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Title: Jurnal Medical Aradean (Arad Medical Journal)
Abbreviated title: J. Med. Ar.
Publisher: "Vasile Goldis" University Press
Owner: Western University "Vasile Goldis" Arad, Romania
ISSN: 1224-3744
e-ISSN: 2067-7790

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SURGICAL AND MEDICAL MANAGEMENT OF HEREDITARY NON-POLYPOSIS COLO-RECTAL CANCER MANAGEMENT OF HNPCC PDF Print E-mail

SURGICAL AND MEDICAL MANAGEMENT OF HEREDITARY NON-POLYPOSIS COLO-RECTAL CANCER MANAGEMENT OF HNPCC

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Title:SURGICAL AND MEDICAL MANAGEMENT OF HEREDITARY NON-POLYPOSIS COLO-RECTAL CANCER MANAGEMENT OF HNPCC
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Article_Title:SURGICAL AND MEDICAL MANAGEMENT OF HEREDITARY NON-POLYPOSIS COLO-RECTAL CANCER
MANAGEMENT OF HNPCC
Authors:Carolina Negrei1, Corina Dalia Toderescu2*, Bianca Galateanu3, Cristian Balalau4, Miriana Stan1, Claudia Gutu1, Octav Ginghina5
Affiliation:1Department of Toxicology, “Carol Davila” University of Medicine and Pharmacy, 6, Traian Vuia Street, Bucharest, Romania
2 Department of Pharmaceutical Sciences, Faculty of Pharmacy, ”Vasile Goldis” Western University of Arad, 91-93, L. Rebreanu Street, Arad, Romania
3Department of Biochemistry and Molecular Biology, University of Bucharest, Bucharest, Romania
4“Sf. Pantelimon” Hospital Bucharest, Surgical Clinic, “Carol Davila” University of Medicine and Pharmacy, 340-342, Pantelimon Street, Bucharest, Romania
5“St. John Emergency Hospital” Bucharest, Surgical Clinic, “Carol Davila” University of Medicine and Pharmacy, 13, Vitan-Barzesti Street, Bucharest, Romania
Abstract:Hereditary non-polyposis colo-rectal cancer is an autosomal dominant disease and is described by markedly higher risk for colon and endometrial cancers. This disorder is characterised by loss of mismatch repair protein expression and DNA microsatellite instability. Clinical criteria (Amsterdam II) have served in identifying hereditary non-polyposis colo-rectal cancer families. To facilitate determination of colo-rectal tumours requiring molecular analysis, certain clinical criteria have been developed (Bethesda Guidelines). The recommendations for screening are for yearly/biennial colonoscopy and annual trans-vaginal ultrasound and endometrial sampling as early as 20 to 35 years of age. The management of this disorder, given the increased risk of developing endometrial and ovarian cancer, bilateral salpingoophorectomy and prophylactic hysterectomy should be presented to and discussed with HNPCC patients and also options for such patients’ management include completion colectomy and ileo-rectal anastomosis, monitoring or chemo-prevention, in case of colo-rectal cancer.
Keywords:colo-rectal cancer, endometrial cancer, colectomy, hysterectomy
References:Aaltonen LA, Peltomaki P, Mecklin JP et al., Replication errors in benign and malignant tumors from hereditary nonpolyposis colorectal cancer patients. Cancer Research 1994;54(7):1645–8
Aarnio M, Mecklin JP, Aaltonen LA, Nystrom-Lahti M, Jarvinen HJ, Life-time risk of different cancers in hereditary non-polyposis colorectal cancer (HNPCC) syndrome. International Journal of Cancer 1995;64(6):430–3
Aarnio M, Sankila R, Pukkala E et al., Cancer risk in mutation carriers of DNA-mismatch-repair genes. International Journal of Cancer 1999:81(2):214–218
Baba S., Hereditary nonpolyposis colorectal cancer: an update. Dis Colon Rectum 1997;40(10 Suppl):S86–S95
Baglietto L, Lindor NM, Dowty JG et al., Risks of Lynch syndrome cancers for MSH6 mutation carriers. J Natl Cancer Inst 2010;102(3):193–201
Baron JA, Beach M, Mandel JS, et al., Calcium Polyp Prevention Study Group. Calcium supplements for the prevention of colorectal adenomas. N Engl J Med 1999;340(2):101-7
