|(C;C)||3||Live 3 years longer. Chemotherapy is more effective.|
|(C;G)||2||Slightly increased lifespan?|
|(G;G)||2||Common variant. Slightly shorter lifespan.|
For this particular SNP, the G allele encodes an arginine at position 72 of the protein (where there's normally a proline), and the SNP is commonly called the Arg72 variant, although P72R and Arg72Pro are also common in the literature.
[PMID 18256523] Minor allele homozygotes, i.e. rs1042522(C;C) genotypes, live on average 3 years longer than major allele (G;G) homozygotes, based on a study of 9,200+ Danish individuals. The increased longevity is speculated to be related to the increased apoptosis seen for this gain of function SNP, presumably due to "increased robustness" during the period of treatment after the diagnosis of life-threatening diseases such as cancer of certain types.
A study of 148 individuals with advanced nonsmall cell lung cancer (NSCLC) concluded rs1042522(G;G) genotypes were more likely to be resistant to first-line chemotherapy, especially the irinotecan plus cisplatin regimen, than those with (C;G) or (C;C) genotypes (60% vs 27%, p = .014). In multivariate analysis, the (G;G) genotype was strongly predictive for shorter progression-free survival (PFS) (hazard ratio [HR] = 1.952, p = .01).[PMID 18618574]
A study of 57 patients with advanced gastric cancer treated with paclitaxel and cisplatin combination chemotherapy found that rs1042522(G;G) and rs1042522(C;G) genotypes were significantly correlated with a lower response rate (and worse progression) to the combination chemotherapy when compared to rs1042522(C;C) homozygotes (35.7 vs. 66.7%, p-value 0.019).[PMID 19052714]
- [PMID 19193430] rs2279744, rs1042522, rs17878362 and rs1625895 associated with high grade endometrial cancer
23andMe blog African Americans with rs1042522(G;G) in the p53 gene were 2.15 times more likely to die of colorectal cancer than those with one or no copies of a G at this SNP. In Caucasians there was no association between survival and rs1042522.
23andMe blog rs1042522(C) might have had an easier time conceiving in colder temperatures
10.1073/pnas.0904280106 The P72 allele was found to be significantly enriched over the R72 allele among in vitro fertilization (IVF) patients. The P72 allele serves as a risk factor for implantation failure. LIF levels are significantly lower in cells with the P72 allele than in cells with the R72 allele, which may contribute to the decreased implantation and fertility associated with the P72 allele.
[PMID 19367277] Patients with variant TP53 genotypes either for the Arg72Pro or the PIN3 polymorphism were at increased risk of telangiectasia, a late skin side effect of radiotherapy following breast-conserving surgery. Odds ratios were 1.66 for 72Pro carriers and 1.95 for PIN3 A2 allele carriers. Carrying both variant alleles led to a doubling of risk.
|Disease Association||Defects in TP53 are a cause of choroid plexus papilloma (MIM:260500). Choroid plexus papilloma is a slow-growing benign tumor of the choroid plexus that often invades the leptomeninges. In children it is usually in a lateral ventricle but in adults it is more often in the fourth ventricle. Hydrocephalus is common, either from obstruction or from tumor secretion of cerebrospinal fluid. If it undergoes malignant transformation it is called a choroid plexus carcinoma. Primary choroid plexus tumors are rare and usually occur in early childhood.|
[PMID 19423538] Common Genetic Variation in TP53 and Risk of Human Papillomavirus Persistence and Progression to CIN3/Cancer Revisited
[PMID 19471604] Lack of association between p53 gene polymorphisms and primary open angle glaucoma in the Japanese population
[PMID 19505915] Association of Genetic Polymorphisms, mRNA Expression of p53 and p21 with Chronic Benzene Poisoning in a Chinese Occupational Population
[PMID 19521721] Accelerated decline in lung function in cigarette smokers is associated with TP53/MDM2 polymorphisms
