Understanding Hereditary Cancers

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

2. Genes in the News

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

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

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

7. Hereditary Mutations Egg Sperm Mutation Occurs Fertilized Egg Mutation Reproductive Bone Pancreas Brain Body Cells of Offspring

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

9. Different Genes – Different Functions Bone Cell Pancreas Cell Brain Cell

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

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

12. Disease-Linked Genes Cancer gene markers Cancer gene

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

14. DNA Molecules Cell Nucleus Chromosomes

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

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

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

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

19. Gene Mutations Frameshift Deletion Mismatch Duplication Deletion

20. Gene Tests – Three Common Methods Mutation Absent Mutation Present Chromosome DNA Protein

21. Microarray Analysis 1.5 x 103 cells TotalRNA cDNA cDNA microarrays RNA prep (10–50 ng) oligo(dT) cDNA libraries EST sequencing High-throughput gene expression analysis

22. Technical Concerns

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

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

25. 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, ??

26. What’s my risk for cancer?

27. 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 The Genetic Counseling Process

28. Importance of Family History

29. 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 The Questions We Ask…

30. Benefits of Gene Testing • Relief • Fewer Checkups • Informed Decisions • Intervention

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

32. Major Limitations of Gene Testing

33. What Happens If We Find a Mutation? Positive genetic test result Possible testing for other adult relatives Increased surveillance Lifestyle changes Chemo- prevention Prophylactic surgery

34. Psychological Consequences

35. Who Should Know?

36. Confidentiality Concerns

37. Personal Decision

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

39. Importance of Genetic Counselors

40. 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