Boks DES, Trujillo AP, Voogd AC, Morreau H, Kenter GG, Vasen HF., A Survival analysis of endometrial carcinoma associated with hereditary nonpolyposis colorectal cancer. International Journal of Cancer 2002;102(2):198–200
Bonadona V, Bonaiti B, Olschwang S et al., Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA 2011;305(22):2304–10
Box JC, Rodriguez-Bigas MA, Weber TK, Petrelli NJ., Clinical implications of multiple colorectal carcinomas in hereditary nonpolyposis colorectal carcinoma. Dis Colon Rectum 1999;42(6):717–21
Broaddus RR, Lynch HT, Chen LM et al., Pathologic features of endometrial carcinoma associated with HNPCC: a comparison with sporadic endometrial carcinoma. Cancer 2006;106(1):87–94
Burn J, Gerdes AM, Macrae F et al., Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet 2011;378(9809):2081–7
Chan TA., Nonsteroidal anti-inflammatory drugs, apoptosis, and colon-cancer chemoprevention. Lancet Oncol 2002;3(3):166-74
Cole BF, Baron JA, Sandler RS, et al., Folate Polyp Prevention Study Group. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA 2007;297(21):2351-9
De Jong AE, Morreau H, Van Puijenbroek M et al., The role of mismatch repair gene defects in the development of adenomas in patients with HNPCC. Gastroenterology 2004;126(1):42–8
De Vos tot Nederveen Cappel WH, Buskens E, van Duijvendijk P et al., Decision analysis in the surgical treatment of colorectal cancer due to a mismatch repair gene defect. Gut 2003;52(12):1752–5
De Vos tot Nederveen Cappel WH, Nagengast FM, Griffioen G, et al., Surveillance for hereditary nonpolyposis colorectal cancer: a long-term study on 114 families. Dis Colon Rectum 2002;45(12):1588–94
Dove-Edwin I, Boks D, Goff S et al., The outcome of endometrial carcinoma surveillance by ultrasound scan in women at risk of hereditary nonpolyposis colorectal carcinoma and familial colorectal carcinoma. Cancer 2002;94(6):1708–12
DuBois RN, Smalley WE., Cyclooxygenase, NSAIDs, and colorectal cancer. J Gastroenterol 1996;31(6):898-906
Dunlop MG, Farrington SM, Carothers AD et al., Cancer risk associated with germline DNA mismatch repair gene mutations. HumanMolecular Genetics 1997;6(1):105–110
Fitzgibbons RJ Jr, Lynch HT, StanislavGV et al., Recognition and treatment of patients with hereditary nonpolyposis colon cancer (Lynch syndromes I and II). Ann Surg 1987; 206(3):289–95
Gaglia P, Atkin WS, Whitelaw S et al., Variables associated with the risk of colorectal adenomas in asymptomatic patients with a family history of colorectal cancer. Gut 1995;36(3):385–90
Giovannucci E, Stampfer MJ, Colditz GA, et al., Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann Intern Med 1998;129(7):517-24
Grau MV, Baron JA, Sandler RS, et al., Vitamin D, calcium supplementation, and colorectal adenomas: results of a randomized trial. J Natl Cancer Inst 2003;95(23):1765-71
Haanstra JF, de Vos Tot Nederveen Cappel WH, Gopie JP et al., Quality of life after surgery for colon cancer in patients with Lynch syndrome: partial versus subtotal colectomy. Dis Colon Rectum 2012;55(6):3–659
Hendriks YMC, Wagner A, Morreau H et al., Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance. Gastroenterology 2004;127(1):17–25
Järvinen HJ, Aarnio M, Mustonen H et al., Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 2000;118(5);829–34
Jass JR., Colorectal adenomas in surgical specimens from subjects with hereditary non-polyposis colorectal cancer. Histopathology 1995;27(3):263–7
Jass JR, Smyrk TC, Stewart SM, Lane MR, Lanspa SJ, Lynch HT., Pathology of hereditary non-polyposis colorectal cancer. Anticancer Res 1994;14(4B):1631–4
Kalady MF, Lipman J, McGannon E, Church JM., Risk of colonic neoplasia after proctectomy for rectal cancer in hereditary nonpolyposis colorectal cancer. Ann Surg 2012;255(6):1121–25.
