Variant "MDM4:c.*32C>A"
Search results: 3 records
Variant information
Gene:
MDM4 
Variant:
MDM4:c.*32C>A 
Genomic location:
chr1:204518842(hg19) 
HGVS:
SO Term RefSeq
protein_coding NM_002393.4:c.*32C>A
protein_coding NM_001204171.1:c.*32C>A
protein_coding NM_001204172.1:c.*32C>A
protein_coding NM_001278516.1:c.*1014C>A
protein_coding NM_001278517.1:c.*32C>A
protein_coding NM_001278518.1:c.*675C>A
protein_coding NM_001278519.1:c.*32C>A
show all
Alias:
MDM4:rs4245739A>C 
dbSNP ID:
rs4245739  
GWAS trait:
estrogen-receptor negative breast cancer,breast carcinoma,prostate carcinoma,triple-negative breast cancer,systolic blood pressure,diastolic blood pressure,smoking status measurement 
Modifier statisitcs
Record:
3 
Disorder:
3 
Reference:
3 
Effect type:
Expressivity(3)  
Modifier effect:
Altered susceptibility(2) ,Risk factor(1)  
Details：
  • Target disease:
    Breast Cancer (DOID_1612)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    Jinan set: OR=0.55, 95% CI: 0.40-0.76, P=2.3 × 10(-4); huaian set: OR= 0.41, 95% CI: 0.25-0.67, P=3.1 × 10(-4) 
    Effect:
    The MDM4 rs4245739 AC and CC genotypes were significantly associated with decreased breast cancer risk
    Alias in reference:
    MDM4:rs4245739A>C
    Reference:
    PMID23793604
    Title:
    Functional MDM4 rs4245739 genetic variant, alone and in combination with P53 Arg72Pro polymorphism, contributes to breast cancer susceptibility.
    Species studied:
    Human
    Abstract:
    The oncoprotein MDM4 plays an essential role in P53 tumor suppressor pathway through negative regulation of P53 function. It has been reported that the rs4245739 A>C polymorphism located in the MDM4 3'-untranslated region creates a miR-191 target site and results in decreased MDM4 expression. Therefore, we investigated the association of the MDM4 rs4245739 polymorphism as well as the P53 Arg72Pro genetic variant with the breast cancer risk. Genotypes were determined in two independent case-control sets consisting of 1100 breast cancer cases and 1400 controls from two regions of China. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. Our results demonstrated that the MDM4 rs4245739 AC and CC genotypes were significantly associated with decreased breast cancer risk compared to the AA genotype in both the case-control sets (Jinan set: OR=0.55, 95% CI 0.40-0.76, P=2.3×10(-4); Huaian set: OR=0.41, 95% CI 0.25-0.67, P=3.1×10(-4)). The P53 Arg/Pro genotype or Pro/Pro genotype was significantly associated with an increased risk of developing breast cancer, compared to the P53 Arg/Arg genotype in both the case-control sets (all P<0.05). Interestingly, we observed a combinational effect between MDM4 rs4245739 and P53 Arg72Pro variants in attenuating breast cancer risk, highlighting the importance of the P53 tumor suppressor pathway genes during malignant transformation. Our results also support the hypothesis that genetic variants interrupting miRNA-mediated gene regulation might be important genetic modifiers of breast cancer risk.
  • Target disease:
    Cancer (DOID_162)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered susceptibility 
    Evidence:
    OR=0.848, 95% CI: 0.765-0.941, P=0.002 
    Effect:
    The rs4245739 polymorphism may contribute to a decreased cancer susceptibility and support the hypothesis that genetic variants in the MDM4 genes act as important modifiers of cancer risk.
    Alias in reference:
    MDM4:c.*32C>A
    Reference:
    PMID27738340
    Title:
    A PRISMA-compliant meta-analysis of MDM4 genetic variants and cancer susceptibility.
    Species studied:
    Human
    Abstract:
    Molecular epidemiological research suggests that mouse double minute 4 (MDM4) polymorphisms may be associated with cancer susceptibility, but results remain controversial. To derive a more precise evaluation, we performed a PRISMA compliant meta-analysis focused on five single nucleotide polymorphisms (rs11801299, rs1380576, rs10900598, rs1563828, and rs4245739) of MDM4. Overall, 23 studies involving 22,218 cases and 55,033 controls were analyzed. The results showed that rs4245739 was significantly associated with a decreased cancer risk in the allelic (C vs. A: odds ratio [OR] = 0.848, 95% confidence interval [CI] = 0.765-0.941, P = 0.002), heterozygous (AC vs. AA: OR = 0.831, 95% CI = 0.735-0.939, P = 0.003), and dominant (AC+CC vs. A: OR = 0.823, 95% CI = 0.727-0.932, P = 0.002) models. The association was more prominent in Asians. No significant association was found using any genetic model for the rs11801299, rs1380576, rs10900598, and rs1563828 SNPs. These results indicate that the rs4245739 polymorphism may contribute to a decreased cancer susceptibility and support the hypothesis that genetic variants in the MDM4 genes act as important modifiers of cancer risk.
  • Target disease:
    Non-Hodgkin Lymphoma (DOID_0060060)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered susceptibility 
    Evidence:
    OR=0.45, 95% CI: 0.24-0.85, P=0.014 
    Effect:
    The TP53 Arg72Pro and the MDM4 rs4245739 polymorphisms contribute to NHL susceptibility
    Alias in reference:
    MDM4:c.*32C>A
    Reference:
    PMID25203442
    Title:
    The functional TP53 rs1042522 and MDM4 rs4245739 genetic variants contribute to Non-Hodgkin lymphoma risk.
    Species studied:
    Human
    Abstract:
    As a heterogeneous kind of malignances, Non-Hodgkin lymphoma (NHL) is the most common hematologic cancer worldwide with the significantly increased morbidity in China. Accumulated evidences demonstrated that oncoprotein MDM4 plays a crucial role in the TP53 tumor suppressor signaling pathway. An rs4245739 A>C polymorphism locating in the MDM4 3'-untranslated region creates a miR-191 target site and results in allele-specific MDM4 expression. In this study, we examined the association between this polymorphism as well as the TP53 Arg72Pro (rs1042522 G>C) genetic variant and Non-Hodgkin Lymphoma (NHL) risk in a Chinese Han population. Genotypes were determined in 200 NHL cases and 400 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. We found significantly increased NHL risk among carriers of the TP53 72Pro allele compared with those with the 72Arg allele (P=0.002 for the Pro/Pro genotype). We also observed a significantly decreased NHL risks among carriers of the MDM4 rs4245739 C allele compared with those with the A allele in Chinese (P=0.014 for the AC genotype). Stratified analyses revealed the associations between these SNPs and NHL risk are especially noteworthy in young or male individuals. Additionally, the associations are much pronounced in NHL patients with B-cell lymphomas or grade 3 or 4 disease. Our results indicate that the TP53 Arg72Pro and the MDM4 rs4245739 polymorphisms contribute to NHL susceptibility and support the hypothesis that genetic variants in the TP53 pathway genes can act as important modifiers of NHL risk.