Familial Cancer

, Volume 12, Issue 2, pp 341–345 | Cite as

Lynch syndrome: the patients perspective

Original Article

Abstract

People with Lynch syndrome have a high lifetime risk for the development of colorectal, endometrial and several other types of cancer. Lynch syndrome is caused by germline mutations in genes encoding DNA mismatch repair proteins. In this review, issues that concern Lynch patients are highlighted from the patients’ perspective. Both authors are affected by Lynch syndrome and are active in Lynch patient organizations. The goal of this review is to assist heath care providers in the improvement of care for individuals who share our disorder. Institutional and/or national guidelines that should lead to the identification of Lynch patients have been developed in many countries. However, adherence to these guidelines is poor and the consequence is severe underdiagnosis of Lynch syndrome. An important task of patient organizations is therefore to increase awareness of Lynch syndrome among the general public and health care providers. Because diagnosis of Lynch syndrome based on family history is difficult, the use of molecular and or histological techniques that permit unequivocal diagnosis should be more aggressively promoted. Since Lynch syndrome encompasses a broad spectrum of cancers, a multidisciplinary treatment and screening protocol for all Lynch patients is necessary. Lynch patients must be seen by a team of specialists that are knowledgeable in the various manifestations of Lynch syndrome. Because tumors with mismatch repair deficiency have specific properties, identification of effective chemotherapy regimens, specifically targeted to patients with deficiencies in DNA repair mechanisms, must be developed. The high lifetime risk of developing cancer in Lynch patients warrants lifestyle advice and research into chemopreventive measures that reduce the risk of cancer in this vulnerable group. Implementation of these recommendations will result in greatly improved quality of life for people affected with Lynch syndrome, it is therefore important that health care providers and patient organizations work together to achieve these goals.