Kouri M, Laasonen A, Mecklin JP, Jarvinen H, Franssila K, Pyrhonen S., Diploid predominance in hereditary nonpolyposis colorectal carcinoma evaluated by flow cytometry. Cancer 1990;65(8):1825–9
Leenen CH, van Lier MG, van Doorn HC, van Leerdam ME, Kooi SG, de Waard J, Hoedemaeker RF, van den Ouweland AM, Hulspas SM, Dubbink HJ, Kuipers EJ, Wagner A, Dinjens WN, Steyerberg EW., Prospective evaluation of molecular screening for Lynch syndrome in patients with endometrial cancer </= 70 years. Gynecol Oncol 2012;125:414-420
Lanspa SJ, Jenkins JX, Cavalieri RJ et al., Surveillance in Lynch syndrome: how aggressive? Am J Gastroenterol 1994;89(11): 1978–80
Lanspa SJ, Lynch HT, Smyrk TC et al., Colorectal adenomas in the Lynch syndromes: results of a colonoscopy screening program. Gastroenterology 1990;98(5):1117–22
Laura R-S, Butzow R, Leminen A, Lehtovirtsa P, Mecklin JP, Järvinen HJ, Surveillance for endometrial cancer in hereditary nonplyposis colorectal cancer syndrome. International Journal of Cancer 2006; 120 (4):821–4
Lee JS, Petrelli NJ, Rodriguez-Bigas MA., Rectal cancer in hereditary nonpolyposis colorectal cancer. Am J Surg 2001;181(3): 207–10
Lindor NM, Petersen GM, Hadley DW et al., Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review. JAMA 2006;296(12):1507–17
Liu T, Wahlberg S, Burek E, Lindblom P, Rubio C, Lindblom A., Microsatellite instability as a predictor of a mutation in a DNA mismatch repair gene in familial colorectal cancer. Genes Chromosomes Cancer 2000;27:17-25
Lynch HT, de la Chapelle A., Hereditary colorectal cancer. New England Journal of Medicine 2003;348(10):919–932
Lynch HT, Smyrk TC, Watson P et al., Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. Gastroenterology 1993;104(5):1535–49
Madden MV, Neale KF, Nicholls RJ et al., Comparison of morbidity and function after colectomy with ileorectal anastomosis or restorative proctocolectomy for familial adenomatous polyposis. Br J Surg 1991;78(7):789–92
Maeda T, Cannom RR, Beart RW Jr, Etzioni DA., Decision model of segmental compared with total abdominal colectomy for colon cancer in hereditary nonpolyposis colorectal cancer. J Clin Oncol Off J Am Soc Clin Oncol 2010;28(7):1175–80
Marino M, Galuzzo P., Estrogen receptor! mediates the protective effects of estrogen in colon cancer Cancer Therapy 2008; 6:149-162
Markowitz SD., Aspirin and colon cancer--targeting prevention?. N Engl J Med. 2007;356(21):2195-8
Meagher AP, Farouk R, Dozois RR, Kelly KA, Pemberton JH J ileal pouch-anal anastomosis for chronic ulcerative colitis: complications and long-term outcome in 1310 patients. Br J Surg 1998;85(6):800–3
Mecklin JP, Aarnio M, Läärä E et al., Development of colorectal tumors in colonoscopic surveillance in Lynch Syndrome. Gastroenterology 2007;133(4):1093–1098
Mecklin JP, Jarvinen HJ, Clinical features of colorectal carcinoma in cancer family syndrome. Diseases of the Colon and Rectum 1986;29(3):160–164
Mecklin JP, Sipponen P, Jarvinen HJ, Histopathology of colorectal carcinomas and adenomas in cancer family syndrome. Diseases of the Colon and Rectum 1986;29(12):849–853
Moslein G, Nelson H, Thibodeau S, Dozois RR, Rectal carcinomas in HNPCC. Langenbecks Arch Chir Suppl Kongressbd 1998;115:1467–9
Moslein G, Tester DJ, Lindor NM, Honchel R, Cunningham JM, French AJ, Halling KC, Schwab M, Goretzki P, Thibodeau SN, Microsatellite instability and mutation analysis of hMSH2 and hMLH1 in patients with sporadic, familial and hereditary colorectal cancer. Hum Mol Genet 1996;5:1245-1252
Natarajan N, Watson P, Silva-Lopez E, Lynch HT, Comparison of extended colectomy and limited resection in patients with Lynch syndrome. Dis Colon Rectum 2010; 53(1):77–82
Nieminen TT, Gylling A, Abdel-Rahman WM et al., Molecular analysis of endometrial tumorigenesis: importance of complex hyperplasia regardless of atypia. Clinical Cancer Research 2009;15(18):5772–83
