TP53 P72R - GET-Evidence

Curation:
Currentness:

TP53 P72R

(TP53 Pro72Arg)


Short 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.

Variant evidence
Computational 3

Disruptive amino acid change (BLOSUM100 = 3), gene is associated with cancer.
PolyPhen-2 predicts TP53-P72R to be BENIGN with a score of 0.083 (sensitivity: 0.93; specificity: 0.85).

See unpublished research (below).

Functional 1

More susceptible to E6-mediated degradation

See Storey A et al. 1998 (9607760).

Case/Control

Mixed pathogenic and protective cancer reports.

See Storey A et al. 1998 (9607760), 15355915, Dahabreh IJ et al. 2010 (20615891).

Familial -
 
Clinical importance
Severity

Overall effect unclear.

Treatability

No treatment suggested.

Penetrance

Variable effects

 

Impact

Low clinical importance, Uncertain pathogenic

(The "low clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern

unknown

Summary of published research, and additional commentary

 

Allele frequency

  • C @ chr17:7579472: 62.8% (6752/10756) in EVS
  • C @ chr17:7520196: 52.5% (63/120) in GET-Evidence
  • Frequency shown in summary reports: 62.8% (6752/10756)

Publications
 

Ara S, Lee PS, Hansen MF, Saya H. Codon 72 polymorphism of the TP53 gene. Nucleic Acids Res. 1990 Aug 25;18(16):4961. PubMed PMID: 1975675; PubMed Central PMCID: PMC332028.

 

Storey A, Thomas M, Kalita A, Harwood C, Gardiol D, Mantovani F, Breuer J, Leigh IM, Matlashewski G, Banks L. Role of a p53 polymorphism in the development of human papillomavirus-associated cancer. Nature. 1998 May 21;393(6682):229-34. PubMed PMID: 9607760.

These authors report that this gene product for this variant is significantly more susceptible to E6-mediated degradation. Overrepresentation of the variant in tumor samples indicated that individuals homozygous for arginine 72 are about seven times more susceptible to HPV-associated tumorigenesis than heterozygotes.

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PubMed PMID: 15355915

Homozygous patients for Arg/Arg were significantly less likely to get colorectal cancer compared to heterozygous. Heterozygous had a 1.98x increased risk relative to homozygous.

Do TN, Ucisik-Akkaya E, Davis CF, Morrison BA, Dorak MT. TP53 R72P and MDM2 SNP309 polymorphisms in modification of childhood acute lymphoblastic leukemia susceptibility. Cancer Genet Cytogenet. 2009 Nov;195(1):31-6. PubMed PMID: 19837266.

 

Dahabreh IJ, Linardou H, Bouzika P, Varvarigou V, Murray S. TP53 Arg72Pro polymorphism and colorectal cancer risk: a systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev. 2010 Jul;19(7):1840-7. Review. PubMed PMID: 20615891.

 

Mustafina OE, Nasibullin TR, √Črdman VV, Tuktarova IA. [Association analysis of polymorphic loci of TP53 and NFKB1 genes with human age and longevity]. Adv Gerontol. 2011;24(3):397-404. Russian. PubMed PMID: 22184967.

 

Genomes
 

 

 

hu034DB1 - CGI sample GS00253-DNA_A02_200_37
hom C @ chr17:7579472

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

hu9385BA - CGI sample GS00253-DNA_E01_200_37
hom C @ chr17:7579472

 

 

 

 

huAE6220 - CGI sample GS00253-DNA_H01_200_37
het C @ chr17:7579472

 

 

huBEDA0B - CGI sample GS00253-DNA_C01_200_37
het C @ chr17:7579472

 

huC30901 - CGI sample GS00253-DNA_B01_200_37
hom C @ chr17:7579472

 

 

 

 

 

 

GS06985 - var-GS06985-1100-36-ASM
het C @ chr17:7520197

 

GS06994 - var-GS06994-1100-36-ASM
het C @ chr17:7520197

 

GS07357 - var-GS07357-1100-36-ASM
hom C @ chr17:7520197

 

