Hereditary nonpolyposis colorectal cancer screening
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]
Overview
According to the Bethesda guidelines and Amsterdam criteria, screening for hereditary nonpolyposis colorectal cancer by genetic testing is recommended among patients with family history or/and a confirmed diagnosis of colorectal cancer under age 50 years.[1][2]
Screening
- Genetic testing for mutations in DNA mismatch repair genes is expensive and time-consuming, so researchers have proposed techniques for identifying cancer patients who are most likely to be hereditary nonpolyposis colorectal carriers as ideal candidates for genetic testing.
- The Amsterdam Criteria are useful, but do not identify up to 30% of potential Lynch syndrome carriers.
- In the majority of patients with colorectal cancer, pathologists can measure microsatellite instability in colon tumor specimens, which is a surrogate marker for DNA mismatch repair gene dysfunction.[3][4]
- If there is microsatellite instability identified, there is a higher likelihood for a Lynch syndrome diagnosis.
- Recently, researchers combined microsatellite instability (MSI) profiling and immunohistochemistry testing for DNA mismatch repair gene expression and identified an extra 32% of Lynch syndrome carriers who would have been missed on MSI profiling alone.
- Currently, this combined immunohistochemistry and MSI profiling strategy is the most advanced way of identifying candidates for genetic testing for the Lynch syndrome. Genetic counseling and genetic testing are recommended for families that meet the Amsterdam criteria, preferably before the onset of colon cancer.[5]
- The Amsterdam criteria was initially used mainly in the research context to select kindred for genetic testing in order to identify the mutations involved. The Bethesda is slightly more clinically applicable. Both have been revised as more information has accumulated. The Amsterdam Criteria I and II identify patients for colonoscopic screening and approximately 40-80% of patients meet these criteria. On the other hand, the revised Bethesda criteria are used to identify patients for molecular screening of hereditary nonpolyposis colorectal cancer.
- Approximately 80% of patients are identified using the Bethesda criteria, although the specificity is low.[6][4]
Amsterdam Criteria
The following are the Amsterdam criteria in identifying high-risk candidates for molecular genetic testing:[1]
Amsterdam Criteria I:
- Three or more family members with a confirmed diagnosis of colorectal cancer, one of whom is a first degree (parent, child, sibling) relative of the other two
- Two successive affected generations
- One or more colon cancers diagnosed under age 50 years
- Familial adenomatous polyposis (FAP) has been excluded
Amsterdam Criteria II:
- Three or more family members with HNPCC-related cancers, one of whom is a first degree relative of the other two
- Two successive affected generations
- One or more of the HNPCC-related cancers diagnosed under age 50 years
- Familial adenomatous polyposis (FAP) has been excluded
Bethesda guidelines
The Revised Bethesda Guidelines are designed for identifying individuals at risk for HNPCC, and therefore recommend MSI testing.[7]
Revised Bethesda guidelines:
- Colorectal cancer diagnosed in a patient aged < 50 years.
- Presence of synchronous, metachronous colorectal or other Lynch syndrome‐related tumours, regardless of age.
- With MSI‐H phenotype diagnosed in a patient aged < 60 years.
- Patient with colorectal cancer and a first‐degree relative with a Lynch syndrome‐related tumor, with one of the cancers diagnosed at age <50 years.
- Patient with colorectal cancer with two or more first‐degree or second‐degree relatives with a Lynch syndrome‐related tumor, regardless of age.
- Lynch syndrome‐related tumors include colorectal, endometrial, stomach, ovarian, pancreas, ureter, renal pelvis, biliary tract and brain tumours, sebaceous gland adenomas and keratoacanthomas, and carcinoma of the small bowel.
Surveillance
- According to Netherlands Surveillance Protocol for Carriers of a MMR-Gene Mutation there is sufficient evidence to recommend routine screening for HNPCC-related cancers.[8][9]
- Recommended annual screening for patients with HNPCC (age 25 onwards or beginning no later than 5 years before the lowest age of onset in family) should include:[9]
- Physical examination
- Abdominal ultrasound
- Full colonoscopy
- Upper gastrointestinal endoscopy (age 35 onwards)
- Gynecological examination including transvaginal ultrasound
- Endometrial pipelle biopsy (age 35 onwards)
- Skin surveillance
- Urinalysis
References
- ↑ 1.0 1.1 Vasen HF, Watson P, Mecklin JP, Lynch HT (Jun 1999). "New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC". Gastroenterology. 116 (6): 1453–6. doi:10.1016/S0016-5085(99)70510-X. PMID 10348829.
- ↑ Hampel H, de la Chapelle A (2011). "The search for unaffected individuals with Lynch syndrome: do the ends justify the means?". Cancer Prev Res (Phila). 4 (1): 1–5. doi:10.1158/1940-6207.CAPR-10-0345. PMC 3076593. PMID 21205737.
- ↑ Lynch syndrome.Ganfyd.http://www.ganfyd.org/index.php?title=Lynch_syndrome Accessed on December 01, 2015
- ↑ 4.0 4.1 Vasen HF, Watson P, Mecklin JP, Lynch HT (1999). "New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC". Gastroenterology. 116 (6): 1453–6. PMID 10348829.
- ↑ Hereditary nonpolyposis colorectal cancer.Wikipedia.https://en.wikipedia.org/wiki/Hereditary_nonpolyposis_colorectal_cancer Accessed on December 2, 2015
- ↑ Lynch syndrome.Ganfyd.http://www.ganfyd.org/index.php?title=Lynch_syndrome Accessed on December 01, 2015
- ↑ Umar A, Boland CR, Terdiman JP, Syngal S, de la Chapelle A, Rüschoff J, Fishel R, Lindor NM, Burgart LJ, Hamelin R, Hamilton SR, Hiatt RA, Jass J, Lindblom A, Lynch HT, Peltomaki P, Ramsey SD, Rodriguez-Bigas MA, Vasen HF, Hawk ET, Barrett JC, Freedman AN, Srivastava S (2004). "Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability". J. Natl. Cancer Inst. 96 (4): 261–8. PMC 2933058. PMID 14970275.
- ↑ Vasen HF, Möslein G, Alonso A, Bernstein I, Bertario L, Blanco I, Burn J, Capella G, Engel C, Frayling I, Friedl W, Hes FJ, Hodgson S, Mecklin JP, Møller P, Nagengast F, Parc Y, Renkonen-Sinisalo L, Sampson JR, Stormorken A, Wijnen J (2007). "Guidelines for the clinical management of Lynch syndrome (hereditary non-polyposis cancer)". J. Med. Genet. 44 (6): 353–62. doi:10.1136/jmg.2007.048991. PMC 2740877. PMID 17327285.
- ↑ 9.0 9.1 Lindor NM, Petersen GM, Hadley DW, Kinney AY, Miesfeldt S, Lu KH, Lynch P, Burke W, Press N (2006). "Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review". JAMA. 296 (12): 1507–17. doi:10.1001/jama.296.12.1507. PMID 17003399.