Obermair A,YouldenDR,Young JP et a., Risk of endometrial cancer for women diagnosed with HNPCC-related colorectal carcinoma. Int J Cancer 2010;127(11):2678–84
O'Shaughnessy JA, Kelloff GJ, Gordon GB, et al., Treatment and prevention of intraepithelial neoplasia: an important target for accelerated new agent development. Clin Cancer Res 2002;8(2):314-46
Parry S, Win AK, Parry B et al., Metachronous colorectal cancer risk for mismatch repair gene mutation carriers: the advantage of more extensive colon surgery. Gut 2011;60(7):950–7
Rijcken FE, Mourits MJ, Kleibeuker JH, Hollema H, van der Zee AG, Gynekologic screening in hereditary nonpolyposis colorectal cancer. Gynecologic Oncology 2003;91(1)74–80
Rodriguez-Bigas MA, Boland CR, Hamilton SR et al., A national cancer institute workshop on hereditary nonpolyposis colorectal cancer syndrome: meeting highlights and Bethesda guidelines. Journal of the National Cancer Institute 1997;89(23):1758–1762
Rodriguez-Bigas MA, Vasen HF, Pekka-Mecklin J et al., Rectal cancer risk in hereditary nonpolyposis colorectal cancer after abdominal colectomy. International collaborative group on HNPCC. Ann Surg 1997;225(2):202–7
Schmeler KM, Lynch HT, Chen LM et al., Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med 2006;354(3):261–9
Sinicrope FA, Half E, Morris JS, et al., for the Familial Adenomatous Polyposis Study Group. Cell proliferation and apoptotic indices predict adenoma regression in a placebo-controlled trial of celecoxib in familial adenomatous polyposis patients. Cancer Epidemiol Biomarkers Prev. Jun 2004;13(6):920-7
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Umar A, Boland CR, Terdiman JP, Syngal S, Chapelle Adl, Ruschoff J et al., Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch Syndrome) and microsatellite instability. J Natl Cancer Inst 2004;96:261-268
Vasen HFA, Mecklin JP, Meera Khan P, Lynch HT, The international collaborative group on hereditary nonpolyposis colorectal cancer (ICG-HNPCC). Diseases of the Colon and Rectum 1991;34(5):424–425
Vasen HFA, Möslein G, Alonso A et al., Guidelines for the clinical management of Lynch syndrome (hereditary nonpolyposis cancer). Journal of Medical Genetics 2007;44(6):353–62
Vasen HFA, Nagengast FM, Meera Khan P, Interval cancers in hereditary non-polyposis colorectal cancer (Lynch syndrome). The Lancet 1995;345(8958):1183–4
Vasen HFA, Offerhaus GJA, Den Hartog Jager FCA. et al., The tumour spectrum in hereditary non-polyposis colorectal cancer: a study of 24 kindreds in The Netherlands. International Journal of Cancer 1990;46(1):31–34
Vasen HFA, Watson P, Mecklin JP, Lynch HT, New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative Group on HNPCC. Gastroenterology 1999;116(6):1453–1456
Vasen HFA, Wijnen JT, Menko FH et al., Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterology 1996;110(4):1020–1027
Wu K, Willett WC, Fuchs CS, Colditz GA, Giovannucci EL, Calcium intake and risk of colon cancer in women and men. J Natl Cancer Inst 2002;94(6):437-46
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Correspondence:Corina Dalia Toderescu, ”Vasile Goldis” Western University of Arad, Faculty of Pharmacy, Department of Pharmaceutical Sciences, no. 91-93, L. Rebreanu Street, Arad, Romania, email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it
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Article Title:SURGICAL AND MEDICAL MANAGEMENT OF HEREDITARY NON-POLYPOSIS COLO-RECTAL CANCER
MANAGEMENT OF HNPCC
Authors:Carolina Negrei1, Corina Dalia Toderescu2*, Bianca Galateanu3, Cristian Balalau4, Miriana Stan1, Claudia Gutu1, Octav Ginghina5
Affiliation:1Department of Toxicology, “Carol Davila” University of Medicine and Pharmacy, 6, Traian Vuia Street, Bucharest, Romania
