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{{Endometrial cancer}}
{{Endometrial cancer}}
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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.
 
 
==Overview==
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.


==Causes==
==Causes==
[[Genetic disorder]]s can also cause endometrial cancer. Overall, genetic causes contribute to 2–10% of endometrial cancer cases.  
Endometrial cancer arises following multiple genetic mutations. The following genes are involved in the development of endometrial cancer:
[[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%&nbsp;risk of developing endometrial cancer, higher than their risk of developing colorectal (bowel) or ovarian cancer.<ref name=Hoffman818/> Ovarian and endometrial cancer develop simultaneously in 20% of people. Endometrial cancer nearly always develops before colon cancer, on average, 11&nbsp;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 name=Hoffman818/> 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%.<ref name=Ma/><ref name=Colombo/> 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%.<ref name=Burke1/>
{| <!--Placing these in a table with no border will keep them together/aligned in any browser-->
|-
|
{| class="wikitable sortable"
|+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>
|-
!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 (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%
|}
|}


Women with a family history of endometrial cancer are at higher risk.<ref name=NCIBooklet/> Two genes most commonly associated with some other women's cancers, [[BRCA1]] and [[BRCA2]], do not cause endometrial cancer.<!--<ref name=Hoffman818/>--> There is an apparent link with these genes but it is attributable to the use of tamoxifen, a drug that itself can cause endometrial cancer, in breast and ovarian cancers.<ref name=Hoffman818/> The inherited genetic condition [[Cowden syndrome]] can also cause endometrial cancer. Women with this disorder have a 5–10%&nbsp;lifetime risk of developing endometrial cancer,<ref name="WCR2014Epi"/> compared to the 2–3%&nbsp;risk for unaffected women.<ref name=Ma/>
==References==
==References==
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{{reflist|2}}
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Latest revision as of 22:15, 26 November 2017

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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

  1. 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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