Familial Cancer

, Volume 9, Issue 4, pp 563–570 | Cite as

Frequency of extracolonic tumors in Brazilian families with Lynch syndrome: analysis of a hereditary colorectal cancer institutional registry

  • Felipe Carneiro da Silva
  • Ligia Petrolini de Oliveira
  • Érika Monteiro Santos
  • Wilson Toshihiko Nakagawa
  • Samuel Aguiar Junior
  • Mev Dominguez Valentin
  • Benedito Mauro Rossi
  • Fábio de Oliveira Ferreira
Article

Abstract

Lynch syndrome (LS) is caused by inherited germline mutations in mismatch repair (MMR) genes. It is one of the commonest forms of inherited predisposition to colorectal cancer (CRC), accounting for 2–5% of all CRC. LS is characterized by early age of onset, with a tendency for multiplicity and an increased risk for extra-colonic tumors at particular sites. In this study we have evaluated the frequency of extra-colonic tumors in 60 unrelated LS families fulfilling the Amsterdam criteria (ACI. ACII) from the Oncotree database of the Hereditary Colorectal Cancer Registry of the AC Camargo Hospital. All families’ pedigree was extensively analyzed, varying from 2 to 6 generations with a total of 2,095 individuals evaluated. As expected, colorectal cancer was the most frequent tumor in the families (334 cases). We found 200 extracolonic tumors among all individuals with a higher ratio in women (123 cases) than men (77 cases). By far, breast cancer (32 cases) was the most frequent extracolonic manifestation in women followed by endometrial (20 cases) and uterine cervix cancer (20 cases). For man, prostate (16 cases) and stomach (12 cases) cancer were the most frequent extracolonic tumors. It is well know that establishing the diagnosis is challenging and requires knowledge and surveillance. Thus, recognition of individuals and families with hereditary predisposition to cancer according to clinical and molecular features, combined with intensive surveillance and management programs, can contribute substantially to improve results related to the diagnosis and characterization of LS.