2 Department of Pharmaceutical Sciences, Faculty of Pharmacy, ”Vasile Goldis” Western University of Arad, 91-93, L. Rebreanu Street, Arad, Romania
3Department of Biochemistry and Molecular Biology, University of Bucharest, Bucharest, Romania
4“Sf. Pantelimon” Hospital Bucharest, Surgical Clinic, “Carol Davila” University of Medicine and Pharmacy, 340-342, Pantelimon Street, Bucharest, Romania
5“St. John Emergency Hospital” Bucharest, Surgical Clinic, “Carol Davila” University of Medicine and Pharmacy, 13, Vitan-Barzesti Street, Bucharest, Romania
Abstract:Hereditary non-polyposis colo-rectal cancer is an autosomal dominant disease and is described by markedly higher risk for colon and endometrial cancers. This disorder is characterised by loss of mismatch repair protein expression and DNA microsatellite instability. Clinical criteria (Amsterdam II) have served in identifying hereditary non-polyposis colo-rectal cancer families. To facilitate determination of colo-rectal tumours requiring molecular analysis, certain clinical criteria have been developed (Bethesda Guidelines). The recommendations for screening are for yearly/biennial colonoscopy and annual trans-vaginal ultrasound and endometrial sampling as early as 20 to 35 years of age. The management of this disorder, given the increased risk of developing endometrial and ovarian cancer, bilateral salpingoophorectomy and prophylactic hysterectomy should be presented to and discussed with HNPCC patients and also options for such patients’ management include completion colectomy and ileo-rectal anastomosis, monitoring or chemo-prevention, in case of colo-rectal cancer.
Keywords:colo-rectal cancer, endometrial cancer, colectomy, hysterectomy
References:Aaltonen LA, Peltomaki P, Mecklin JP et al., Replication errors in benign and malignant tumors from hereditary nonpolyposis colorectal cancer patients. Cancer Research 1994;54(7):1645–8
Aarnio M, Mecklin JP, Aaltonen LA, Nystrom-Lahti M, Jarvinen HJ, Life-time risk of different cancers in hereditary non-polyposis colorectal cancer (HNPCC) syndrome. International Journal of Cancer 1995;64(6):430–3
Aarnio M, Sankila R, Pukkala E et al., Cancer risk in mutation carriers of DNA-mismatch-repair genes. International Journal of Cancer 1999:81(2):214–218
Baba S., Hereditary nonpolyposis colorectal cancer: an update. Dis Colon Rectum 1997;40(10 Suppl):S86–S95
Baglietto L, Lindor NM, Dowty JG et al., Risks of Lynch syndrome cancers for MSH6 mutation carriers. J Natl Cancer Inst 2010;102(3):193–201
Baron JA, Beach M, Mandel JS, et al., Calcium Polyp Prevention Study Group. Calcium supplements for the prevention of colorectal adenomas. N Engl J Med 1999;340(2):101-7
Boks DES, Trujillo AP, Voogd AC, Morreau H, Kenter GG, Vasen HF., A Survival analysis of endometrial carcinoma associated with hereditary nonpolyposis colorectal cancer. International Journal of Cancer 2002;102(2):198–200
Bonadona V, Bonaiti B, Olschwang S et al., Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA 2011;305(22):2304–10
Box JC, Rodriguez-Bigas MA, Weber TK, Petrelli NJ., Clinical implications of multiple colorectal carcinomas in hereditary nonpolyposis colorectal carcinoma. Dis Colon Rectum 1999;42(6):717–21
Broaddus RR, Lynch HT, Chen LM et al., Pathologic features of endometrial carcinoma associated with HNPCC: a comparison with sporadic endometrial carcinoma. Cancer 2006;106(1):87–94
Burn J, Gerdes AM, Macrae F et al., Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet 2011;378(9809):2081–7
Chan TA., Nonsteroidal anti-inflammatory drugs, apoptosis, and colon-cancer chemoprevention. Lancet Oncol 2002;3(3):166-74
Cole BF, Baron JA, Sandler RS, et al., Folate Polyp Prevention Study Group. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA 2007;297(21):2351-9
