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| __NOTOC__ | | __NOTOC__ |
| {{Endometrial cancer}} | | {{Endometrial cancer}} |
| {{CMG}} | | {{CMG}}{{AE}}{{MD}} |
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| ==Overview== | | ==Overview== |
| The cause of endometrial cancer has not been identified.
| | Causes of endometrial cancer include genetic mutations of the ''[[KRAS]]'' gene, ''[[TP53]]'' gene, ''[[P16 (gene)|TP16]]'' gene, and/or ''[[PTEN]]'' gene. Other genetic mutations have also been described. |
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| | | ==Causes== |
| ==Overview== | | Endometrial cancer arises following multiple genetic mutations. The following genes are involved in the development of endometrial cancer: |
| There are both genetic and environmental causes of endometrial carcinoma. Some of the genetic causes are Hereditary nonpolyposis colon cancer (HNPCC) syndrome.The sporadic colorectal cancers develop from environmental causes.
| | {| <!--Placing these in a table with no border will keep them together/aligned in any browser--> |
| | | |- |
| ==Causes==
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| Overall, genetic causes contribute to 2–10% of endometrial cancer cases.<ref name="pmid24098868">{{cite journal| author=Reinbolt RE, Hays JL| title=The Role of PARP Inhibitors in the Treatment of Gynecologic Malignancies. | journal=Front Oncol | year= 2013 | volume= 3 | issue= | pages= 237 | pmid=24098868 | doi=10.3389/fonc.2013.00237 | pmc=PMC3787651 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24098868 }} </ref>
| | {| class="wikitable sortable" |
| :* Lynch syndrome
| | |+Mutations found in Type I and Type II endometrial cancers<ref>International Agency for Research on Cancer (2014). World Cancer Report 2014. World Health Organization. Chapter 5.12. ISBN 978-92-832-0429-9.</ref> |
| [[Lynch syndrome]], an [[autosomal dominant]] genetic disorder that mainly causes [[colorectal cancer]], also causes endometrial cancer, especially before menopause. Women with Lynch syndrome have a 40–60% risk of developing endometrial cancer, higher than their risk of developing colorectal (bowel) or ovarian cancer.<ref>{{cite book | last = Hoffman | first = Barbara | title = Williams gynecology | publisher = McGraw-Hill Medical | location = New York | year = 2012 | isbn = 9780071716727. }}</ref> Ovarian and endometrial cancer develop simultaneously in 20% of people. Endometrial cancer nearly always develops before colon cancer, on average, 11 years before.<ref name=Ma>{{cite journal |last1=Ma |first1=J |last2=Ledbetter |first2=N |last3=Glenn |first3=L |year=2013 |title=Testing women with endometrial cancer for lynch syndrome: should we test all? |journal=Journal of the Advanced Practitioner in Oncology |volume=4 |issue=5 |pages=322–30 |doi= |pmid=25032011 |pmc=4093445}}</ref> [[Carcinogenesis]] in Lynch syndrome comes from a mutation in ''[[MLH1]]'' and/or ''MLH2'': genes that participate in the process of [[mismatch repair]], which allows a cell to correct mistakes in the DNA.<ref>{{cite book | last = Hoffman | first = Barbara | title = Williams gynecology | publisher = McGraw-Hill Medical | location = New York | year = 2012 | isbn = 9780071716727. }}</ref> Other genes mutated in Lynch syndrome include ''[[MSH2]]'', ''[[MSH6]]'', and ''[[PMS2]]'', which are also mismatch repair genes. Women with Lynch syndrome represent 2–3% of endometrial cancer cases; some sources place this as high as 5%. Depending on the gene mutation, women with Lynch syndrome have different risks of endometrial cancer. With ''[[MLH1]]'' mutations, the risk is 54%; with ''[[MSH2]]'', 21%; and with [[MSH6]], 16%. | | |- |
| :* Cowden syndrome
| | !Gene mutated |
| Women with a family history of endometrial cancer are at higher risk. The inherited genetic condition [[Cowden syndrome]] can also cause endometrial cancer. Women with this disorder have a 5–10% lifetime risk of developing endometrial cancer, compared to the 2–3% risk for unaffected women..<ref>Kumar (2009). Robbins and Cotran Pathologic Basis of DiseaseProfessional Edition, 8th ed. Saunders, An Imprint of Elsevier.</ref><ref>{{cite book | last = Cotran | first = Robbins | title = Pathologic Basis of Disease | publisher = Saunders//Elsevier | location = Jacksonville, FL, U.S.A | year = 2009 | isbn = 978-1-4160-3121-5 }}</ref>
