species studied:
    Human
    Abstract:
    Common genetic variants have been shown to modify BRCA1 penetrance. The aim of this study was to validate these reports in a special cohort of Norwegian BRCA1 mutation carriers that were selected for their extreme age of onset of disease.
  • Target disease:
    Breast Cancer (DOID_1612)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    Per-allele HR=0.85; 95% CI: 0.76-0.97; P(trend) = 0.011 
    Effect:
    CASP8 D302H decreases breast and ovarian cancer risk for BRCA1 mutation carriers
    Alias in reference:
    CASP8:c.1030G>C(p.Asp344His)
    Reference:
    PMID20978178
    Title:
    Association of the variants CASP8 D302H and CASP10 V410I with breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.
    Species studied:
    Human
    Abstract:
    The genes caspase-8 (CASP8) and caspase-10 (CASP10) functionally cooperate and play a key role in the initiation of apoptosis. Suppression of apoptosis is one of the major mechanisms underlying the origin and progression of cancer. Previous case-control studies have indicated that the polymorphisms CASP8 D302H and CASP10 V410I are associated with a reduced risk of breast cancer in the general population.
  • Target disease:
    Breast Cancer (DOID_1612)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    OR=3.41, 95% CI: 1.33-8.78, P=0.01 
    Effect:
    The CASP8 D302H polymorphism diminishes the high risk of BC conferred by BRCA1 and BRCA2 mutations, making possible that some of the carriers could escape from suffering BC along their life span.
    Alias in reference:
    CASP8:D302H
    Reference:
    PMID19214744
    Title:
    CASP8 D302H polymorphism delays the age of onset of breast cancer in BRCA1 and BRCA2 carriers.
    Species studied:
    Human
    Abstract:
    The polymorphic genetic differences among individuals may modify the high risk for breast cancer (BC) and/or ovarian cancer (OC) susceptibility conferred by BRCA1 and BRCA2 mutations. In the present study we investigate the relevance of RAD51 -135C > G, TP53 R72P, NQO1*2 and CASP8 D302H polymorphisms as potential modifiers of BC and/or OC susceptibility conferred by these mutations. The study group encompasses 390 BRCA1/BRCA2 mutation carriers (182 affected with BC and/or OC and 208 unaffected) of 131 unrelated families studied in the Program of Genetic Counselling on Cancer of Valencia Community. The polymorphisms were detected in genomic DNA by ASRA method or real time PCR using fluorescently labeled probes. We found similar incidence of RAD51 -135C > G, TP53 R72P and NQO1*2 polymorphisms among affected and unaffected individuals considering BRCA1/BRCA2 mutations together and separately. However, the CASP8 D302H polymorphism was strongly associated with the absence of BC [OR = 3.41 (95% CI 1.33-8.78, P = 0.01)]. In fact, in the females with CASP8 D302H polymorphism the BC appeared at a median age of 58 in opposition to the 47 years observed for the wild type subjects (P = 0.03). Furthermore, the CASP8 D302H positive females showed a 50% probability of being free of BC by the age of 78 versus the 2% of the CASP8 negative ones. Our results support that the presence of the CASP8 D302H polymorphism diminishes the high risk of BC conferred by BRCA1 and BRCA2 mutations, making possible that some of the carriers could escape from suffering BC along their life span.
  • Target disease:
    Ovarian Cancer (DOID_2394)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered onset time 
    Evidence:
    Assessment of genotype–phenotype associations 
    Effect:
    Ten variants were found to be significantly associated with early onset cancer
    Alias in reference:
    CASP8:c.1030G>C(p.Asp344His)
    Reference:
    PMID26052370
    Title:
    Ten modifiers of BRCA1 penetrance validated in a Norwegian series.
    Species studied:
    Human
    Abstract:
    Common genetic variants have been shown to modify BRCA1 penetrance. The aim of this study was to validate these reports in a special cohort of Norwegian BRCA1 mutation carriers that were selected for their extreme age of onset of disease.
  • Target disease:
    Ovarian Cancer (DOID_2394)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    Per-allele HR=0.69; 95% CI: 0.53-0.89; P(trend) = 0.004 
    Effect:
    CASP8 D302H decreases breast and ovarian cancer risk for BRCA1 mutation carriers
    Alias in reference:
    CASP8:c.1030G>C(p.Asp344His)
    Reference:
    PMID20978178
    Title:
    Association of the variants CASP8 D302H and CASP10 V410I with breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers.
    Species studied:
    Human
    Abstract:
    The genes caspase-8 (CASP8) and caspase-10 (CASP10) functionally cooperate and play a key role in the initiation of apoptosis. Suppression of apoptosis is one of the major mechanisms underlying the origin and progression of cancer. Previous case-control studies have indicated that the polymorphisms CASP8 D302H and CASP10 V410I are associated with a reduced risk of breast cancer in the general population.