Hereditary nonpolyposis colorectal cancer overview: Difference between revisions

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==Natural History, Complications and Prognosis==
==Natural History, Complications and Prognosis==


If left untreated, hereditary nonpolyposis colorectal cancer progression occurs rapidly and is then followed by centinel organ cancer or metastasis. Hereditary nonpolyposis colorectal cancer is an aggressive syndrome characterized by early onset of cancer. Commonly affected sites include endometrium (second most common after colon), [[ovary]], [[stomach]], [[small intestine]], [[hepatobiliary tract]], upper [[urinary tract]], [[brain]], and [[skin]]. Complications of hereditary nonpolyposis colorectal cancer are usually related to the surgery. The 5-year relative survival of patients with hereditary nonpolyposis colorectal cancer is approximately 79.3%.<ref name="pmid21205737">{{cite journal |vauthors=Hampel H, de la Chapelle A |title=The search for unaffected individuals with Lynch syndrome: do the ends justify the means? |journal=Cancer Prev Res (Phila) |volume=4 |issue=1 |pages=1–5 |year=2011 |pmid=21205737 |pmc=3076593 |doi=10.1158/1940-6207.CAPR-10-0345 |url=}}</ref> A feature associated with worse [[prognosis]] is the presence of metastasis at the time of diagnosis.<ref>Stigliano V, Assisi D, Cosimelli M, et al. Survival of hereditary non-polyposis colorectal cancer patients compared with sporadic colorectal cancer patients. J Exp Clin Cancer Res. 2008;27:39.</ref>
If left untreated, hereditary nonpolyposis colorectal cancer progression occurs rapidly and is then followed by centinel organ cancer or metastasis. Hereditary nonpolyposis colorectal cancer is an aggressive syndrome characterized by early onset of cancer. Commonly affected sites include endometrium (second most common after colon), [[ovary]], [[stomach]], [[small intestine]], [[hepatobiliary tract]], upper [[urinary tract]], [[brain]], and [[skin]]. Complications of hereditary nonpolyposis colorectal cancer are usually related to the surgery. The 5-year relative survival of patients with hereditary nonpolyposis colorectal cancer is approximately 79.3%.<ref name="pmid21205737">{{cite journal |vauthors=Hampel H, de la Chapelle A |title=The search for unaffected individuals with Lynch syndrome: do the ends justify the means? |journal=Cancer Prev Res (Phila) |volume=4 |issue=1 |pages=1–5 |year=2011 |pmid=21205737 |pmc=3076593 |doi=10.1158/1940-6207.CAPR-10-0345 |url=}}</ref> The presence of metastasis at the time of diagnosis is associated with a worse prognosis.<ref>Stigliano V, Assisi D, Cosimelli M, et al. Survival of hereditary non-polyposis colorectal cancer patients compared with sporadic colorectal cancer patients. J Exp Clin Cancer Res. 2008;27:39.</ref>


==Diagnosis==
==Diagnosis==

Revision as of 18:40, 6 February 2016

Hereditary Nonpolyposis Colorectal Cancer Microchapters

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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

Hereditary nonpolyposis colorectal cancer is an autosomal dominant genetic disease characterized by the early onset of colon cancer, endometrial cancer, and other malignant tumors caused by genetic mutations, that lead to an accumulation of DNA mismatches in the MMR gene. Hereditary nonpolyposis colorectal cancer is characterized by an increased risk of colorectal cancer and other cancers of the endometrium, ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin. Hereditary nonpolyposis colorectal cancer accounts for approximately 3-5% of colorectal cancer cases. Hereditary nonpolyposis colorectal canceris classified into 2 types: Lynch syndrome I (familial colon cancer) and Lynch syndrome II (other cancer of the gastrointestinal system or the reproductive system). Hereditary nonpolyposis colorectal canceris the most common hereditary colorectal carcinoma syndrome.[1] The increased risk for these cancers is due to inherited mutations that degrade the self-repair capability of DNA. The Amsterdam clinical criteria identifies candidates for genetic testing, and genetic testing can make a diagnosis of HPNCC. Surgery remains the mainstay therapy for Hereditary nonpolyposis colorectal cancer.[2]

Historical Perspective

Lynch syndrome was named in honor of Dr. Henry T. Lynch, an American physician and professor of medicine at Creighton University Medical Center in 1966.[3]

Classification

Hereditary nonpolyposis colorectal cancer may be classified into 2 types: Lynch syndrome I (familial colon cancer) and Lynch syndrome II (hereditary nonpolyposis colorectal cancer associated with other cancers of the gastrointestinal tract or reproductive system).[2] Other variants such as Muir-Torre syndrome and Turcot syndrome are considered subtypes of hereditary nonpolyposis colorectal cancer.[4]

