2. Understanding Hereditary Cancers Brittany Burnett, MS, CGC Certified Genetic Counselor John Muir/Mt. Diablo Health System Cancer Centers

3. Genes in the News

5. Factors Affecting Whether Any Person Gets Cancer Hormonal/ reproductive factors Modifier genes Carcinogens Response to DNA damage

6. Many Mutations Lead to Cancer Malignant Cells Normal Cell First Mutation Second Mutation Third Mutation Fourth or Later Mutation

7. Acquired Mutations Altered Bone Cells Normal Bone Cell Normal Bone Cells Mutation Occurs Altered Gene

8. Hereditary Mutations Fertilized Egg Mutation Occurs BrainPancreas Bone Reproductive Body Cells of Offspring Mutation SpermEgg

9. Many Mutations Lead to Cancer Malignant Cells Normal Cell First Mutation Second Mutation Third Mutation Fourth or Later Mutation

10. Different Genes – Different Functions Pancreas CellBone CellBrain Cell

11. Most Cancer Is NOT Inherited Known Inherited Factor All Breast Cancer Patients Unknown Factor(s)

12. Searching Disease Families Cancer gene Disease Present Disease Absent Cancer gene markers

13. Disease-Linked Genes Cancer gene markersCancer gene

14. DNA DNA molecule (chromosome) Cell Nucleus Gene Chromosomes

15. DNA Molecules CellChromosomesNucleus

16. How many genes are we talkin’? Chromosome X

17. Chemical Bases in DNA DNA molecule (chromosome) Chemical bases Gene A T C G

18. DNA->RNA->Protein Nucleus DNA bases mRNA DNA Protein Ribosome Cell membrane Gene Chain of amino acids

19. Altered DNA->Altered Protein NucleusDNA Protein Chain of amino acids Ribosome Gene DNA bases mRNA Cell membrane

20. Gene Mutations Mismatch DuplicationDeletion Frameshift Deletion

21. Gene Tests – Three Common Methods Chromosome Mutation AbsentMutation Present Protein DNA

22. Microarray Analysis RNA prep 1.5 x 10 3 cells cDNA microarrays High-throughput gene expression analysis cDNA libraries Total RNA cDNA (10–50 ng)oligo(dT) EST sequencing

23. Technical Concerns

24. Searching Disease Families Cancer gene Disease Present Disease Absent Cancer gene markers

25. Genetic Tests Find Mutations, NOT Disease Chances of Developing Breast Cancer by Age 65 Normal BRCA1 Altered BRCA1 0 10 20 30 40 50 60 70 80 90 100 0 10 20 30 40 50 60 70 80 90 100

26. What are some of the cancer syndromes? Breast cancer genes: BRCA1, BRCA2, p53, PTEN Colon cancer genes: MLH1, MSH2, MSH6, PMS2, APC Melanoma genes: p16, others Renal/kidney cancer genes: pVHL, others Prostate cancer genes: MSR1, ??

27. What’s my risk for cancer?

28. The Genetic Counseling Process Need to determine if testing is reasonable Evaluate for all cancer syndromes Keep up with changing information on diagnosis and testing methods Psychological and social impact on the patient and his/her family Long-term follow-up

29. Importance of Family History

30. The Questions We Ask… Age and cause of death Physical findings Environmental exposures Anyone with previous testing? Origin of cancer(s) Age of onset Unilateral/bilateral 2nd Primaries Current cancer surveillance Ethnic background

31. Benefits of Gene Testing Relief Fewer Checkups Informed Decisions Intervention

32. Limitations of Gene Testing Mutation Present But: May Never Lead to Disease May Go Undetected

33. Major Limitations of Gene Testing

34. What Happens If We Find a Mutation? Positive genetic test result Possible testing for other adult relatives IncreasedsurveillanceProphylacticsurgery Lifestyle changes Chemo-prevention

35. Psychological Consequences

36. Who Should Know?

37. Confidentiality Concerns

38. Personal Decision

39. Difficult Decision 100 50 40 30 20 10 0 Want To Know Don’t Want To Know Percent of Population

40. Importance of Genetic Counselors

41. Thank you for listening! If you would like more information about cancer genetics for yourself, a friend or family member, Call (925) 674-2581 and we’ll be happy to speak with you. Or just ask your doctor if it’s right for you. Thanks again, Brittany Burnett, MS, CGC