[PMID 19286843] Polymorphisms of DNA damage response genes in radiation-related and sporadic papillary thyroid carcinoma
[PMID 19707196] The TP53 Arg72Pro and MDM2 309G>T polymorphisms are not associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers
[PMID 19834951] The Li-Fraumeni syndrome (LFS): a model for the initiation of p53 signatures in the distal Fallopian tube
[PMID 19837266] TP53 R72P and MDM2 SNP309 polymorphisms in modification of childhood acute lymphoblastic leukemia susceptibility
[PMID 20110284] Genotype and haplotype analysis of TP53 gene and the risk of pancreatic cancer: an association study in the Czech Republic
[PMID 20127253] The role of TP53 and p21 gene polymorphisms in breast cancer biology in a well specified and characterized German cohort
[PMID 20357201] Association of Polymorphisms of Tumor Necrosis Factor and Tumor Protein p53 with Primary Open Angle Glaucoma: A Replication Study of Ten Genes in A Chinese Population
[PMID 20512840] Association between TP53 gene ARG72PRO polymorphism and chromosome aberrations in human cancers
[PMID 20544687] Evidence that genetic variants of metabolic detoxication and cell cycle control are not related to gallbladder cancer risk in Chilean women
[PMID 20593380] p53 Pro72Arg polymorphism and prostate cancer in men of African descent
[PMID 20615891] TP53 Arg72Pro Polymorphism and Colorectal Cancer Risk: A Systematic Review and Meta-Analysis
[PMID 20587610] Examination of genetic polymorphisms in newborns for signatures of sex-specific prenatal selection
[PMID 20232390] Genetic variations of DNA repair genes and their prognostic significance in patients with acute myeloid leukemia
[PMID 21790896] Genetic and environmental predictors, endogenous hormones and growth factors and risk of estrogen receptor-positive breast cancer in Japanese women
[PMID 21843334] TP53 and MDM2 gene polymorphisms and risk of hepatocellular carcinoma in Italian patients
[PMID 22184967] [Association analysis of polymorphic loci of TP53 and NFKB1 genes with human age and longevity]
[PMID 22189267] Codon 72 polymorphism (rs1042522) of TP53 is associated with changes in diastolic blood pressure over time
[PMID 22251423] NAMPT (visfatin) and AKT1 genetic variants associate with myocardial infarction
[PMID 22336942] Investigation of the Effect of MDM2 SNP309 and TP53 Arg72Pro Polymorphisms on the Age of Onset of Cutaneous Melanoma
[PMID 22417303] Infrequent p53 gene mutation but UV gradient-like p53 protein positivity in keloids
[PMID 22294769] Mutations and polymorphisms in TP53 gene--an overview on the role in colorectal cancer.
[PMID 21838531] Crosstalk between the FGFR2 and TP53 genes in breast cancer: data from an association study and epistatic interaction analysis
[PMID 22532853] How Contemporary Human Reproductive Behaviors Influence the Role of Fertility-Related Genes: The Example of the P53 Gene
[PMID 22076708] Validation of Genetic Sequence Variants as Prognostic Factors in Early-Stage Head and Neck Squamous Cell Cancer Survival
|Disease||not specified CODON 72 POLYMORPHISM not provided Hereditary cancer-predisposing syndrome Li-Fraumeni syndrome 1|
|CLNDBN||not specified CODON 72 POLYMORPHISM, (rs1042522) not provided Hereditary cancer-predisposing syndrome Li-Fraumeni syndrome 1|
|HGVS||NC_000017.10:g.7579472G\x3d; NC_000017.10:g.7579472G>C; NC_000017.10:g.7579472G>T|
|CLNSRC||HGMD OMIM Allelic Variant|
|CLNACC||RCV000152112.1, RCV000013144.2, RCV000034639.1, RCV000079202.5, RCV000132165.2, RCV000144668.1, RCV000164487.1,|
[PMID 15450681] Tumor suppressor gene TP53 is genetically associated with schizophrenia in the Chinese population.
[PMID 15564288] Polymorphisms in XPD and TP53 and mutation in human lung cancer.
[PMID 16287156] Genetic polymorphisms in cell cycle regulatory genes MDM2 and TP53 are associated with susceptibility to lung cancer.
[PMID 16465622] Bladder cancer predisposition: a multigenic approach to DNA-repair and cell-cycle-control genes.
[PMID 16857995] Risk of non-Hodgkin lymphoma (NHL) in relation to germline variation in DNA repair and related genes.
