Editing P53 (section)

== Gene ==
In humans, the ''TP53'' gene is located on the short arm of [[chromosome 17 (human)|chromosome 17]] (17p13.1).<ref name="pmid6396087" /><ref name="pmid3456488" /><ref name="pmid2047879" /><ref name="pmid 3001719" /> The gene spans 20 [[Kilo-base pair|kb]], with a non-coding [[exon]] 1 and a very long first [[Intron|intron]] of 10 kb, overlapping the [[Hp53int1]] gene. The coding sequence contains five regions showing a high degree of conservation in vertebrates, predominantly in exons 2, 5, 6, 7 and 8, but the sequences found in invertebrates show only distant resemblance to mammalian TP53.<ref name="pmid10618702">{{cite journal | vauthors = May P, May E | title = Twenty years of p53 research: structural and functional aspects of the p53 protein | journal = Oncogene | volume = 18 | issue = 53 | pages = 7621–36 | date = December 1999 | pmid = 10618702 | doi = 10.1038/sj.onc.1203285 | doi-access = free }}</ref> ''TP53'' [[orthologs]]<ref name="OrthoMaM">{{cite web | title = OrthoMaM phylogenetic marker: TP53 coding sequence | url = http://www.orthomam.univ-montp2.fr/orthomam/data/cds/detailMarkers/ENSG00000141510_TP53.xml | access-date = 2009-12-02 | archive-url = https://web.archive.org/web/20180317110251/http://www.orthomam.univ-montp2.fr/orthomam/data/cds/detailMarkers/ENSG00000141510_TP53.xml | archive-date = 2018-03-17 | url-status = dead }}</ref> have been identified in most [[mammals]] for which complete genome data are available. Elephants, with 20 genes for TP53, rarely get cancer.<ref>{{cite journal | vauthors = Sulak M, Fong L, Mika K, Chigurupati S, Yon L, Mongan NP, Emes RD, Lynch VJ | title = <i>TP53</i> copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants | journal = eLife | volume = 5 | date = September 2016 | pmid = 27642012 | doi = 10.7554/eLife.11994 | doi-access = free | pmc = 5061548 }}</ref>

In humans, a common [[polymorphism (biology)|polymorphism]] involves the substitution of an [[arginine]] for a [[proline]] at [[codon]] position 72 of exon 4. Many studies have investigated a genetic link between this variation and cancer susceptibility; however, the results have been controversial. For instance, a meta-analysis from 2009 failed to show a link for cervical cancer.<ref name="pmid19625214">{{cite journal | vauthors = Klug SJ, Ressing M, Koenig J, Abba MC, Agorastos T, Brenna SM, Ciotti M, Das BR, Del Mistro A, Dybikowska A, Giuliano AR, Gudleviciene Z, Gyllensten U, Haws AL, Helland A, Herrington CS, Hildesheim A, Humbey O, Jee SH, Kim JW, Madeleine MM, Menczer J, Ngan HY, Nishikawa A, Niwa Y, Pegoraro R, Pillai MR, Ranzani G, Rezza G, Rosenthal AN, Roychoudhury S, Saranath D, Schmitt VM, Sengupta S, Settheetham-Ishida W, Shirasawa H, Snijders PJ, Stoler MH, Suárez-Rincón AE, Szarka K, Tachezy R, Ueda M, van der Zee AG, von Knebel Doeberitz M, Wu MT, Yamashita T, Zehbe I, Blettner M | title = TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies | journal = The Lancet. Oncology | volume = 10 | issue = 8 | pages = 772–84 | date = August 2009 | pmid = 19625214 | doi = 10.1016/S1470-2045(09)70187-1 }}</ref> A 2011 study found that the ''TP53'' proline mutation did have a profound effect on pancreatic cancer risk among males.<ref name="pmid21468597">{{cite journal | vauthors = Sonoyama T, Sakai A, Mita Y, Yasuda Y, Kawamoto H, Yagi T, Yoshioka M, Mimura T, Nakachi K, Ouchida M, Yamamoto K, Shimizu K | title = TP53 codon 72 polymorphism is associated with pancreatic cancer risk in males, smokers and drinkers | journal = Molecular Medicine Reports | volume = 4 | issue = 3 | pages = 489–95 | year = 2011 | pmid = 21468597 | doi = 10.3892/mmr.2011.449 | doi-access = free }}</ref> A study of Arab women found that proline homozygosity at ''TP53'' codon 72 is associated with a decreased risk for breast cancer.<ref name="pmid20443084">{{cite journal | vauthors = Alawadi S, Ghabreau L, Alsaleh M, Abdulaziz Z, Rafeek M, Akil N, Alkhalaf M | title = P53 gene polymorphisms and breast cancer risk in Arab women | journal = Medical Oncology | volume = 28 | issue = 3 | pages = 709–15 | date = September 2011 | pmid = 20443084 | doi = 10.1007/s12032-010-9505-4 | s2cid = 207372095 }}</ref> One study suggested that ''TP53'' codon 72 polymorphisms, [[MDM2 SNP309]], and [[A2164G]] may collectively be associated with non-oropharyngeal cancer susceptibility and that MDM2 SNP309 in combination with ''TP53'' codon 72 may accelerate the development of non-oropharyngeal cancer in women.<ref name="pmid21656578">{{cite journal | vauthors = Yu H, Huang YJ, Liu Z, Wang LE, Li G, Sturgis EM, Johnson DG, Wei Q | title = Effects of MDM2 promoter polymorphisms and p53 codon 72 polymorphism on risk and age at onset of squamous cell carcinoma of the head and neck | journal = Molecular Carcinogenesis | volume = 50 | issue = 9 | pages = 697–706 | date = September 2011 | pmid = 21656578 | pmc = 3142329 | doi = 10.1002/mc.20806 }}</ref> A 2011 study found that ''TP53'' codon 72 polymorphism was associated with an increased risk of lung cancer.<ref name="pmid21316118">{{cite journal | vauthors = Piao JM, Kim HN, Song HR, Kweon SS, Choi JS, Yun WJ, Kim YC, Oh IJ, Kim KS, Shin MH | title = p53 codon 72 polymorphism and the risk of lung cancer in a Korean population | journal = Lung Cancer | volume = 73 | issue = 3 | pages = 264–7 | date = September 2011 | pmid = 21316118 | doi = 10.1016/j.lungcan.2010.12.017 }}</ref>

