Hereditary nonpolyposis colorectal cancer overview: Difference between revisions
| Line 73: | Line 73: | ||
===Medical Therapy=== | ===Medical Therapy=== | ||
There is no medical treatment for hereditary nonpolyposis colorectal cancer.<ref name="pmid16870997">{{cite journal |vauthors=Hendriks YM, de Jong AE, Morreau H, Tops CM, Vasen HF, Wijnen JT, Breuning MH, Bröcker-Vriends AH |title=Diagnostic approach and management of Lynch syndrome (hereditary nonpolyposis colorectal carcinoma): a guide for clinicians |journal=CA Cancer J Clin |volume=56 |issue=4 |pages=213–25 |year=2006 |pmid=16870997 |doi= |url=}}</ref> However, hereditary nonpolyposis colorectal | There is no medical treatment for hereditary nonpolyposis colorectal cancer.<ref name="pmid16870997">{{cite journal |vauthors=Hendriks YM, de Jong AE, Morreau H, Tops CM, Vasen HF, Wijnen JT, Breuning MH, Bröcker-Vriends AH |title=Diagnostic approach and management of Lynch syndrome (hereditary nonpolyposis colorectal carcinoma): a guide for clinicians |journal=CA Cancer J Clin |volume=56 |issue=4 |pages=213–25 |year=2006 |pmid=16870997 |doi= |url=}}</ref> However, hereditary nonpolyposis colorectal cancer patients should consider diet optimization and pharmacological prevention.<ref name="pmid26474631">{{cite journal |vauthors=Si JW, Wang L, Ba XJ, Zhang X, Dong Y, Zhang JX, Li WT, Li T |title=[Clinicopathological screening of Lynch syndrome: a report of 2 cases and literature review] |language=Chinese |journal=Beijing Da Xue Xue Bao |volume=47 |issue=5 |pages=858–64 |year=2015 |pmid=26474631 |doi= |url=}}</ref> | ||
===Surgery=== | ===Surgery=== | ||
Revision as of 21:39, 9 February 2016
|
Hereditary Nonpolyposis Colorectal Cancer Microchapters |
|
Differentiating Hereditary Nonpolyposis Colorectal Cancer from other Diseases |
|---|
|
Diagnosis |
|
Treatment |
|
Case Studies |
|
Hereditary nonpolyposis colorectal cancer overview On the Web |
|
American Roentgen Ray Society Images of Hereditary nonpolyposis colorectal cancer overview |
|
Hereditary nonpolyposis colorectal cancer overview in the news |
|
Directions to Hospitals Treating Hereditary nonpolyposis colorectal cancer |
|
Risk calculators and risk factors for Hereditary nonpolyposis colorectal cancer overview |
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 (also known as Lynch syndrome or HNPCC) 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 first described by Dr. Henry T. Lynch, an American physician, 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 mutation 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%). 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 distant 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. Common symptoms of hereditary nonpolyposis colorectal cancer include constipation, hematochezia, and rectal pain.[12]
Physical Examination
Patients with hereditary nonpolyposis colorectal cancer usually appear healthy. Physical examination of patients with hereditary nonpolyposis colorectal cancer may show for the presence of the fordyce granules.[12]
Laboratory Findings
Laboratory findings consistent with the diagnosis of hereditary nonpolyposis colorectal cancer, may include: positive germline testing for hereditary nonpolyposis colorectal cancer genes (MLH1, MSH2, MSH6, and PMS2), positive EPCAM gene testing, and elevated serum concentration of CEA and CA 125.[13]
Chest X-Ray
There are no chest x-ray findings associated with hereditary nonpolyposis colorectal cancer.
CT Scan
There are no characteristic CT findings in hereditary nonpolyposis colorectal cancer.[14] In some cases, CT findings associated with hereditary nonpolyposis colorectal cancer may include: detection of extracolonic lesions, diffuse polyposis is characteristically absent, and findings consistent with colorectal cancer, usually right-sided.
MRI
There are no characteristic MRI findings associated with hereditary nonpolyposis colorectal cancer.[14] In some cases, findings associated with hereditary nonpolyposis colorectal cancer, may include: visualization of tumor depth into rectal wall (useful for pre-operative assessment) and lymph node involvement.[15]
Other Diagnostic Studies
Diagnostic and screening endoscopy are recommended in the case of hereditary nonpolyposis colorectal cancer.[12] According to the American College of Gastroenterology, patients with hereditary nonpolyposis colorectal cancer should undergo colonoscopy every 2 years beginning at age 20–25 years, until age 40 years, then annually thereafter.[16]
Treatment
Medical Therapy
There is no medical treatment for hereditary nonpolyposis colorectal cancer.[1] However, hereditary nonpolyposis colorectal cancer patients should consider diet optimization and pharmacological prevention.[5]
Surgery
Surgery is the mainstay of treatment for hereditary nonpolyposis colorectal cancer.[17] Surgical resection is recommended among patients with hereditary nonpolyposis colorectal cancer because of the high rate of metachronous colorectal cancer. Subtotal colectomy with ileorectal anastomosis and post-surgical 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][18]
Case Studies
See also
References
- ↑ 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.
- ↑ 2.0 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
- ↑ 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.
- ↑ 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.
- ↑ 5.0 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.
- ↑ Kladny J, Lubinski J. Lynch syndrome (hereditary nonpolyposis colorectal cancer). Hered Cancer Clin Pract. 2008;6(2):99-102.
- ↑ 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.
- ↑ 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.<nowiki>
- ↑ 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.
- ↑ 10.0 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.
- ↑ 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.
- ↑ 12.0 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.
- ↑ 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.
- ↑ 14.0 14.1 Hereditary nonpolyposis colorectal cancer. Dr Amir Rezaee and Dr Frank Gaillard et al. Radiopaedia 2015. http://radiopaedia.org/articles/hereditary-non-polyposis-colorectal-cancer-1. Accessed on December 02, 2015
- ↑ Medina and Blackmore, Evidence-Based Imaging: Optimizing Imaging in Patient Care. Chapter 5: Imaging based screening for colorectal cancer. Springer 2005.
- ↑ 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.
- ↑ Treatment of hereditary nonpolyposis colorectal cancer.Wikipedia.https://en.wikipedia.org/wiki/Hereditary_nonpolyposis_colorectal_cancer#Treatment Accessed on December 2, 2015
- ↑ 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