| | !Mutation type |
| | !Type I prevalence |
| | !Type II prevalence |
| | |- |
| | |''[[ARID1A]]'' |
| | |[[point mutation]] |
| | |40% |
| | |unknown |
| | |- |
| | | ''CTNNB1'' |
| | |point mutation |
| | |14–44% |
| | |unknown |
| | |- |
| | |''[[FGFR2]]'' |
| | |point mutation |
| | |16% |
| | |unknown |
| | |- |
| | |''[[KRAS]]'' |
| | |point mutation |
| | |10–20% |
| | |unknown |
| | |- |
| | | ''PIK3R1'' |
| | |point mutation |
| | |43% |
| | |unknown |
| | |- |
| | |''[[TP53]]'' |
| | |point mutation |
| | |10–20% |
| | |90% |
| | |- |
| | |''[[PTEN (gene)|PTEN]]'' |
| | |point mutation |
| | |37–61% |
| | |unknown |
| | |- |
| | |''[[MLH1]]'' |
| | |[[gene silencing|epigenetic silencing]] |
| | |30% |
| | |unknown |
| | |- |
| | | ''RASSF1A'' |
| | |epigenetic silencing |
| | |48% |
| | |unknown |
| | |- |
| | | ''SPRY2'' |
| | |epigenetic silencing |
| | |20% |
| | |unknown |
| | |- |
| | | ''PPP2R1A'' |
| | |point mutation |
| | |unknown |
| | |17–41% |
| | |- |
| | | ''CDH1 (gene)|CDH1'' |
| | |[[loss of heterozygosity]] |
| | |unknown |
| | |80–90% |
| | |- |
| | |''[[p16 (gene)|CDKN2A]]'' |
| | |loss of heterozygosity and/or<br />epigenetic silencing |
| | |20% |
| | |40% |
| | |- |
| | | ''PIK3CA'' ([[oncogene]]) |
| | |point mutation or amplification (molecular biology)|amplification |
| | |24–39% |
| | |20–30% |
| | |- |
| | | ''PIK3R1'' (oncogene) |
| | |point mutation |
| | |unknown |
| | |12% |
| | |- |
| | | ''STK15'' (oncogene) |
| | |amplification |
| | |unknown |
| | |60% |
| | |- |
| | |''[[CCNE1]]'' (oncogene) |
| | |amplification |
| | |unknown |
| | |55% |
| | |- |
| | | ''ERBB2'' (oncogene) |
| | |amplification |
| | |unknown |
| | |30% |
| | |- |
| | |''[[CCND1]]'' (oncogene) |
| | |amplification |
| | |unknown |
| | |26% |
| | |} |
| | |} |
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| ==References== | | ==References== |
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| {{WikiDoc Help Menu}} | | {{WikiDoc Help Menu}} |
| {{WikiDoc Sources}} | | {{WikiDoc Sources}} |
| | [[Category:Up-To-Date]] |
| | [[Category:Oncology]] |
| | [[Category:Medicine]] |
| | [[Category:Gynecology]] |
| | [[Category:Surgery]] |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Monalisa Dmello, M.B,B.S., M.D. [2]
Overview
Causes of endometrial cancer include genetic mutations of the KRAS gene, TP53 gene, TP16 gene, and/or PTEN gene. Other genetic mutations have also been described.
Causes
Endometrial cancer arises following multiple genetic mutations. The following genes are involved in the development of endometrial cancer:
Mutations found in Type I and Type II endometrial cancers[1]
| Gene mutated
|
Mutation type
|
Type I prevalence
|
Type II prevalence
|
| ARID1A
|
point mutation
|
40%
|
unknown
|
| CTNNB1
|
point mutation
|
14–44%
|
unknown
|
| FGFR2
|
point mutation
|
16%
|
unknown
|
| KRAS
|
point mutation
|
10–20%
|
unknown
|
| PIK3R1
|
point mutation
|
43%
|
unknown
|
| TP53
|
point mutation
|
10–20%
|
90%
|
| PTEN
|
point mutation
|
37–61%
|
unknown
|
| MLH1
|
epigenetic silencing
|
30%
|
unknown
|
| RASSF1A
|
epigenetic silencing
|
48%
|
unknown
|
| SPRY2
|
epigenetic silencing
|
20%
|
unknown
|
| PPP2R1A
|
point mutation
|
unknown
|
17–41%
|
| CDH1
|
loss of heterozygosity
|
unknown
|
80–90%
|
| CDKN2A
|
loss of heterozygosity and/or
epigenetic silencing
|
20%
|
40%
|
| PIK3CA (oncogene)
|
amplification
|
24–39%
|
20–30%
|
| PIK3R1 (oncogene)
|
point mutation
|
unknown
|
12%
|
| STK15 (oncogene)
|
amplification
|
unknown
|
60%
|
| CCNE1 (oncogene)
|
amplification
|
unknown
|
55%
|
| ERBB2 (oncogene)
|
amplification
|
unknown
|
30%
|
| CCND1 (oncogene)
|
amplification
|
unknown
|
26%
|
|
References
- ↑ International Agency for Research on Cancer (2014). World Cancer Report 2014. World Health Organization. Chapter 5.12. ISBN 978-92-832-0429-9.
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