Meta-analyses from 2011 found no significant associations between ''TP53'' codon 72 polymorphisms and both colorectal cancer risk<ref name="pmid21140221">{{cite journal | vauthors = Wang JJ, Zheng Y, Sun L, Wang L, Yu PB, Dong JH, Zhang L, Xu J, Shi W, Ren YC | title = TP53 codon 72 polymorphism and colorectal cancer susceptibility: a meta-analysis | journal = Molecular Biology Reports | volume = 38 | issue = 8 | pages = 4847–53 | date = November 2011 | pmid = 21140221 | doi = 10.1007/s11033-010-0619-8 | s2cid = 11730631 }}</ref> and endometrial cancer risk.<ref name="pmid20552298">{{cite journal | vauthors = Jiang DK, Yao L, Ren WH, Wang WZ, Peng B, Yu L | title = TP53 Arg72Pro polymorphism and endometrial cancer risk: a meta-analysis | journal = Medical Oncology | volume = 28 | issue = 4 | pages = 1129–35 | date = December 2011 | pmid = 20552298 | doi = 10.1007/s12032-010-9597-x | s2cid = 32990396 }}</ref> A 2011 study of a Brazilian birth cohort found an association between the non-mutant arginine ''TP53'' and individuals without a family history of cancer.<ref name="pmid22116280">{{cite journal | vauthors = Thurow HS, Haack R, Hartwig FP, Oliveira IO, Dellagostin OA, Gigante DP, Horta BL, Collares T, Seixas FK | title = TP53 gene polymorphism: importance to cancer, ethnicity and birth weight in a Brazilian cohort | journal = Journal of Biosciences | volume = 36 | issue = 5 | pages = 823–31 | date = December 2011 | pmid = 22116280 | doi = 10.1007/s12038-011-9147-5 | s2cid = 23027087 }}</ref> Another 2011 study found that the p53 homozygous (Pro/Pro) genotype was associated with a significantly increased risk for renal cell carcinoma.<ref name="pmid21982800">{{cite journal | vauthors = Huang CY, Su CT, Chu JS, Huang SP, Pu YS, Yang HY, Chung CJ, Wu CC, Hsueh YM | title = The polymorphisms of P53 codon 72 and MDM2 SNP309 and renal cell carcinoma risk in a low arsenic exposure area | journal = Toxicology and Applied Pharmacology | volume = 257 | issue = 3 | pages = 349–55 | date = December 2011 | pmid = 21982800 | doi = 10.1016/j.taap.2011.09.018 | bibcode = 2011ToxAP.257..349H }}</ref>