Keywords

CRC Extracolonic tumors Familial cancer HNPCC LS 

Abbreviations

HNPCC

Hereditary non-polyposis colorectal cancer

CRC

Colorectal cancer

MMR

Mismatch repair gene

LS

Lynch syndrome

ACI

Amsterdam criteria I

ACII

Amsterdam criteria II

Notes

Acknowledgment

Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

References

  1. 1.
    Woolf CM (1958) A genetic study of carcinoma of the large intestine. Am J Hum Genet 10(1):42–47PubMedGoogle Scholar
  2. 2.
    Lovett E (1976) Family studies in cancer of the colon and rectum. Br J Surg 63(1):13–18CrossRefPubMedGoogle Scholar
  3. 3.
    Macklin MT (1960) Inheritance of cancer of the stomach and large intestine in man. J Natl Cancer Inst 24:551–571PubMedGoogle Scholar
  4. 4.
    Duncan JL, Kyle J (1982) Family incidence of carcinoma of the colon and rectum in north-east Scotland. Gut 23(2):169–171CrossRefPubMedGoogle Scholar
  5. 5.
    Potter JD (1999) Colorectal cancer: molecules and populations. J Natl Cancer Inst 91(11):916–932CrossRefPubMedGoogle Scholar
  6. 6.
    Warthin AS (1913) Heredity with reference to carcinoma as shown by the study of the cases examined in the pathological laboratory of the University of Michigan. Arch Int Med 12:546–555Google Scholar
  7. 7.
    Savage D (1956) A family history of uterine and gastro-intestinal cancer. Br Med J 2(4988):341–343CrossRefPubMedGoogle Scholar
  8. 8.
    Kluge T (1964) Familial cancer of the colon. Acta Chir Scand 127:392–398PubMedGoogle Scholar
  9. 9.
    Lynch HT, Krush AJ (1971) Cancer family “G” revisited: 1895–1970. Cancer 27(6):1505–1511CrossRefPubMedGoogle Scholar
  10. 10.
    Boland CR, Troncale FJ (1984) Familial colonic cancer without antecedent polyposis. Ann Intern Med 100(5):700–701PubMedGoogle Scholar
  11. 11.
    Ministry of Health/National Institute of Cancer-Inca (2010) Available from: http://www1.inca.gov.br/estimativa/2010/index.asp?link=tabelaestados.asp&UF=BR. Cited 1 May 2010
  12. 12.
    Geary J, Sasieni P, Houlston R et al (2008) Gene-related cancer spectrum in families with hereditary non-polyposis colorectal cancer (HNPCC). Fam Cancer 7(2):163–172CrossRefPubMedGoogle Scholar
  13. 13.
    Lynch HT, Ens J, Lynch JF, Watson P (1988) Tumor variation in three extended Lynch syndrome II kindreds. Am J Gastroenterol 83(7):741–747PubMedGoogle Scholar
  14. 14.
    Lynch HT, Lynch JF (1993) The Lynch syndromes. Curr Opin Oncol 5(4):687–696CrossRefPubMedGoogle Scholar
  15. 15.
    Lin KM, Shashidharan M, Ternent CA et al (1998) Colorectal and extracolonic cancer variations in MLH1/MSH2 hereditary non-polyposis colorectal cancer kindreds and the general population. Dis Colon Rectum 41(4):428–433CrossRefPubMedGoogle Scholar
  16. 16.
    Watson P, Riley B (2005) The tumor spectrum in the Lynch syndrome. Fam Cancer 4(3):245–248CrossRefPubMedGoogle Scholar
  17. 17.
    Vasen HF, Mecklin JP, Khan PM, Lynch HT (1991) The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer (ICG-HNPCC). Dis Colon Rectum 34(5):424–425CrossRefPubMedGoogle Scholar
  18. 18.
    Vasen HF, Watson P, Mecklin JP, Lynch HT (1999) New clinical criteria for hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology 116(6):1453–1456CrossRefPubMedGoogle Scholar
  19. 19.
    Lynch HT, Smyrk TC, Watson P et al (1993) Genetics, natural history, tumor spectrum, and pathology of hereditary non-polyposis colorectal cancer: an updated review. Gastroenterology 104(5):1535–1549PubMedGoogle Scholar
  20. 20.
    Marra G, Boland CR (1995) Hereditary non-polyposis colorectal cancer: the syndrome, the genes, and historical perspectives. J Natl Cancer Inst 87(15):1114–1125CrossRefPubMedGoogle Scholar
  21. 21.
    Lynch HT, Smyrk T (1996) Hereditary non-polyposis colorectal cancer (Lynch syndrome): an updated review. Cancer 78(6):1149–1167CrossRefPubMedGoogle Scholar
