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| {{CMG}}{{AE}}{{MD}} | | {{CMG}}{{AE}}{{MD}} |
| ==Overview== | | ==Overview== |
| There are both genetic and environmental causes of endometrial carcinoma. Some of the genetic causes are hereditary nonpolyposis colon cancer (HNPCC) syndrome and cowden syndrome.The sporadic colorectal cancers develop from environmental causes.
| | 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== | | ==Causes== |
| 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>
| | Endometrial cancer arises following multiple genetic mutations. The following genes are involved in the development of endometrial cancer: |
| :* Lynch syndrome (Hereditary nonpolyposis colon cancer (HNPCC) syndrome)
| | {| <!--Placing these in a table with no border will keep them together/aligned in any browser--> |
| [[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.<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
| | | |
| 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> Cowden syndrome is associated with mutations in ''PTEN'', a tumor suppressor gene, that cause the ''PTEN'' protein not to work properly leading to hyperactivity of the mTOR pathway.
| | {| 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% |
| | |} |
| | |} |
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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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