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

Genes in the News

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

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

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

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

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

Different Genes – Different Functions Pancreas CellBone CellBrain Cell

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

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

Disease-Linked Genes Cancer gene markersCancer gene

DNA DNA molecule (chromosome) Cell Nucleus Gene Chromosomes

DNA Molecules CellChromosomesNucleus

How many genes are we talkin’? Chromosome X

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

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

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

Gene Mutations Mismatch DuplicationDeletion Frameshift Deletion

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

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

Technical Concerns

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

Genetic Tests Find Mutations, NOT Disease Chances of Developing Breast Cancer by Age 65 Normal BRCA1 Altered BRCA

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, ??

What’s my risk for cancer?

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

Importance of Family History

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

Benefits of Gene Testing Relief Fewer Checkups Informed Decisions Intervention

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

Major Limitations of Gene Testing

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

Psychological Consequences

Who Should Know?

Confidentiality Concerns

Personal Decision

Difficult Decision Want To Know Don’t Want To Know Percent of Population

Importance of Genetic Counselors

Thank you for listening! If you would like more information about cancer genetics for yourself, a friend or family member, Call (925) 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