rs78378222
This is a 3 prime utr variant variant in the TP53 gene.
▶GWAS Catalog Trait Associations (57)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
GWAS Catalog Trait Associations (57)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
▶ClinVar annotation
Basal cell carcinoma, susceptibility to, 7 (BCC7); Hereditary cancer-predisposing syndrome; Li-Fraumeni syndrome 1 (LFS); TP53-related disorder
View on ClinVar →▶Research that mentions this SNP (6)
▶A functional variant on 20q13.33 related to glioma risk alters enhancer activity and modulates expression of multiple genesFunctionalN=646Ali MW et al.(2021)· Human Mutation
This functional study identifies rs3761124 as a causal variant on 20q13.33 that modulates glioma risk through enhancer activity and altered expression of multiple genes, particularly STMN3. Using luciferase assays, CRISPR-Cas9 editing, and eQTL analysis across 646 individuals from brain tissue and tumor cohorts, the authors demonstrate that rs3761124 has allele-specific effects on enhancer activity and consistently associates with STMN3 expression. Colocalization analysis (PP4=0.82) supports rs3761124 as the causal variant underlying the GWAS signal at this locus.
▶Age‐specific genome‐wide association study in glioblastoma identifies increased proportion of ‘lower grade glioma’‐like features associated with younger ageAssociationN=15,094Quinn T. Ostrom et al.(2018)· International Journal of Cancer
Age-stratified genome-wide association study of 4,512 glioblastoma cases and 10,582 controls identified age-specific genetic effects on disease susceptibility. SNPs at 7p11.2 (rs723527, rs11979158 near EGFR) showed increased association in older individuals (age 54+, OR=1.28-1.42), while a lower-grade glioma-associated SNP at 8q24.21 (rs55705857) was associated with younger diagnosis (age 18-53, OR=1.76, p=9.30×10−11). IDH1/2 mutations occurred in 15% of younger GBM cases versus 0.8-2.1% in older cases, suggesting many younger cases represent 'secondary GBM' with LGG-like features.
▶Further Confirmation of Germline Glioma Risk Variant rs78378222 inTP53and Its Implication in Tumor Tissues via Integrative Analysis of TCGA DataAssociationN=6,811Wang Z. et al.(2015)· Human Mutation
This study confirms that rs78378222:A>C, a rare germline variant in the TP53 3' untranslated region, confers strong glioma risk (OR=3.14, p=6.48×10⁻¹¹) in a GWAS of 1,856 cases and 4,955 controls. Integrative analysis of TCGA data revealed that the risk allele C disrupts mRNA termination causing aberrant transcripts (~3 kb longer), while the protective allele A is somatically deleted in glioblastoma tissues, supporting a two-hit mechanism in tumor development.
▶Genetic variants at chromosome 8q24, colorectal epithelial cell proliferation, and risk for incident, sporadic colorectal adenomasMeta-analysisN=170,737Baiyu Yang et al.(2014)· Molecular Carcinogenesis
A meta-analysis of 78 case-control studies (73,996 cases, 96,741 controls) found that the rs6983267 polymorphism on chromosome 8q24 was significantly associated with increased cancer risk across all genetic models (dominant: OR=1.19, 95% CI=1.13-1.26; recessive: OR=1.19, 95% CI=1.14-1.25; homozygous: OR=1.31, 95% CI=1.23-1.40). Stratified analyses showed significant associations for colorectal cancer, prostate cancer, and thyroid cancer in Caucasians, and lung cancer in Asians.
▶No evidence that associations of incident, sporadic colorectal adenoma with its major modifiable risk factors differ by chromosome 8q24 region rs6983267 genotypeMeta-analysisN=170,737Baiyu Yang et al.(2014)· Molecular Carcinogenesis
Meta-analysis of 78 case-control studies (73,996 cases, 96,741 controls, 170,737 total subjects) examining the association between 8q24 rs6983267 G/T polymorphism and cancer susceptibility. The G risk allele was significantly associated with increased cancer risk across all genetic models (dominant: OR=1.19, 95%CI=1.13-1.26; recessive: OR=1.19, 95%CI=1.14-1.25; homozygous: OR=1.31, 95%CI=1.23-1.40). Significant associations were found for colorectal cancer, prostate cancer, thyroid cancer, and lung cancer in ethnicity-stratified analyses.
▶Effect of TP53 codon 72 and MDM2 SNP309 polymorphisms on survival of gastric cancer among patients who receiving 5-fluorouracil-based postoperative adjuvant chemotherapyAssociationN=940Shizhi Wang et al.(2013)· Cancer Chemotherapy and Pharmacology
A cohort study of 940 gastric adenocarcinoma patients examined the association between TP53 codon 72 polymorphism (rs1042522, Arg72Pro) and MDM2 SNP309 (rs2279744) with survival outcomes. TP53 codon 72 polymorphism was significantly associated with poor survival in patients receiving 5-fluorouracil-based postoperative chemotherapy (adjusted HR=1.63, 95% CI=1.08-2.44), with particularly strong associations in the FOLFOX regimen (adjusted HR=4.47, 95% CI=1.21-16.55). MDM2 SNP309 showed no significant association with survival.
About TP53
This gene encodes a tumor suppressor protein containing transcriptional activation, DNA binding, and oligomerization domains. The encoded protein responds to diverse cellular stresses to regulate expression of target genes, thereby inducing cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. Mutations in this gene are associated with a variety of human cancers, including hereditary cancers such as Li-Fraumeni syndrome. Alternative splicing of this gene and the use of alternate promoters result in multiple transcript variants and isoforms. Additional isoforms have also been shown to result from the use of alternate translation initiation codons from identical transcript variants (PMIDs: 12032546, 20937277). [provided by RefSeq, Dec 2016]
View all TP53 variants →Gene information from NCBI Gene. Variant classifications from ClinVar.
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