Keywords

Lynch syndrome DNA mismatch repair deficiency Patients rights 

References

  1. 1.
    Lynch HT, Lynch PM, Lanspa SJ, Snyder CL, Lynch JF, Boland CR (2009) Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clin Genet 76:1–18PubMedCrossRefGoogle Scholar
  2. 2.
    Bonadona V, Bonaiti B, Olschwang S, Grandjouan S, Huiart L, Longy M, Guimbaud R, Buecher B, Bignon YJ, Caron O, Colas C, Nogues C, Lejeune-Dumoulin S, Olivier-Faivre L, Polycarpe-Osaer F, Nguyen TD, Desseigne F, Saurin JC, Berthet P, Leroux D, Duffour J, Manouvrier S, Frebourg T, Sobol H, Lasset C, Bonaiti-Pellie C (2011) Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA 305:2304–2310PubMedCrossRefGoogle Scholar
  3. 3.
    Poulogiannis G, Frayling IM, Arends MJ (2010) DNA mismatch repair deficiency in sporadic colorectal cancer and Lynch syndrome. Histopathology 56:167–179PubMedCrossRefGoogle Scholar
  4. 4.
    Vasen HF, Abdirahman M, Brohet R, Langers AM, Kleibeuker JH, Kouwen M, Koornstra JJ, Boot H, Cats A, Dekker E, Sanduleanu S, Poley JW, Hardwick JC, Vos Tot Nederveen Cappel WH, van der Meulen-de Jong AE, Tan TG, Jacobs MA, Mohamed FL, de Boer SY, van de Meeberg PC, Verhulst ML, Salemans JM, van, Bentem N, Westerveld BD, Vecht J, Nagengast FM (2010) One to 2-year surveillance intervals reduce risk of colorectal cancer in families with Lynch syndrome Gastroenterology 138: 2300–2306Google Scholar
  5. 5.
    de Jong AE, Hendriks YM, Kleibeuker JH, de Boer SY, Cats A, Griffioen G, Nagengast FM, Nelis FG, Rookus MA, Vasen HF (2006) Decrease in mortality in Lynch syndrome families because of surveillance. Gastroenterology 130:665–671PubMedCrossRefGoogle Scholar
  6. 6.
    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) 4:1–5CrossRefGoogle Scholar
  7. 7.
    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 296:1507–1517PubMedCrossRefGoogle Scholar
  8. 8.
    Hampel H, Frankel WL, Martin E, Arnold M, Khanduja K, Kuebler P, Nakagawa H, Sotamaa K, Prior TW, Westman J, Panescu J, Fix D, Lockman J, Comeras I, de la Chapelle A (2005) Screening for the Lynch syndrome (hereditary nonpolyposis colorectal cancer). N Engl J Med 352:1851–1860PubMedCrossRefGoogle Scholar
  9. 9.
    Singh H, Schiesser R, Anand G, Richardson PA, El-Serag HB (2010) Underdiagnosis of Lynch syndrome involves more than family history criteria. Clin Gastroenterol Hepatol 8:523–529PubMedCrossRefGoogle Scholar
  10. 10.
    Wang G, Kuppermann M, Kim B, Phillips KA, Ladabaum U (2012) Influence of patient preferences on the cost-effectiveness of screening for lynch syndrome. J Oncol Pract 8:e24s–e30sPubMedCrossRefGoogle Scholar
  11. 11.
    Dinh TA, Rosner BI, Atwood JC, Boland CR, Syngal S, Vasen HF, Gruber SB, Burt RW (2011) Health benefits and cost-effectiveness of primary genetic screening for Lynch syndrome in the general population. Cancer Prev Res (Phila) 4:9–22CrossRefGoogle Scholar
  12. 12.
    Ladabaum U, Wang G, Terdiman J, Blanco A, Kuppermann M, Boland CR, Ford J, Elkin E, Phillips KA (2011) Strategies to identify the Lynch syndrome among patients with colorectal cancer: a cost-effectiveness analysis. Ann Intern Med 155:69–79PubMedCrossRefGoogle Scholar
  13. 13.
    Vasen HF, Moslein G, Alonso A, Aretz S, Bernstein I, Bertario L, Blanco I, Bulow S, Burn J, Capella G, Colas C, Engel C, Frayling I, Rahner N, Hes FJ, Hodgson S, Mecklin JP, Moller P, Myrhoj T, Nagengast FM, Parc Y, Ponz de Leon M, Renkonen-Sinisalo L, Sampson JR, Stormorken A, Tejpar S, Thomas HJ, Wijnen J, Lubinski J, Jarvinen H, Claes E, Heinimann K, Karagiannis JA, Lindblom A, Dove-Edwin I, Muller H (2010) Recommendations to improve identification of hereditary and familial colorectal cancer in Europe. Fam Cancer 9:109–115PubMedCrossRefGoogle Scholar
  14. 14.
    Bonnet D, Selves J, Toulas C, Danjoux M, Duffas JP, Portier G, Kirzin S, Ghouti L, Carrere N, Suc B, Alric L, Barange K, Buscail L, Chaubard T, Imani K, Guimbaud R (2012) Simplified identification of Lynch syndrome: a prospective, multicenter study. Dig Liver Dis 44:515–522PubMedCrossRefGoogle Scholar
  15. 15.
    Auranen A, Joutsiniemi T (2011) A systematic review of gynecological cancer surveillance in women belonging to hereditary nonpolyposis colorectal cancer (Lynch syndrome) families. Acta Obstet Gynecol Scand 90:437–444PubMedCrossRefGoogle Scholar
  16. 16.
    Sargent DJ, Marsoni S, Monges G, Thibodeau SN, Labianca R, Hamilton SR, French AJ, Kabat B, Foster NR, Torri V, Ribic C, Grothey A, Moore M, Zaniboni A, Seitz JF, Sinicrope F, Gallinger S (2010) Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol 28:3219–3226PubMedCrossRefGoogle Scholar
  17. 17.
    Dorard C, de Thonel A, Collura A, Marisa L, Svrcek M, Lagrange A, Jego G, Wanherdrick K, Joly AL, Buhard O, Gobbo J, Penard-Lacronique V, Zouali H, Tubacher E, Kirzin S, Selves J, Milano G, Etienne-Grimaldi MC, Bengrine-Lefevre L, Louvet C, Tournigand C, Lefevre JH, Parc Y, Tiret E, Flejou JF, Gaub MP, Garrido C, Duval A (2011) Expression of a mutant HSP110 sensitizes colorectal cancer cells to chemotherapy and improves disease prognosis. Nat Med 17:1283–1289PubMedCrossRefGoogle Scholar
  18. 18.
    Kolonel LN, Altshuler D, Henderson BE (2004) The multiethnic cohort study: exploring genes, lifestyle and cancer risk. Nat Rev Cancer 4:519–527PubMedCrossRefGoogle Scholar
  19. 19.
    Diergaarde B, Braam H, Vasen HF, Nagengast FM, van Muijen GN, Kok FJ, Kampman E (2007) Environmental factors and colorectal tumor risk in individuals with hereditary nonpolyposis colorectal cancer. Clin Gastroenterol Hepatol 5:736–742PubMedCrossRefGoogle Scholar
  20. 20.
    Botma A, Nagengast FM, Braem MG, Hendriks JC, Kleibeuker JH, Vasen HF, Kampman E (2010) Body mass index increases risk of colorectal adenomas in men with Lynch syndrome: the GEOLynch cohort study. J Clin Oncol 28:4346–4353PubMedCrossRefGoogle Scholar
  21. 21.
    Burn J, Gerdes AM, Macrae F, Mecklin JP, Moeslein G, Olschwang S, Eccles D, Evans DG, Maher ER, Bertario L, Bisgaard ML, Dunlop MG, Ho JW, Hodgson SV, Lindblom A, Lubinski J, Morrison PJ, Murday V, Ramesar R, Side L, Scott RJ, Thomas HJ, Vasen HF, Barker G, Crawford G, Elliott F, Movahedi M, Pylvanainen K, Wijnen JT, Fodde R, Lynch HT, Mathers JC, Bishop DT (2011) Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet 378:2081–2087PubMedCrossRefGoogle Scholar
  22. 22.
    Mueck AO, Seeger H, Rabe T (2010) Hormonal contraception and risk of endometrial cancer: a systematic review. Endocr Relat Cancer 17:R263–R271PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Vereniging HNPCC-LynchUtrechtThe Netherlands
  2. 2.Lynch Syndrome InternationalVacavilleUSA
  3. 3.Academic Medical CenterTytgat Institute for Liver and Intestinal ResearchAmsterdamThe Netherlands

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