TP53 rs78392786: Cancer Susceptibility and the 3' UTR
The rs78392786 variant is a single-nucleotide polymorphism located in the 3' untranslated region of the TP53 tumor suppressor gene. It acts as a hypomorphic alteration that interferes with normal polyadenylation and post-transcriptional processing of TP53 mRNA. Research has statistically linked this variant to an increased susceptibility to certain neoplasms, including basal cell carcinoma and glioma, though overall clinical evidence remains limited.
What each genotype means
Typical TP53 polyadenylation
This is the most common genotype, representing the standard sequence for the TP53 3' UTR region. Individuals with this genotype do not carry the specific hypomorphic variant associated with altered polyadenylation and elevated cancer risk. This profile is considered the baseline for this genetic location.
This is the major allele genotype, found in the vast majority of the global population.
Elevated cancer risk carrier
This genotype indicates the presence of one copy of the rs78392786 variant, which is located in the 3' UTR of the TP53 gene. Research suggests this variant can impair proper polyadenylation of TP53 mRNA, potentially leading to reduced p53 protein function and an increased statistical risk for certain cancers, such as basal cell carcinoma and glioma. As this is a complex genetic association, individuals should discuss their overall health history and cancer screening needs with a qualified healthcare provider.
This is a rare genotype, observed with a minor allele frequency of approximately 0.001 to 0.003 in European ancestries.
Increased cancer risk profile
This genotype indicates the presence of two copies of the rs78392786 variant. This variant is known to interfere with the normal polyadenylation process of the TP53 gene, which is critical for tumor suppression. Studies have linked this variant to a significantly elevated risk for specific malignancies, including basal cell carcinoma and glioma. Because this is a rare genetic finding, it is recommended to consult with a genetic counselor or physician to understand its implications in the context of your personal and family medical history.
This genotype is extremely rare in the general population, occurring at a frequency consistent with the low prevalence of the minor allele.
Genomic Location and Biological Mechanism
The single-nucleotide variant rs78392786 is mapped to chromosome 17 within the 3' untranslated region (3' UTR) of the TP53 gene. Unlike classical protein-truncating or missense mutations in TP53 that change amino acid sequences, this variant lies in the regulatory sequence that directs mRNA polyadenylation. The polyadenylation signal (canonical sequence AATAAA) is essential for cleavage and the addition of a poly(A) tail, which stabilizes mRNA transcripts and ensures efficient nuclear export and translation. Alteration of this signal impairs normal 3'-end processing, resulting in reduced levels of mature p53 mRNA transcripts. Because functional p53 protein is still produced—albeit at lower cellular quantities—this polymorphism is classified functionally as a hypomorphic allele rather than a complete loss-of-function mutation.
The Biological Role of TP53
The TP53 gene encodes the tumor protein p53, universally recognized as the 'guardian of the genome.' Under baseline physiological conditions, p53 coordinates critical cellular responses to DNA damage, oxidative stress, oncogene activation, and hypoxia. When cellular harm is detected, p53 functions as a transcription factor that upregulates target genes responsible for transient cell-cycle arrest, permitting enzymatic DNA repair mechanisms to resolve lesions. If genomic damage is irreparable, p53 initiates programmed cell death (apoptosis) or permanent replicative senescence, preventing the proliferation of potentially malignant cells. Classical high-penetrance pathogenic germline variants in TP53 cause Li-Fraumeni syndrome, a severe hereditary cancer predisposition. In contrast, 3' UTR regulatory variants like rs78392786 lead to modest quantitative reductions in p53 levels, conferring subtle, tissue-specific cancer risks rather than early-onset childhood syndromes.
Clinical Research and Cancer Risk Associations
Genome-wide association studies and molecular oncology analyses have linked functional TP53 3' UTR polyadenylation variants to increased susceptibility to specific adult-onset malignancies, as documented in published studies on [cancer susceptibility and TP53 polyadenylation](https://pubmed.ncbi.nlm.nih.gov/21946351/). In population-level studies, the minor allele demonstrates significant statistical associations with cutaneous basal cell carcinoma (OR ~1.7 to 2.2) and neuroepithelial tumors such as glioma (OR >2.0). Additional associations have been identified with prostate cancer and colorectal adenomas, while notably lacking the classic breast cancer risks typical of high-penetrance Li-Fraumeni mutations. Despite these statistically robust epidemiological signals, the evidence strength for direct individual clinical utility remains classified as limited because the absolute lifetime penetrance is low and the variant operates predominantly as a polygenic risk factor rather than a deterministic single-gene diagnostic marker.