[PMID 17096406] Germ-line genetic variation of TP53 in osteosarcoma.
[PMID 17301252] Common genetic variation in TP53 is associated with lung cancer risk and prognosis in African Americans and somatic mutations in lung tumors.
[PMID 17428325] Common variants in the ATM, BRCA1, BRCA2, CHEK2 and TP53 cancer susceptibility genes are unlikely to increase breast cancer risk.
[PMID 17449902] Genetic variation in TP53 and risk of breast cancer in a population-based case control study.
[PMID 17537232] Association of TP53 codon 72 polymorphism and the outcome of adjuvant therapy in breast cancer patients.
[PMID 17624591] Genetic variation of TP53, polycyclic aromatic hydrocarbon-related exposures, and breast cancer risk among women on Long Island, New York.
[PMID 18191955] Correlating observed odds ratios from lung cancer case-control studies to SNP functional scores predicted by bioinformatic tools.
[PMID 18298806] Do genetic factors protect for early onset lung cancer? A case control study before the age of 50 years.
[PMID 18433491] MDM2 gene SNP309 T/G and p53 gene SNP72 G/C do not influence diffuse large B-cell non-Hodgkin lymphoma onset or survival in central European Caucasians.
[PMID 18547414] Genotyping panel for assessing response to cancer chemotherapy.
[PMID 18640487] Association of donor inflammation- and apoptosis-related genotypes and delayed allograft function after kidney transplantation.
[PMID 18715757] Genetic associations with schizophrenia: meta-analyses of 12 candidate genes.
[PMID 18798306] Construction of a high resolution linkage disequilibrium map to evaluate common genetic variation in TP53 and neural tube defect risk in an Irish population.
[PMID 18805939] Functional genetic polymorphisms and female reproductive disorders: part II--endometriosis.
[PMID 18820009] Possible difference in frequencies of genetic polymorphisms of estrogen receptor alpha, estrogen metabolism and P53 genes between estrogen receptor-positive and -negative breast cancers.
[PMID 18854777] Germline genetic variations in drug action pathways predict clinical outcomes in advanced lung cancer treated with platinum-based chemotherapy.
[PMID 18978339] Large-scale evaluation of candidate genes identifies associations between DNA repair and genomic maintenance and development of benzene hematotoxicity.
[PMID 18990748] International Lung Cancer Consortium: pooled analysis of sequence variants in DNA repair and cell cycle pathways.
[PMID 19224585] Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic.
[PMID 19237173] Bcl2 -938C/A polymorphism carries increased risk of biochemical recurrence after radical prostatectomy.
[PMID 19276375] Single nucleotide polymorphisms in the TP53 region and susceptibility to invasive epithelial ovarian cancer.
[PMID 19426493] A case-control study on the combined effects of p53 and p73 polymorphisms on head and neck cancer risk in an Italian population.
[PMID 19470478] Single-nucleotide polymorphisms in the p53 pathway regulate fertility in humans.
[PMID 19482343] Polymorphisms in HPV E6/E7 protein interacted genes and risk of cervical cancer in Chinese women: a case-control analysis.
[PMID 19542078] TP53 PIN3 and MDM2 SNP309 polymorphisms as genetic modifiers in the Li-Fraumeni syndrome: impact on age at first diagnosis.
[PMID 19625214] TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies.
[PMID 19657586] Association study between P53 and P73 gene polymorphisms and the sporadic late-onset form of Alzheimer's disease.
[PMID 19750108] Decreased PM10 exposure attenuates age-related lung function decline: genetic variants in p53, p21, and CCND1 modify this effect.
[PMID 19784392] Primary open angle glaucoma in a Caucasian population is associated with the p53 codon 72 polymorphism.
[PMID 19822020] Genetic factors associated with intestinal metaplasia in a high risk Singapore-Chinese population: a cohort study.
[PMID 19911060] Persistence criteria for susceptibility genes for schizophrenia: a discussion from an evolutionary viewpoint.
[PMID 20003265] Extent of differential allelic expression of candidate breast cancer genes is similar in blood and breast.
[PMID 20436704] TP53 mutations in Korean patients with non-small cell lung cancer.
[PMID 20452958] Single-nucleotide polymorphisms in the p53 signaling pathway.