Pathophysiology

Hereditary nonpolyposis colorectal cancer is an autosomal dominant genetic disease characterized by an early onset of colon cancer, endometrial cancer, and other malignant tumors.[5] Development of hereditary nonpolyposis colorectal cancer is the result of multiple genetic mutations. The most common genetic mutation involved in the pathogenesis of hereditary nonpolyposis colorectal cancer is a mutaiton in the MMR gene. Other genes involved in the pathogenesis of hereditary nonpolyposis colorectal cancer include: MSH-2, MLH-1, MSH-6, PMS-2 ,PMS-1, TGF-BR2, and MLH-3. This syndrome occurs most commonly in the proximal colon (60% to 80%) and endometrial cancer is the most common sentinel cancer among female patients with hereditary nonpolyposis colorectal cancer.[5]

Causes

Hereditary nonpolyposis colorectal cancer is caused by a genetic mutation in MMR gene, that results in defective repair of DNA sequence.[5]

Differentiating Hereditary nonpolyposis colorectal cancer from other Diseases

Hereditary nonpolyposis colorectal cancer must be differentiated from other diseases that cause familial colorectal cancer, such as: juvenile polyposis, familial adenomatous polyposis, Cowden syndrome, and MYH-associated polyposis.[6]

Epidemiology and Demographics

The prevalence of hereditary nonpolyposis colorectal cancer is approximately 2-7% of all diagnosed cases of colorectal cancer.[7] Hereditary nonpolyposis colorectal cancer commonly affects young adult population. The median age of diagnosis is between 40 to 45 years.[7] Hereditary nonpolyposis colorectal cancer affects men and women equally.[2] Hereditary nonpolyposis colorectal cancer usually affects individuals of the white race more commonly. Ethnically-diverse individuals are less likely to develop MMR mutations related with hereditary nonpolyposis colorectal cancer.[8]

Risk Factors

The most potent risk factor in the development of hereditary nonpolyposis colorectal cancer is gene mutations caused by defective DNA mismatch repair.[5]

Screening

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.[9][10]

Natural History, Complications and Prognosis

If left untreated, hereditary nonpolyposis colorectal cancer progression occurs rapidly and is then followed by centinel organ cancer or metastasis. Hereditary nonpolyposis colorectal cancer is an aggressive syndrome characterized by early onset of cancer. Commonly affected sites include endometrium (second most common after colon), ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin. Complications of hereditary nonpolyposis colorectal cancer are usually related to the surgery. The 5-year relative survival of patients with hereditary nonpolyposis colorectal cancer is approximately 79.3%.[10] The presence of metastasis at the time of diagnosis is associated with a worse prognosis.[11]

Diagnosis

Staging

There is no established system for the staging of hereditary nonpolyposis colorectal cancer.[2]

History and Symptoms

The hallmark of hereditary nonpolyposis colorectal cancer is a first-degree relative of those with known MMR/EPCAM gene mutation. A positive history of colorectal cancer and meeting Amsterdam I or II criteria or revised Bethesda guidelines is highly suggestive of hereditary nonpolyposis colorectal cancer. Some symptoms that are associated with colorectal cancer are change in bowel habits, hematochezia, and rectal pain.[12]

Physical Examination

Patients with hereditary nonpolyposis colorectal cancer usually appear healthy. Physical examination of patients with hereditary nonpolyposis colorectal cancermay show for the presence of the fordyce granules.[12]

Laboratory Findings

Laboratory findings consistent with the diagnosis of hereditary nonpolyposis colorectal cancer include the evaluation of genetic mutations, such as; germline testing for a deleterious mutation in the MMR (MLH1, MSH2, MSH6, and PMS2) or EPCAM gene. Other laboratory findings include: GCBC, Fecal occult blood (FOBT), serum CEA, CA 19-9 concentration, CA-125, serum iron concentrations, serum vitamin B12, folate concentrations, liver function tests, and pulmonary function tests.[13]

Chest X-Ray

There are no chest x-ray findings associated with hereditary nonpolyposis colorectal cancer.

CT Scan

There are no CT scan findings associated with hereditary nonpolyposis colorectal cancer.

MRI

There are no MRI findings associated with hereditary nonpolyposis colorectal cancer.

Other Diagnostic Studies

Diagnostic and screening endoscopy is recommended in the case of hereditary nonpolyposis colorectal cancer.[12] According to the American College of Gastroenterology, patients with hereditary nonpolyposis colorectal cancershould undergo colonoscopy every 2 years beginning at age 20–25 years, until age 40 years, then annually thereafter.[14]

Treatment

Medical Therapy

There is no medical treatment for hereditary nonpolyposis colorectal cancer.[1] However, hereditary nonpolyposis colorectal cancerpatients should consider diet optimization and pharmacological prevention.[5]

Surgery

Surgery is the mainstay of treatment for hereditary nonpolyposis colorectal cancer.[15] Surgical resection is recommended among patients with HPNCC because of the high rate of metachronous colorectal cancer. Subtotal colectomy with ileorectal anastomosis and postsurgical endoscopic rectal surveillance are advised when colorectal cancer develops in the setting of hereditary nonpolyposis colorectal cancer.