Population Prevalence and Ancestral Patterns
Variant rs78392786 is relatively rare in the broader human population. Population genomics databases such as gnomAD and focused European cohorts report a minor allele frequency typically ranging between 0.001 and 0.003 (approximately 0.1% to 0.3%) in individuals of European ancestry. Because this allele is infrequent, homozygosity is exceedingly rare, and the vast majority of documented carriers are heterozygous. Across non-European ancestral populations, data remains relatively thin, with the variant appearing at similarly low frequencies or absent in specific continental groups. Because of this rarity, wide population screening is not routine, and prevalence estimates may vary between specific regional datasets.
Interpreting Results and Clinical Perspective
Detecting a regulatory variant such as rs78392786 does not mean an individual is diagnosed with cancer or will inevitably develop a tumor. Instead, personal genomics results for this marker describe a modest shift in statistical baseline susceptibility relative to the general population. Cancer development is a complex, multifactorial process influenced by cumulative lifestyle factors, environmental exposures like ultraviolet radiation, age, and polygenic background. Patients should not alter medical care or embark on invasive screening procedures based solely on consumer genomic reports. Individuals with extensive personal or family histories of malignancy should consult a board-certified genetic counselor or medical geneticist to review their comprehensive pedigree and consider formal, clinical-grade multigene panel testing.
How common is this variant?
The rs78392786 variant is a rare germline alteration, with a minor allele frequency estimated between 0.001 and 0.003 (0.1% to 0.3%) in European populations, and it is observed at very low or uncharacterized rates in other ancestral groups.
Frequently asked questions
Does having the rs78392786 variant mean I will get cancer?
No. Carrying this variant only indicates a modest statistical increase in relative susceptibility for specific cancers, such as basal cell carcinoma and glioma. Most people who carry this allele never develop these malignancies, as cancer etiology is influenced by many other genetic and environmental factors.
Is rs78392786 linked to Li-Fraumeni syndrome?
Unlike traditional pathogenic TP53 coding mutations that cause classical Li-Fraumeni syndrome, rs78392786 is a hypomorphic regulatory variant in the 3' UTR. It results in a partial decrease in p53 expression and confers moderate risk increases for specific tumors without causing the full, high-penetrance childhood tumor spectrum seen in Li-Fraumeni syndrome.
How does this variant affect the p53 protein?
The rs78392786 variant does not alter the amino acid sequence of the p53 protein. Instead, it disrupts the polyadenylation recognition motif in the mRNA transcript, impairing proper 3'-end processing and leading to lower steady-state levels of p53 cellular expression.
What should I do if my genetic data shows this variant?
A consumer genetic finding should not be used as a standalone diagnostic tool. If you have concerns or a strong family history of cancer, discuss your results with a healthcare professional or genetic counselor who can evaluate your comprehensive clinical history.
Sources & further reading
Educational information only, last refreshed 9/8/2026. Not medical advice — these associations describe population statistics, not individual predictions.
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Get my report — $29Related variants in TP53
Pathogenic missense variant (p.Arg248Gln) associated with Li-Fraumeni syndrome.
Functional codon 72 polymorphism (Arg72Pro) affecting apoptotic capability and associated with differential susceptibility to multiple cancer types.
Functional 3' UTR polyadenylation signal polymorphism altering TP53 transcription termination, showing population-specific baseline carrier frequencies across global groups.
Pathogenic hotspot variant (p.Arg273His) in TP53 predisposing carriers to early-onset sarcomas, breast cancers, and leukemias.
Li-Fraumeni syndrome missense variant (p.Arg248Trp) causing loss of tumor suppressor function and multi-cancer predisposition.
Synonymous and regulatory variant in linkage with TP53 codon 72 that modulates blastocyst implantation competence and the risk of recurrent implantation failure.