[PMID 20455025] Survey of familial glioma and role of germline p16INK4A/p14ARF and p53 mutation.
[PMID 20935061] A novel functional DEC1 promoter polymorphism -249T>C reduces risk of squamous cell carcinoma of the head and neck.
[PMID 21029772] Genomic DNA extraction from whole blood stored from 15- to 30-years at -20 degrees C by rapid phenol-chloroform protocol: a useful tool for genetic epidemiology studies.
[PMID 21115003] TP53 polymorphisms in gliomas from Indian patients: Study of codon 72 genotype, rs1642785, rs1800370 and 16 base pair insertion in intron-3.
[PMID 21146886] Association between polymorphisms in RAPGEF1, TP53, NRF1 and type 2 diabetes in Chinese Han population.
[PMID 21252575] TP53 codon 72 polymorphism is associated with coronary artery disease in Chilean subjects.
[PMID 21283750] Studies of the association of Arg72Pro of tumor suppressor protein p53 with type 2 diabetes in a combined analysis of 55,521 Europeans.
[PMID 21437228] Using epidemiology and genomics to understand osteosarcoma etiology.
[PMID 21708280] Candidate gene studies in gallbladder cancer: a systematic review and meta-analysis.
[PMID 21741128] TP53 Arg72Pro polymorphism in Turkish patients with sporadic amyotrophic lateral sclerosis.
[PMID 21810023] Coordination of TP53 abnormalities in breast cancer: data from analysis of TP53 polymorphisms, loss of heterozygosity, methylation, and mutations.
[PMID 21841506] Combined effect of genetic polymorphisms in P53, P73, and MDM2 on non-small cell lung cancer survival.
[PMID 21897271] Analysis of 4 single-nucleotide polymorphisms in relation to cervical dysplasia and cancer development using a high-throughput ligation-detection reaction procedure.
[PMID 22178231] Polymorphisms of TP53 are markers of bladder cancer vulnerability and prognosis.
|qualified_impact||Low clinical importance, Uncertain pathogenic|
|summary||This is a common variant was first reported as a polymorphism. It has since had mixed associations with cancer: Storey et al. conclude a 7x *increased* risk of HPV cancer for homozygotes vs hets, but Jones et al. find a 1.98x *decreased* risk for colorectal cancer. This variant may have significant impact on particular cancers, but it is unclear what effect it has on the overall burden of cancer.|
[PMID 23192612] Association of common WRAP 53 variant with ovarian cancer risk in the Polish population
[PMID 23207172] The p53 Codon 72 Polymorphism (rs1042522) is Associated with Proliferative Vitreoretinopathy: The Retina 4 Project
[PMID 23210739] Association of MDM2 and p53 Polymorphisms with the Advancement of Cervical Carcinoma
[PMID 23269546] The p53 codon 72 (Arg72Pro) polymorphism is associated with the degree of insulin resistance in type 2 diabetic subjects: a cross-sectional study
[PMID 23441193] Accuracy of p53 Codon 72 Polymorphism Status Determined by Multiple Laboratory Methods: A Latent Class Model Analysis
[PMID 23534750] Polymorphisms in TP53 (rs1042522), p16 (rs11515 and rs3088440) and NQO1 (rs1800566) Genes in Thai Cervical Cancer Patients with HPV 16 Infection
[PMID 23632240] Promoter polymorphisms of pri-miR-34b/c are associated with hepatocellular carcinoma
[PMID 23653000] CXCL12 and TP53 genetic polymorphisms as markers of susceptibility in a Brazilian children population with acute lymphoblastic leukemia (ALL)
[PMID 23744327] [Association of P53 gene polymorphisms with susceptibility to endometriosis]
[PMID 23360829] Association between polymorphisms in the genes for tumor suppressor protein p53 and its regulator NAD(P)H: quinone oxidoreductase 1 (NQO1) and schizophrenia in a Syrian study cohort
[PMID 23837945] Association of p53 and MDM2 polymorphisms with risk of human papillomavirus (HPV)-related esophageal squamous cell carcinoma (ESCC)
[PMID 23906684] Genetic associations with coronary heart disease: Meta-analyses of 12 candidate genetic variants
