Hereditary nonpolyposis colorectal cancer overview
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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 (HNPCC) 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. HNPCC accounts for approximately 3-5% of colorectal cancer cases. HNPCC is classified into 2 types; Lynch Syndrome I (familial colon cancer) and Lynch Syndrome II (other cancer of the gastrointestinal system or the reproductive system). HNPCC is 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 HNPCC.[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 (HNPCC associated with other cancers of the gastrointestinal tract or reproductive system).[4] Other variants such as Muir-Torre syndrome and Turcot syndrome are considered subtypes of HNPCC.[5]
Pathophysiology
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 MMR gene.[6] Development of HNPCC is the result of multiple genetic mutations. Genes involved in the pathogenesis of HNPCC include; MSH-2, MLH-1, MSH-6, PMS-2 ,PMS-1, TGF-BR2, and MLH-3. This syndrome occurs mostly in the proximal colon (60% to 80%) and endometrial cancer is the most common sentinel cancer among female patients with HNPCC.[6]
Causes
Hereditary nonpolyposis colorectal cancer is caused by a genetic mutation in MMR gene, that results in defective repair of DNA sequence.[6]
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 (FAP), Cowden syndrome, and MYH-associated polyposis.[7]
Epidemiology and demographics
The prevalence of hereditary nonpolyposis colorectal cancer is approximately 2-7% of all diagnosed cases of colorectal cancer.[8] HNPCC commonly affects young adult population. The median age of diagnosis is between 40 to 45 years.[8] Hereditary nonpolyposis colorectal cancer affects men and women equally.[4] HNPCC 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.[9]
Risk Factors
The most potent risk factor in the development of hereditary nonpolyposis colorectal cancer is gene mutations caused by defective DNA mismatch repair.[6]
Screening
According to the Bethesda guidelines and Amsterdam criteria, screening for HNPCC by genetic testing is recommended among patients with family history or/and a confirmed diagnosis of colorectal cancer under age 50 years.[10][11]
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. Common sites of affection include endometrium (second most common after colon), ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin. Complications of HNPCC are usually related to the surgery. The 5-year relative survival of patients with colorectal HNPCC cancer is approximately 79.3%. A feature associated with worse prognosis is late stage colorectal diagnosis or metastasis.[12]
Diagnosis
Staging
There is no established system for the staging of hereditary nonpolyposis colorectal cancer.[4]
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 HNPCC. Some symptoms that are associated with colorectal cancer are change in bowel habits, hematochezia, and rectal pain.[13]
Physical Examination
Patients with hereditary nonpolyposis colorectal cancer usually appear healthy. Physical examination of patients with HNPCC may show for the presence of the fordyce granules.[13]
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.[14]
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 HNPCC.[13] According to the American College of Gastroenterology, patients with HNPCC should undergo colonoscopy every 2 years beginning at age 20–25 years, until age 40 years, then annually thereafter.[15]
Treatment
Medical Therapy
There is no medical treatment for hereditary nonpolyposis colorectal cancer.[6][1] However, HNPCC patients should consider diet optimization and pharmacological prevention.
Surgery
Surgery is the mainstay of treatment for hereditary nonpolyposis colorectal cancer.[16] 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 HNPCC.
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.[13] [17]
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.
- ↑ 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.
- ↑ 4.0 4.1 4.2 Hereditary nonpolyposis colorectal cancer. Wikipedia. https://en.wikipedia.org/wiki/Hereditary_nonpolyposis_colorectal_cancer Accessed on December 01, 2015
- ↑ 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.
- ↑ 6.0 6.1 6.2 6.3 6.4 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 (HNPCC). Hered Cancer Clin Pract. 2008;6(2):99-102.
- ↑ 8.0 8.1 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.
- ↑ 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.
- ↑ 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.
- ↑ 13.0 13.1 13.2 13.3 Kladny J, Lubinski J. Lynch syndrome (HNPCC). 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.
- ↑ 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