1. IX Convegno nazionale ISSE 2010 International Meeting ofSurgicalEndoscopy Familiarity and colorectalcancer Dott. Dario Musto Centro di riferimento regionale per la diagnosi precoce dei tumori eredo-familiari dell’apparato digerente Dir. Prof. G. Riegler U.O. Gastroenterologia ed Endoscopia Digestiva Seconda Università degli Studi di Napoli
2. Familiarity and colorectalcancer Epidemiology 945.000 newdiagnoses/year (WHO) Greenlee RT, Hill-Harmon MB, Murray T, Thun M. Cancer statistics, 2001.CA Cancer J Clin2001 Lineeguidasulcancro del colon retto, ASSR 2002
4. Familiarity and colorectalcancer Classification of colorectal cancer SIDNEY J. WINAWER, et al. Colorectal Cancer Screening: Clinical Guidelines and Rationale GASTROENTEROLOGY 1997;112:594–642
5. Familiarity and colorectalcancer FAMILIARITY INHERITANCE trasmissionoffactorspredisposing the occurrenceofanevent. More easily to find in family members linked to the transmission of genes responsible for the occurrence of "that" particular event FAP HNPCC …Others
8. Familiarity and colorectalcancer RISK EVALUATION AgeFamiliarity Sedentary Dietary factors Personal history of colorectal adenomas or carcinomas Inflammatory bowel disease
26. Familiarity and colorectalcancer Familial Colon Cancer RiskStratification 2–3-fold Increasedrisk Individuals who have a first-degree relative with CRC diagnosed after age 50 years 1 first-degree relative with CRC before age 45 years 3–6-fold increasedrisk 2 first-degree relatives affected with CRC Johns LE, Houlston RS. A systematic review and meta-analysis of familial colorectal cancer risk. Am J Gastroenterol2001
27. Familiarity and colorectalcancer Common Familial Risk Colon Cancer Individuals who have a first-degree relative with CRC diagnosed after age 50 years 1 or more second-degree or third-degreerelativeswith CRC High-RiskFamilial Non-syndromic Colon Cancer Individuals who have a first-degree relative with CRC diagnosed before age 50 years 2 first-degreerelatives affected with CRC Jasperson KW, Burt RW – Hereditary and Familial Colon CancerGastroenterology 2010
28. Familiarity and colorectalcancer High-RiskFamilial, Nonsyndromic Colon Cancer Amsterdam II Criteria 0.8% to 2.3% ofall CRC No mutations in MMR System Familialcolorectalcancertype X Lindor NM, Rabe K, Petersen GM, et al. Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familialcolorectalcancertype X. JAMA 2005.
29. Familiarity and colorectalcancer Familialcolorectalcancertype X CRC risk is lower than in Lynch syndrome CRC diagnosis averages 10 years later tumors do not exhibit MSI No increased incidence of extracolonic malignancies Genes and their mechanism involved unknown but sufficiently penetrant to express their pathogeneticity Lindor NM, Rabe K, Petersen GM, et al. Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency: familialcolorectalcancertype X. JAMA 2005.
30. Familiarity and colorectalcancer Common Familial Risk Colon Cancer Common familial CRCs arise from a number of different, lower-penetrance susceptibility genes than those associated with the well-defined but rare inherited syndromes. APC-I1307K The variantsidentified at susceptibility loci are not “mutations” They might affect gene expression through noncoding changes or lead to linkage disequilibrium with other genes that affect CRC risk. HRAS1-VNTR MTHFR TCF7L2 TGFBR1*6A SMAD7 Jasperson KW, Burt RW – Hereditary and Familial Colon CancerGastroenterology 2010
31. Familiarity and colorectalcancer Genetics Environment Multiple polymorphisms or variantsinfluencecolon cancer susceptibility, but may differ in their affect depending on the genetic, environmental, or clinical context. Jasperson KW, Burt RW – Hereditary and Familial Colon CancerGastroenterology 2010
35. Familiarity and colorectalcancer Surveillance Patientswith a single first-degree relative older than age 60 years with colon cancer should receive standard, average-risk colon cancer screening, but starting at age 40 years Patientswhohave 1 relative with CRC before 60 years or 2 first-degree relatives with CRC should be screened every 5 years by colonoscopy, starting at age 40 years, or at an age 10 years younger than the earliest case in the family Patients with only second- or third-degree relatives with CRC should receive average-risk screening Jasperson KW, Burt RW – Hereditary and Familial Colon CancerGastroenterology 2010
36. Familiarity and colorectalcancer Conclusions A detailed analysis of family history is a fundamental component for the evaluation of CRC risk Itisnot only important for identifying patients that are at high risk for CRC and should receive genetic counseling, but also essential for identifying individuals with moderate risk that should receive more aggressive screening.
37. Familiarity and colorectalcancer Thankyoufor the attention The family historyisoneof the mostpowerfulmethodsforidentificationofcancerrisk and providesusefulguidelinesforsurveillance and management. Henry T. Lynch