  22. 22.
    Lynch HT, Smyrk T, Lynch J (1997) An update of HNPCC (Lynch syndrome). Cancer Genet Cytogenet 93(1):84–99CrossRefPubMedGoogle Scholar
  23. 23.
    Peltomäki P, Vasen HF (1997) Mutations predisposing to hereditary non-polyposis colorectal cancer: database and results of a collaborative study. The International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer. Gastroenterology 113(4):1146–1158CrossRefPubMedGoogle Scholar
  24. 24.
    Giardiello FM (1997) Genetic testing in hereditary colorectal cancer. JAMA 278(15):1278–1281CrossRefPubMedGoogle Scholar
  25. 25.
    Bai YQ, Akiyama Y, Nagasaki H et al (1999) Predominant germ-line mutation of the hMSH2 gene in Japanese hereditary non-polyposis colorectal cancer kindreds. Int J Cancer 82(4):512–515CrossRefPubMedGoogle Scholar
  26. 26.
    Kim JC, Kim HC, Roh SA et al (2001) hMLH1 and hMSH2 mutations in families with familial clustering of gastric cancer and hereditary non-polyposis colorectal cancer. Cancer Detect Prev 25(6):503–510PubMedGoogle Scholar
  27. 27.
    Rossi BM, Lopes A, Oliveira Ferreira F et al (2002) hMLH1 and hMSH2 gene mutation in Brazilian families with suspected hereditary non-polyposis colorectal cancer. Ann Surg Oncol 9(6):555–561PubMedGoogle Scholar
  28. 28.
    Oliveira Ferreira F, Napoli Ferreira CC, Rossi BM et al (2004) Frequency of extracolonic tumors in hereditary non-polyposis colorectal cancer (HNPCC) and familial colorectal cancer (FCC) Brazilian families: An analysis by a Brazilian Hereditary Colorectal Cancer Institutional Registry. Fam Cancer 3(1):41–47CrossRefPubMedGoogle Scholar
  29. 29.
    Henderson TO, Amsterdam A, Bhatia S et al (2010) Systematic review: surveillance for breast cancer in women treated with chest radiation for childhood, adolescent, or young adult cancer. Ann Intern Med 152(7):444–455PubMedGoogle Scholar
  30. 30.
    Vasen HF, Morreau H, Nortier JW (2001) Is breast cancer part of the tumor spectrum of hereditary non-polyposis colorectal cancer? Am J Hum Genet 68(6):1533–1535CrossRefPubMedGoogle Scholar
  31. 31.
    Westenend PJ, Schütte R, Hoogmans MM et al (2005) Breast cancer in an MSH2 gene mutation carrier. Hum Pathol 36(12):1322–1326CrossRefPubMedGoogle Scholar
  32. 32.
    Risinger JI, Barrett JC, Watson P et al (1996) Molecular genetic evidence of the occurrence of breast cancer as an integral tumor in patients with the hereditary non-polyposis colorectal carcinoma syndrome. Cancer 77(9):1836–1843CrossRefPubMedGoogle Scholar
  33. 33.
    Nelson CL, Sellers TA, Rich SS et al (1993) Familial clustering of colon, breast, uterine, and ovarian cancers as assessed by family history. Genet Epidemiol 10(4):235–244CrossRefPubMedGoogle Scholar
  34. 34.
    de Leeuw WJ, van Puijenbroek M, Tollenaar RA et al (2003) Correspondence re: A. Müller et al., Exclusion of breast cancer as an integral tumor of hereditary non-polyposis colorectal cancer. Cancer Res., 62: 1014–1019, 2002. Cancer Res 63(5):1148–1149PubMedGoogle Scholar
  35. 35.
    Boyd J, Rhei E, Federici MG et al (1999) Male breast cancer in the hereditary non-polyposis colorectal cancer syndrome. Breast Cancer Res Treat 53(1):87–91CrossRefPubMedGoogle Scholar
  36. 36.
    Scott RJ, McPhillips M, Meldrum CJ et al (2001) Hereditary non-polyposis colorectal cancer in 95 families: differences and similarities between mutation-positive and mutation-negative kindreds. Am J Hum Genet 68(1):118–127CrossRefPubMedGoogle Scholar
  37. 37.
    Müller A, Edmonston TB, Corao DA et al (2002) Exclusion of breast cancer as an integral tumor of hereditary non-polyposis colorectal cancer. Cancer Res 62(4):1014–1019PubMedGoogle Scholar
  38. 38.