De Jong AE, Morreau H, Van Puijenbroek M et al., The role of mismatch repair gene defects in the development of adenomas in patients with HNPCC. Gastroenterology 2004;126(1):42–8
De Vos tot Nederveen Cappel WH, Buskens E, van Duijvendijk P et al., Decision analysis in the surgical treatment of colorectal cancer due to a mismatch repair gene defect. Gut 2003;52(12):1752–5
De Vos tot Nederveen Cappel WH, Nagengast FM, Griffioen G, et al., Surveillance for hereditary nonpolyposis colorectal cancer: a long-term study on 114 families. Dis Colon Rectum 2002;45(12):1588–94
Dove-Edwin I, Boks D, Goff S et al., The outcome of endometrial carcinoma surveillance by ultrasound scan in women at risk of hereditary nonpolyposis colorectal carcinoma and familial colorectal carcinoma. Cancer 2002;94(6):1708–12
DuBois RN, Smalley WE., Cyclooxygenase, NSAIDs, and colorectal cancer. J Gastroenterol 1996;31(6):898-906
Dunlop MG, Farrington SM, Carothers AD et al., Cancer risk associated with germline DNA mismatch repair gene mutations. HumanMolecular Genetics 1997;6(1):105–110
Fitzgibbons RJ Jr, Lynch HT, StanislavGV et al., Recognition and treatment of patients with hereditary nonpolyposis colon cancer (Lynch syndromes I and II). Ann Surg 1987; 206(3):289–95
Gaglia P, Atkin WS, Whitelaw S et al., Variables associated with the risk of colorectal adenomas in asymptomatic patients with a family history of colorectal cancer. Gut 1995;36(3):385–90
Giovannucci E, Stampfer MJ, Colditz GA, et al., Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann Intern Med 1998;129(7):517-24
Grau MV, Baron JA, Sandler RS, et al., Vitamin D, calcium supplementation, and colorectal adenomas: results of a randomized trial. J Natl Cancer Inst 2003;95(23):1765-71
Haanstra JF, de Vos Tot Nederveen Cappel WH, Gopie JP et al., Quality of life after surgery for colon cancer in patients with Lynch syndrome: partial versus subtotal colectomy. Dis Colon Rectum 2012;55(6):3–659
Hendriks YMC, Wagner A, Morreau H et al., Cancer risk in hereditary nonpolyposis colorectal cancer due to MSH6 mutations: impact on counseling and surveillance. Gastroenterology 2004;127(1):17–25
Järvinen HJ, Aarnio M, Mustonen H et al., Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology 2000;118(5);829–34
Jass JR., Colorectal adenomas in surgical specimens from subjects with hereditary non-polyposis colorectal cancer. Histopathology 1995;27(3):263–7
Jass JR, Smyrk TC, Stewart SM, Lane MR, Lanspa SJ, Lynch HT., Pathology of hereditary non-polyposis colorectal cancer. Anticancer Res 1994;14(4B):1631–4
Kalady MF, Lipman J, McGannon E, Church JM., Risk of colonic neoplasia after proctectomy for rectal cancer in hereditary nonpolyposis colorectal cancer. Ann Surg 2012;255(6):1121–25.
Kouri M, Laasonen A, Mecklin JP, Jarvinen H, Franssila K, Pyrhonen S., Diploid predominance in hereditary nonpolyposis colorectal carcinoma evaluated by flow cytometry. Cancer 1990;65(8):1825–9
Leenen CH, van Lier MG, van Doorn HC, van Leerdam ME, Kooi SG, de Waard J, Hoedemaeker RF, van den Ouweland AM, Hulspas SM, Dubbink HJ, Kuipers EJ, Wagner A, Dinjens WN, Steyerberg EW., Prospective evaluation of molecular screening for Lynch syndrome in patients with endometrial cancer </= 70 years. Gynecol Oncol 2012;125:414-420
Lanspa SJ, Jenkins JX, Cavalieri RJ et al., Surveillance in Lynch syndrome: how aggressive? Am J Gastroenterol 1994;89(11): 1978–80
Lanspa SJ, Lynch HT, Smyrk TC et al., Colorectal adenomas in the Lynch syndromes: results of a colonoscopy screening program. Gastroenterology 1990;98(5):1117–22
Laura R-S, Butzow R, Leminen A, Lehtovirtsa P, Mecklin JP, Järvinen HJ, Surveillance for endometrial cancer in hereditary nonplyposis colorectal cancer syndrome. International Journal of Cancer 2006; 120 (4):821–4