GS10851 - var-GS10851-1100-36-ASM
hom C @ chr17:7520197

 

GS12004 - var-GS12004-1100-36-ASM
hom C @ chr17:7520197

 

GS18502 - var-GS18502-1100-36-ASM
hom C @ chr17:7520197

 

GS18526 - var-GS18526-1100-36-ASM
het C @ chr17:7520197

 

GS18537 - var-GS18537-1100-36-ASM
het C @ chr17:7520197

 

GS18558 - var-GS18558-1100-36-ASM
het C @ chr17:7520197

 

GS18942 - var-GS18942-1100-36-ASM
hom C @ chr17:7520197

 

GS18947 - var-GS18947-1100-36-ASM
hom C @ chr17:7520197

 

GS18956 - var-GS18956-1100-36-ASM
hom C @ chr17:7520197

 

GS19025 - var-GS19025-1100-36-ASM
het C @ chr17:7520197

 

GS19129 - var-GS19129-1100-36-ASM
het C @ chr17:7520197

 

GS19238 - var-GS19238-1100-36-ASM
het C @ chr17:7520197

 

GS19240 - var-GS19240-1100-36-ASM
het C @ chr17:7520197

 

GS19648 - var-GS19648-1100-36-ASM
het C @ chr17:7520197

 

GS19649 - var-GS19649-1100-36-ASM
hom C @ chr17:7520197

 

GS19669 - var-GS19669-1100-36-ASM
het C @ chr17:7520197

 

GS19670 - var-GS19670-1100-36-ASM
het C @ chr17:7520197

 

GS19701 - var-GS19701-1100-36-ASM
het C @ chr17:7520197

 

GS19703 - var-GS19703-1100-36-ASM
het C @ chr17:7520197

 

GS19735 - var-GS19735-1100-36-ASM
hom C @ chr17:7520197

 

GS19834 - var-GS19834-1100-36-ASM
het C @ chr17:7520197

 

GS20502 - var-GS20502-1100-36-ASM
hom C @ chr17:7520197

 

GS20509 - var-GS20509-1100-36-ASM
het C @ chr17:7520197

 