Primary Prevention

There is no established method for the primary prevention of hereditary nonpolyposis colorectal cancer.

Secondary Prevention

Effective measures for the secondary prevention of hereditary nonpolyposis colorectal cancer include: active surveillance, annual screening with genetic testing, colonoscopy, urine cytology, pelvic exam, and endometrial biopsy.[12][16]

Case Studies

Case #1

See also

References

  1. 1.0 1.1 Hendriks YM, de Jong AE, Morreau H, Tops CM, Vasen HF, Wijnen JT, Breuning MH, Bröcker-Vriends AH (2006). "Diagnostic approach and management of Lynch syndrome (hereditary nonpolyposis colorectal carcinoma): a guide for clinicians". CA Cancer J Clin. 56 (4): 213–25. PMID 16870997.
  2. 2.0 2.1 2.2 2.3 Hereditary nonpolyposis colorectal cancer. Wikipedia. https://en.wikipedia.org/wiki/Hereditary_nonpolyposis_colorectal_cancer Accessed on December 01, 2015
  3. Lynch HT, Lynch JF (1985). "Hereditary nonpolyposis colorectal cancer (Lynch syndromes I and II): a common genotype linked to oncogenes?". Med. Hypotheses. 18 (1): 19–28. PMID 4069033.
  4. Lynch HT, Lanspa S, Smyrk T, Boman B, Watson P, Lynch J (1991). "Hereditary nonpolyposis colorectal cancer (Lynch syndromes I & II). Genetics, pathology, natural history, and cancer control, Part I". Cancer Genet. Cytogenet. 53 (2): 143–60. PMID 1648437.
  5. 5.0 5.1 5.2 5.3 5.4 Si JW, Wang L, Ba XJ, Zhang X, Dong Y, Zhang JX, Li WT, Li T (2015). "[Clinicopathological screening of Lynch syndrome: a report of 2 cases and literature review]". Beijing Da Xue Xue Bao (in Chinese). 47 (5): 858–64. PMID 26474631.
  6. Kladny J, Lubinski J. Lynch syndrome (hereditary nonpolyposis colorectal cancer). Hered Cancer Clin Pract. 2008;6(2):99-102.
  7. 7.0 7.1 Aaltonen LA, Salovaara R, Kristo P, Canzian F, Hemminki A, Peltomäki P, Chadwick RB, Kääriäinen H, Eskelinen M, Järvinen H, Mecklin JP, de la Chapelle A (1998). "Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease". N. Engl. J. Med. 338 (21): 1481–7. doi:10.1056/NEJM199805213382101. PMID 9593786.
  8. Monteiro santos EM, Valentin MD, Carneiro F, et al. Predictive models for mutations in mismatch repair genes: implication for genetic counseling in developing countries. BMC Cancer. 2012;12:64.
  9. Vasen HF, Watson P, Mecklin JP, Lynch HT (Jun 1999). "New clinical criteria for hereditary nonpolyposis colorectal cancer (hereditary nonpolyposis colorectal cancer, Lynch syndrome) proposed by the International Collaborative group on hereditary nonpolyposis colorectal cancer". Gastroenterology. 116 (6): 1453–6. doi:10.1016/S0016-5085(99)70510-X. PMID 10348829.
  10. 10.0 10.1 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.
  11. Stigliano V, Assisi D, Cosimelli M, et al. Survival of hereditary non-polyposis colorectal cancer patients compared with sporadic colorectal cancer patients. J Exp Clin Cancer Res. 2008;27:39.
  12. 12.0 12.1 12.2 12.3 Kladny J, Lubinski J. Lynch syndrome (hereditary nonpolyposis colorectal cancer). hered Cancer Clin Pract. 2008;6(2):99-102.
  13. Lynch HT, Drescher K, Knezetic J, Lanspa S (2014). "Genetics, biomarkers, hereditary cancer syndrome diagnosis, heterogeneity and treatment: a review". Curr Treat Options Oncol. 15 (3): 429–42. doi:10.1007/s11864-014-0293-5. PMID 24827900.
  14. Rex DK, Johnson DA, Lieberman DA et al. Colorectal cancer prevention 2000: screening recommendations of the American College of Gastroenterology. Am J Gastroenterol 2000;95:868–77.
  15. Treatment of hereditary nonpolyposis colorectal cancer.Wikipedia.https://en.wikipedia.org/wiki/Hereditary_nonpolyposis_colorectal_cancer#Treatment Accessed on December 2, 2015
  16. Genetics of Colorectal Cancer–for health professionals (PDQ®). National Institute of Cancer 2015.http://www.cancer.gov/types/colorectal/hp/colorectal-genetics-pdq. Accessed on Novemeber 30, 2015


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