Lee JS, Petrelli NJ, Rodriguez-Bigas MA., Rectal cancer in hereditary nonpolyposis colorectal cancer. Am J Surg 2001;181(3): 207–10
Lindor NM, Petersen GM, Hadley DW et al., Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review. JAMA 2006;296(12):1507–17
Liu T, Wahlberg S, Burek E, Lindblom P, Rubio C, Lindblom A., Microsatellite instability as a predictor of a mutation in a DNA mismatch repair gene in familial colorectal cancer. Genes Chromosomes Cancer 2000;27:17-25
Lynch HT, de la Chapelle A., Hereditary colorectal cancer. New England Journal of Medicine 2003;348(10):919–932
Lynch HT, Smyrk TC, Watson P et al., Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. Gastroenterology 1993;104(5):1535–49
Madden MV, Neale KF, Nicholls RJ et al., Comparison of morbidity and function after colectomy with ileorectal anastomosis or restorative proctocolectomy for familial adenomatous polyposis. Br J Surg 1991;78(7):789–92
Maeda T, Cannom RR, Beart RW Jr, Etzioni DA., Decision model of segmental compared with total abdominal colectomy for colon cancer in hereditary nonpolyposis colorectal cancer. J Clin Oncol Off J Am Soc Clin Oncol 2010;28(7):1175–80
Marino M, Galuzzo P., Estrogen receptor! mediates the protective effects of estrogen in colon cancer Cancer Therapy 2008; 6:149-162
Markowitz SD., Aspirin and colon cancer--targeting prevention?. N Engl J Med. 2007;356(21):2195-8
Meagher AP, Farouk R, Dozois RR, Kelly KA, Pemberton JH J ileal pouch-anal anastomosis for chronic ulcerative colitis: complications and long-term outcome in 1310 patients. Br J Surg 1998;85(6):800–3
Mecklin JP, Aarnio M, Läärä E et al., Development of colorectal tumors in colonoscopic surveillance in Lynch Syndrome. Gastroenterology 2007;133(4):1093–1098
Mecklin JP, Jarvinen HJ, Clinical features of colorectal carcinoma in cancer family syndrome. Diseases of the Colon and Rectum 1986;29(3):160–164
Mecklin JP, Sipponen P, Jarvinen HJ, Histopathology of colorectal carcinomas and adenomas in cancer family syndrome. Diseases of the Colon and Rectum 1986;29(12):849–853
Moslein G, Nelson H, Thibodeau S, Dozois RR, Rectal carcinomas in HNPCC. Langenbecks Arch Chir Suppl Kongressbd 1998;115:1467–9
Moslein G, Tester DJ, Lindor NM, Honchel R, Cunningham JM, French AJ, Halling KC, Schwab M, Goretzki P, Thibodeau SN, Microsatellite instability and mutation analysis of hMSH2 and hMLH1 in patients with sporadic, familial and hereditary colorectal cancer. Hum Mol Genet 1996;5:1245-1252
Natarajan N, Watson P, Silva-Lopez E, Lynch HT, Comparison of extended colectomy and limited resection in patients with Lynch syndrome. Dis Colon Rectum 2010; 53(1):77–82
Nieminen TT, Gylling A, Abdel-Rahman WM et al., Molecular analysis of endometrial tumorigenesis: importance of complex hyperplasia regardless of atypia. Clinical Cancer Research 2009;15(18):5772–83
Obermair A,YouldenDR,Young JP et a., Risk of endometrial cancer for women diagnosed with HNPCC-related colorectal carcinoma. Int J Cancer 2010;127(11):2678–84
O'Shaughnessy JA, Kelloff GJ, Gordon GB, et al., Treatment and prevention of intraepithelial neoplasia: an important target for accelerated new agent development. Clin Cancer Res 2002;8(2):314-46
Parry S, Win AK, Parry B et al., Metachronous colorectal cancer risk for mismatch repair gene mutation carriers: the advantage of more extensive colon surgery. Gut 2011;60(7):950–7
Rijcken FE, Mourits MJ, Kleibeuker JH, Hollema H, van der Zee AG, Gynekologic screening in hereditary nonpolyposis colorectal cancer. Gynecologic Oncology 2003;91(1)74–80
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*Correspondence:Corina Dalia Toderescu, ”Vasile Goldis” Western University of Arad, Faculty of Pharmacy, Department of Pharmaceutical Sciences, no. 91-93, L. Rebreanu Street, Arad, Romania, email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it