Other external references
 

    dbSNP
  • rs1042522
    www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi
    PharmGKB
  • [Precursor Cell Lymphoblastic Leukemia-Lymphoma]
    Risk or phenotype-associated allele: R72P non-wild type; unspecified; minor allele designation varies by ethnicity in dbSNP Phenotype: Childhood acute lymphoblastic leukemia (ALL) risk association with gene dosage effect (p = 0.002) resulting in a strong association of homozygous genotype (OR = 2.9) and no sex effect. Univariate analysis of disease association showed OR = 1.36 for heterozygote, OR = 3.31 for homozygous, versus homozygous wild type, in ALL, with P(trend) OR = 1.71, p = 0.002 using an additive model. Study size: 528. Study population/ethnicity: 114 cases childhood acute lymphoblastic leukemia (<=14 years) and 414 healthy newborn controls (1988 to 1999) from South Wales in the United Kingdom. Significance metric(s): p = 0.002, OR = 2.9 Type of association: CO
    www.ncbi.nlm.nih.gov/pubmed/19837266
  • [Colorectal Neoplasms; Neoplasms; Prostatic Neoplasms; Stomach Neoplasms]
    The p53 codon 72 polymorphism was found be associated with different cancers, like colorectal adenocarcinoma, gastric cancer, and prostate cancer.
    www.ncbi.nlm.nih.gov/pubmed/12824702; PubMed ID:17546594; PubMed ID:19339276
  • [Precursor Cell Lymphoblastic Leukemia-Lymphoma]
    Risk or phenotype-associated allele: combined alleles of TP53 rs1042522 (R72P), and DAXX rs2073524; both alleles unspecified; for both alleles, minor allele designation varies by ethnicity in dbSNP. Phenotype: There was suggestive evidence for interaction between DAXX rs2073524 and TP53 rs1042522 (R72P) alleles in risk of childhood ALL for homozygous genotypes (p = 0.05). Disease risk association with TP53 rs1042522 (R72P) increased in the presence of the DAXX rs2073524 variant allele (OR per allele = 1.49, p = 0.005). This interaction was female-specific (OR per allele = 2.41, p = 0.004), where the risk conferred by TP53 rs1042522 (R72P) homozygosity was greater for girls carrying the wild-type MDM2 genotype (OR = 7.1, p = 0.02). Study size: 528. Study population/ethnicity: 114 cases childhood acute lymphoblastic leukemia (< or = 14 years) and 414 healthy newborn controls (1988 to 1999) from South Wales in the United Kingdom. Significance metric(s): OR = (1.49 to 7.1), p = (0.004 to 0.05) Type of association: CO
    www.ncbi.nlm.nih.gov/pubmed/19837266
    PolyPhen-2
  • Score: 0.127 (benign)
    Web search results (149 hits -- see all)
  • Role of TP53 P72R polymorphism in human papillomavirus ...
    Role of TP53 P72R polymorphism in human papillomavirus associated premalignant laryngeal neoplasm ... Role of TP53 P72R polymorphism in human papillomavirus associated ...
    www.ncbi.nlm.nih.gov/pmc/articles/PMC1734865
  • TP53 [PharmGKB]
    TP53: c.215C>G; P72R; g.7176820G>C. Related Diseases: Neoplasms ... Asian gastric cancer patients with TP53:Arg72Pro, Pro/Pro genotype had shorter ...
    www.pharmgkb.org/do/serve?objId=PA36679&objCls=Gene
  • Carcinogenesis -- Sprague et al. 28 (8): 1680 Table BL1
    rs9894946. TP53-14. 21 226 bp 3' of STP C>T. rs1614984. TP53-11. IVS7+92T>G. rs12951053. TP53-10 ... IVS4-125T>C. rs9895829. TP53-01. Ex4+119C>G (P72R) rs1042522. TP53-34 ...
    carcin.oxfordjournals.org/cgi/content-nw/full/28/8/1680/TBL1
  • Genetic variation in TP53 and risk of breast cancer in a ...
    TP53-11. IVS7+92T>G. rs12951053. TP53-10. IVS7+72T>C. rs12947788. TP53-16 ... TP53-66. IVS4-91A>G. rs2909430. TP53-65. IVS4-125T>C. rs9895829. TP53-01. Ex4+119C>G (P72R) ...
    carcin.oxfordjournals.org/cgi/content/full/28/8/1680/TBL1
  • TP53 - SNPedia
    TP53 SNPs associated with increased risk for breast cancer include: ... known as P72R. Retrieved from "http://www.snpedia.com/index.php/TP53" Category: Is a ...
    www.snpedia.com/index.php/TP53
  • Identifying interacting SNPs using Monte Carlo logic regression
    the inclusion of TP53(P72R) d. and CD14. d. in the. model, the selection ... interaction between CD14, TP53(P72R), and the. CBS gene would appear to be a worthwhile ...
    biostat.jhsph.edu/~iruczins/publications/...
  • Author index
    Role of TP53 P72R polymorphism in human papillomavirus associated premalignant ... Role of TP53 P72R polymorphism in human papillomavirus associated premalignant ...
    jmg.bmj.com/content/38/5/by/author
  • Supplemental Table 1. Discovery SNPs* SNP Chromosome 17 ...
    T>C TP53. 6. rs1614984 7512177. 21226bp 3' of STP. C>T TP53. 7. rs12951053 ... P72R TP53. 11. rs1642785 7520526 IVS2+38C>G. TP53. 11. rs8079544 7520777 IVS1-112G>A. TP53. 10 ...
    cancerres.aacrjournals.org/cgi/data/.../DC1/3
  • Rs1042522 - SNPedia
    This SNP, a variant in the TP53 gene, is 1 of 25 SNPs reported to represent ... commonly called the Arg72 variant, although P72R and Arg72Pro are also common in the literature. ...
    www.snpedia.com/index.php/Rs1042522

Other in silico analyses
 

  • NBLOSUM100 score = 5
  • GET-Evidence autoscore = 4

Edit history
 

Gene search

"GENE" or "GENE A123C":

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