    Itoh H, Houlston RS, Harocopos C, Slack J (1990) Risk of cancer death in first-degree relatives of patients with hereditary non-polyposis cancer syndrome (Lynch type II): a study of 130 kindreds in the United Kingdom. Br J Surg 77(12):1367–1370CrossRefPubMedGoogle Scholar
  39. 39.
    Watson P, Lynch HT (1993) Extracolonic cancer in hereditary nonpolyposis colorectal cancer. Cancer 71(3):677–685CrossRefPubMedGoogle Scholar
  40. 40.
    Aarnio M, Sankila R, Pukkala E et al (1999) Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer 81(2):214–218CrossRefPubMedGoogle Scholar
  41. 41.
    Jass JR (2000) Pathology of hereditary non-polyposis colorectal cancer. Ann NY Acad Sci 910:62–73CrossRefPubMedGoogle Scholar
  42. 42.
    Jensen UB, Sunde L, Timshel S et al (2010) Mismatch repair defective breast cancer in the hereditary non-polyposis colorectal cancer syndrome. Breast Cancer Res Treat 120:777–782CrossRefPubMedGoogle Scholar
  43. 43.
    Meijers-Heijboer H, Wijnen J, Vasen H et al (2003) The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype. Am J Hum Genet 72(5):1308–1314CrossRefPubMedGoogle Scholar
  44. 44.
    Parc Y, Boisson C, Thomas G et al (2003) Cancer risk in 348 French MSH2 or MLH1 gene carriers. J Med Genet 40(3):208–213CrossRefPubMedGoogle Scholar
  45. 45.
    Aarnio M, Mecklin JP, Aaltonen LA et al (1995) Life-time risk of different cancers in hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Int J Cancer 64(6):430–433CrossRefPubMedGoogle Scholar
  46. 46.
    Vasen HF, Stormorken A, Menko FH et al (2001) MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary non-polyposis colorectal cancer families. J Clin Oncol 19(20):4074–4080PubMedGoogle Scholar
  47. 47.
    Watson P, Lynch HT (2001) Cancer risk in mismatch repair gene mutation carriers. Fam Cancer 1(1):57–60CrossRefPubMedGoogle Scholar
  48. 48.
    Goodfellow PJ, Buttin BM, Herzog TJ et al (2003) Prevalence of defective DNA mismatch repair and MSH6 mutation in an unselected series of endometrial cancers. Proc Natl Acad Sci USA 100(10):5908–5913CrossRefPubMedGoogle Scholar
  49. 49.
    Wagner A, Barrows A, Wijnen JT et al (2003) Molecular analysis of hereditary non-polyposis colorectal cancer in the United States: high mutation detection rate among clinically selected families and characterization of an American founder genomic deletion of the MSH2 gene. Am J Hum Genet 72(5):1088–1100CrossRefPubMedGoogle Scholar
  50. 50.
    Franco EL, Villa LL, Ruiz A et al (1995) Transmission of cervical human papillomavirus infection by sexual activity: differences between low and high oncogenic risk types. J Infect Dis 172(3):756–763PubMedGoogle Scholar
  51. 51.
    Kjaer SK, Chackerian B, van den Brule AJ et al (2001) High-risk human papillomavirus is sexually transmitted: evidence from a follow-up study of virgins starting sexual activity (intercourse). Cancer Epidemiol Biomark Prev 10(2):101–106Google Scholar
  52. 52.
    Peyton CL, Gravitt PE, Hunt WC et al (2001) Determinants of genital human papillomavirus detection in a US population. J Infect Dis 183(11):1554–1564CrossRefPubMedGoogle Scholar
  53. 53.
    Burchell AN, Winer RL, de Sanjosé S et al (2006) Chapter 6: epidemiology and transmission dynamics of genital HPV infection. Vaccine 24(Suppl 3):S52–S61CrossRefGoogle Scholar
  54. 54.
    Goecke T, Schulmann K, Engel C et al (2006) Genotype-phenotype comparison of German MLH1 and MSH2 mutation carriers clinically affected with Lynch syndrome: a report by the German HNPCC Consortium. J Clin Oncol 24(26):4285–4292CrossRefPubMedGoogle Scholar
  55. 55.
    Park YJ, Shin KH, Park JG (2000) Risk of gastric cancer in hereditary non-polyposis colorectal cancer in Korea. Clin Cancer Res 6(8):2994–2998PubMedGoogle Scholar
  56. 56.
    Zhang Y, Sheng J, Li S et al (2005) Clinical phenotype and prevalence of hereditary non-polyposis colorectal cancer syndrome in Chinese population. World J Gastroenterol 11(10):1481–1488PubMedGoogle Scholar