[PMID 23936089] Polymorphisms in DNA-Repair Genes in a Cohort of Prostate Cancer Patients from Different Areas in Spain: Heterogeneity between Populations as a Confounding Factor in Association Studies
[PMID 24084248] The GSTM1null (deletion) and MGMT84 rs12917 (Phe/Phe) haplotype are associated with bulky DNA adduct levels in human leukocytes
[PMID 24115240] TP53 rs1042522 SNP in salivary gland neoplasms
[PMID 24175836] P53 Arg72Pro and MDM2 SNP309 Polymorphisms Cooperate to Increase Lung Adenocarcinoma Risk in Chinese Female Non-smokers: A Case Control Study
[PMID 24316395] Common Genetic Variants in 53BP1 Associated with Non-small Cell Lung Cancer Risk in Han Chinese
[PMID 24324286] Investigation of genetic polymorphisms related to the outcome of radiotherapy for prostate cancer patients
[PMID 24326769] The association between polymorphism of P53 Codon72 Arg/Pro and hepatocellular carcinoma susceptibility: evidence from a meta-analysis of 15 studies with 3,704 cases
[PMID 24349246] The T309G MDM2 Gene Polymorphism Is a Novel Risk Factor for Proliferative Vitreoretinopathy
[PMID 24369748] TP53 genetic polymorphisms, interactions with lifestyle factors and lung cancer risk: a case control study in a Chinese population
[PMID 24370206] Risk genes in head and neck cancer: A systematic review and meta-analysis of last 5years
[PMID 22773013] Genetic variants in TP53 and MDM2 associated with male infertility in Chinese population.
[PMID 22892830] Role of p53 codon 72 polymorphism in chromosomal aberrations and mitotic index in patients with chronic hepatitis B.
[PMID 23124483] Correlation of telomere length shortening with TP53 somatic mutations, polymorphisms and allelic loss in breast tumors and esophageal cancer.
[PMID 23125046] TP53*P72 allele influences negatively female life expectancy in a population of central Italy: cross-sectional study and genetic-demographic approach analysis.
[PMID 23311506] The association of a variant in the cell cycle control gene CCND1 and obesity on the development of asthma in the Swiss SAPALDIA study.
[PMID 23423487] Effect of TP53 codon 72 and MDM2 SNP309 polymorphisms on survival of gastric cancer among patients who receiving 5-fluorouracil-based postoperative adjuvant chemotherapy.
[PMID 23729685] Genotype misclassification in genetic association studies of the rs1042522 TP53 (Arg72Pro) polymorphism: a systematic review of studies of breast, lung, colorectal, ovarian, and endometrial cancer.
[PMID 24818791] Genetic Variation in the TP53 Pathway and Bladder Cancer Risk. A Comprehensive Analysis
[PMID 24863946] No evidence of correlation between p53 codon 72 G > C gene polymorphism and cancer risk in Indian population: a meta-analysis
[PMID 24935583] Association of the rs1042522 Polymorphism with Increased Risk of Prostate Adenocarcinoma in the Pakistani Population and its HuGE Review
[PMID 25479941] Genetic association of single nucleotide polymorphisms in P53 pathway with gastric cancer risk in a Chinese Han population
[PMID 25693086] The relationship of TP53 and GRIN2B gene polymorphisms with risk of occurrence and progression of primary open-angle glaucoma in a Polish population
[PMID 25734904] Impact of TP53 Codon 72 and MDM2 SNP 309 Polymorphisms in Pancreatic Ductal Adenocarcinoma
[PMID 26305668] The Relationship between Vascular Endothelial Growth Factor 1154G/A Polymorphism and Recurrent Implantation Failure
[PMID 26451011] Systematic meta-analyses and field synopsis of genetic association studies in colorectal adenomas
[PMID 25316267] TP53 and MDM2 polymorphisms and the risk of endometrial cancer in postmenopausal women
[PMID 27248495] Study of Association between Pre-Senile Cataracts and the Polymorphisms rs2228000 in XPC and rs1042522 in p53 in Spanish Population.
[PMID 27436625] The Arg72 variant of the p53 functional polymorphism (rs1042522) is associated with coronary artery disease in young South Africans of Indian ancestry.