Understanding Hereditary Cancers

Brittany Burnett, MS, CGCCertified Genetic CounselorJohn Muir/Mt. Diablo Health SystemCancer Centers

Genes in the News

Factors Affecting Whether Factors Affecting Whether AnyAny Person Gets CancerPerson Gets Cancer

Hormonal/ Hormonal/ reproductive reproductive

factorsfactors

Modifier genesModifier genesCarcinogensCarcinogens

Response to DNA Response to DNA damagedamage

Many Mutations Lead to Cancer

Malignant Cells

NormalCell

FirstMutation

SecondMutation

ThirdMutation

Fourth orLater

Mutation

Acquired Mutations

Altered Bone Cells

Normal Bone Cell

Normal Bone Cells

Mutation Occurs

Altered Gene

Hereditary Mutations

Fertilized Egg

Mutation Occurs

BrainPancreasBoneReproductive

Body Cells of Offspring

Mutation

SpermEgg

Many Mutations Lead to Cancer

Malignant Cells

NormalCell

FirstMutation

SecondMutation

ThirdMutation

Fourth orLater

Mutation

Different Genes – Different Functions

Pancreas CellBone Cell Brain Cell

Most Cancer Is NOT Inherited

Known Inherited Factor

All Breast Cancer Patients

Unknown Factor(s)

Searching Disease Families

Cancergene

Disease Present

Disease Absent

Cancer genemarkers

Disease-Linked Genes

Cancer gene markers Cancer gene

DNA

DNA molecule (chromosome)

Cell

Nucleus

Gene

Chromosomes

DNA Molecules

Cell ChromosomesNucleus

How many genes are we talkin’?

Chromosome X

Chemical Bases in DNA

DNA molecule (chromosome)

Chemical bases

Gene

AT

CG

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

Duplication Deletion

Frameshift Deletion

Gene Tests – Three Common Methods

Chromosome

Mutation Absent Mutation Present

Protein

DNA

Microarray Analysis

RNA prep

1.5 x 103 cellscDNA microarrays

High-throughput gene expression analysis

cDNA libraries

TotalRNA cDNA

(10–50 ng) oligo(dT)

EST sequencing

Technical Concerns

Searching Disease Families

Cancergene

Disease Present

Disease Absent

Cancer genemarkers

Genetic Tests Find Mutations, NOT DiseaseChances of Developing Breast Cancer by Age 65

Normal BRCA1Altered BRCA1

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What are some of the cancer What are some of the cancer syndromes?syndromes?

Breast cancer genes: BRCA1, BRCA2, Breast cancer genes: BRCA1, BRCA2, p53, PTENp53, PTEN

Colon cancer genes: MLH1, MSH2, Colon cancer genes: MLH1, MSH2, MSH6, PMS2, APCMSH6, PMS2, APC

Melanoma genes: p16, othersMelanoma genes: p16, others

Renal/kidney cancer genes: pVHL, othersRenal/kidney cancer genes: pVHL, others

Prostate cancer genes: MSR1, ??Prostate cancer genes: MSR1, ??

What’s my risk for cancer?

The Genetic Counseling ProcessThe Genetic Counseling Process

Need to determine if testing is Need to determine if testing is reasonablereasonable

Evaluate for all cancer syndromesEvaluate for all cancer syndromes

Keep up with changing information on Keep up with changing information on diagnosis and testing methodsdiagnosis and testing methods

Psychological and social impact on Psychological and social impact on the patient and his/her familythe patient and his/her family

Long-term follow-upLong-term follow-up

Importance of Family HistoryImportance of Family History

The Questions We Ask…The Questions We Ask…Age and cause of deathPhysical findingsEnvironmental exposuresAnyone with previous Anyone with previous testing?testing?Origin of cancer(s)Origin of cancer(s)Age of onsetAge of onsetUnilateral/bilateralUnilateral/bilateral2nd Primaries2nd PrimariesCurrent cancer Current cancer surveillancesurveillanceEthnic backgroundEthnic background

Dominant Pedigree

= Affected

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 What Happens If We Find a Mutation?Mutation?

PositivePositive genetic test result genetic test result

Possible testing for Possible testing for other adult relativesother adult relatives

IncreasedIncreasedsurveillancesurveillance

ProphylacticProphylacticsurgerysurgery

Lifestyle Lifestyle changeschanges

Chemo-Chemo-preventionprevention

Psychological Consequences

Who Should Know?

Confidentiality Concerns

Personal Decision

Difficult Decision

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Importance of Genetic Counselors

Thank you for listening!Thank you for listening!

If you would like more information about cancer geneticsfor 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