  57. 57.
    Lynch HT, Grady W, Suriano G et al (2005) Gastric cancer: new genetic developments. J Surg Oncol 90(3):114–133 (discussion 133)CrossRefPubMedGoogle Scholar
  58. 58.
    Gayther SA, Gorringe KL, Ramus SJ et al (1998) Identification of germ-line E-cadherin mutations in gastric cancer families of European origin. Cancer Res 58(18):4086–4089PubMedGoogle Scholar
  59. 59.
    Guilford P, Hopkins J, Harraway J et al (1998) E-cadherin germline mutations in familial gastric cancer. Nature 392(6674):402–405CrossRefPubMedGoogle Scholar
  60. 60.
    Bevan S, Houlston RS (1999) Genetic predisposition to gastric cancer. QJM 92(1):5–10CrossRefPubMedGoogle Scholar
  61. 61.
    Gylling A, Abdel-Rahman WM, Juhola M et al (2007) Is gastric cancer part of the tumour spectrum of hereditary non-polyposis colorectal cancer? A molecular genetic study. Gut 56(7):926–933CrossRefPubMedGoogle Scholar
  62. 62.
    Mueller-Koch Y, Vogelsang H, Kopp R et al (2005) Hereditary non-polyposis colorectal cancer: clinical and molecular evidence for a new entity of hereditary colorectal cancer. Gut 54(12):1733–1740CrossRefPubMedGoogle Scholar
  63. 63.
    Wijnen J, Khan PM, Vasen H et al (1997) Hereditary nonpolyposis colorectal cancer families not complying with the Amsterdam criteria show extremely low frequency of mismatch-repair-gene mutations. Am J Hum Genet 61(2):329–335CrossRefPubMedGoogle Scholar
  64. 64.
    Nyström-Lahti M, Wu Y, Moisio AL et al (1996) DNA mismatch repair gene mutations in 55 kindreds with verified or putative hereditary non-polyposis colorectal cancer. Hum Mol Genet 5(6):763–769CrossRefPubMedGoogle Scholar
  65. 65.
    Katballe N, Juul S, Christensen M et al (2001) Patient accuracy of reporting on hereditary non-polyposis colorectal cancer-related malignancy in family members. Br J Surg 88(9):1228–1233CrossRefPubMedGoogle Scholar
  66. 66.
    Murff HJ, Spigel DR, Syngal S (2004) Does this patient have a family history of cancer? An evidence-based analysis of the accuracy of family cancer history. JAMA 292(12):1480–1489CrossRefPubMedGoogle Scholar
  67. 67.
    Liu B, Parsons R, Papadopoulos N et al (1996) Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients. Nat Med 2(2):169–174CrossRefPubMedGoogle Scholar
  68. 68.
    Renkonen E, Zhang Y, Lohi H et al (2003) Altered expression of MLH1, MSH2, and MSH6 in predisposition to hereditary nonpolyposis colorectal cancer. J Clin Oncol 21(19):3629–3637CrossRefPubMedGoogle Scholar
  69. 69.
    Lindor NM, Rabe K, Petersen GM et al (2005) Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familial colorectal cancer type X. JAMA 293(16):1979–1985CrossRefPubMedGoogle Scholar
  70. 70.
    Lynch HT, Lynch PM, Lanspa SJ et al (2009) Review of the Lynch syndrome: history, molecular genetics, screening, differential diagnosis, and medicolegal ramifications. Clin Genet 76(1):1–18CrossRefPubMedGoogle Scholar
  71. 71.
    Roy HK, Lynch HT (2003) Diagnosing Lynch syndrome: is the answer in the mouth? Gut 52(12):1665–1667CrossRefPubMedGoogle Scholar
  72. 72.
    de la Chapelle A (2005) The incidence of Lynch syndrome. Fam Cancer 4(3):233–237CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Felipe Carneiro da Silva
    • 1
  • Ligia Petrolini de Oliveira
    • 1
  • Érika Monteiro Santos
    • 2
  • Wilson Toshihiko Nakagawa
    • 2
  • Samuel Aguiar Junior
    • 2
  • Mev Dominguez Valentin
    • 1
  • Benedito Mauro Rossi
    • 2
  • Fábio de Oliveira Ferreira
    • 2
  1. 1.Research Center of the AC Camargo Hospital, Fundação Antônio PrudenteSão PauloBrazil
  2. 2.Hereditary Colorectal Cancer Registry of the A.C. Camargo Hospital, Fundação Antônio PrudenteSão PauloBrazil

Personalised recommendations