1 / 24

Hereditary Colorectal Cancer: From Genetic Testing to Prevention

Hereditary Colorectal Cancer: From Genetic Testing to Prevention. Robert E. Schoen, MD MPH Associate Professor of Medicine and Epidemiology Division of Gastroenterology University of Pittsburgh. Colorectal Cancer - Epidemiology. 2nd leading cause of CA mortality in U.S.

gloriai
Télécharger la présentation

Hereditary Colorectal Cancer: From Genetic Testing to Prevention

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Hereditary Colorectal Cancer: From Genetic Testing to Prevention Robert E. Schoen, MD MPH Associate Professor of Medicine and Epidemiology Division of Gastroenterology University of Pittsburgh

  2. Colorectal Cancer - Epidemiology • 2nd leading cause of CA mortality in U.S. • > 130,000 new cases/yr • > 48,000 deaths/yr

  3. Estimated Cancer Deaths in U.S. - 1999 Men Women Lung - 31% Lung - 25% Prostate - 13% Breast - 16% Colorectal - 10% Colorectal - 11%

  4. Lifetime Risk of CRC (%) Male + Female LR Dx LR Death All Races 5.88 2.57 Whites 5.99 2.63 Blacks 4.42 2.14 SEER, 1992 - 4

  5. Etiologic Concepts in CRC

  6. Colorectal Cancer 1%

  7. Click for larger picture

  8. Intermediate Endpoint Environment Alteration in Large Bowel Epithelium Cancer Host

  9. Polymorphisms and CRC Risk Low penetrance susceptibility alleles- Meta Analysis OR APC I1307K 1.6 (1.2 - 2.1) HRAS1-VNTR 2.5 (1.5 - 4.1) MTHFR (val/val) 0.8 (0.6 - 0.9) P53, NAT1, NAT2, GSTM1, GSTT1, GSTP1 exclude >1.7 fold increase Houlston, Gastro 2001;121:282

  10. Consensus Guidelines > = 50  Options:  Annual FOBT  FS q 5 yrs  FOBT + FS  DCBE q 5-10 yr  Colon q 10 yr  + TCE: Colonoscopy or DCBE + FS Gastro. 1997:112;594

  11. Familial CRC

  12. Family Hx - Prospective StudyNHS & HPFS (1) 87,000 women; 32,000 men 315 and 148 cases CRC RR = Incidence CRC with fm hx* CRC Incidence CRC with NO fm hx CRC 1o relative = mother, father, sibs Fuchs et al; NEJM 1994;331:1669-74

  13. Family Hx - Prospective StudyNHS & HPFS (2) Family Hx CRC reported by 10% of sample RR CRC with Fm Hx = 1.7* * adjusted for diet, ASA, physical activity, cigs, screening endoscopy Fuchs et al; NEJM 1994;331:1669-74

  14. Family Hx - Prospective StudyNHS & HPFS (3) Conclusions: • Risk with 2 or more 1o relatives •  Risk with family member  55

  15. AHCPR Guidelines Family Hx • CRC in 1 or 2 (?) FDR • Adenomas in FD relative  60 Same Options as Avg Risk, but Start at age 40 Gastro 1997:112;594

  16. Germline Mutations

  17. Gastro 2001;121:195

  18. HNPCC - Clinical Characteristics • Autosomal dominant, highly penetrant • CRC <age 45,  synchro/proximal • Polyps - larger, more aggressive; cancers better prognosis • Endometrial, ovarian, other CA’s

  19. HNPCC Recognition • Early onset cancers • Multiple cancers in successive generations • Association with other cancers - endometrial

  20. HNPCC - “Amsterdam Criteria” • Three or more relatives with CRC, one of whom is 1o relative of other two • CRC in at lest 2 generations • One or more cases before age 50

  21. Amsterdam Criteria II 3 Relatives with HNPCC associated CA: CRC, Endometrial, Small Bowel Ureter, Renal Pelvis • 1 should be 1o Relative of other 2 • 2 successive generations (at least) • 1 diagnosed before age 50 FAP excluded Verify Tumors

  22. CRC@40 CRC@56 Endomet @48 CRC@45 CRC@68 CRC@48

More Related