genetic risk assessment and genetic counseling research

30 January 200630 January 2006

Genetic Risk Genetic Risk Assessment and Assessment and Genetic Counseling Genetic Counseling ResearchResearchJohn QuillinJohn QuillinHuman GeneticsHuman GeneticsVirginia Commonwealth UniversityVirginia Commonwealth University

Outline for todayOutline for today Of Risk and PopcornOf Risk and Popcorn Cancer Risk FactorsCancer Risk Factors Genetic Risk AssessmentGenetic Risk Assessment Implications for Cancer ControlImplications for Cancer Control Genetic Counseling ResearchGenetic Counseling Research

Of Risk and PopcornOf Risk and Popcorn

Of Risk and PopcornOf Risk and Popcorn

0

50

100

150

200

250

0 to 0.5 0.5 to 1 1 to 1.5 1.5 to 2 2 to 2.5 2.5 to 3 3 to 3.5 3.5 to 4 4 to 4.5

Minutes

# of

Pop

s

Of Risk and PopcornOf Risk and Popcorn

0

50

100

150

200

250

0 to 0.5 0.5 to 1 1 to 1.5 1.5 to 2 2 to 2.5 2.5 to 3 3 to 3.5 3.5 to 4 4 to 4.5

Minutes

# of

Pop

s N = 250 (per bag)

Of Risk and PopcornOf Risk and Popcorn

0

50

100

150

200

250

0 to 0.5 0.5 to 1 1 to 1.5 1.5 to 2 2 to 2.5 2.5 to 3 3 to 3.5 3.5 to 4 4 to 4.5

Minutes

# of

Pop

s N = 250 (per bag)

Cumulative Risk

What determines if a What determines if a kernal pops?kernal pops?

External factorsExternal factors How long it’s in the microwaveHow long it’s in the microwave The type of microwaveThe type of microwave Oil/seasoningsOil/seasonings

Internal factorsInternal factors Genes (genetically-modified corn??)Genes (genetically-modified corn??) Soil/nutrientsSoil/nutrients

Breast Cancer RiskBreast Cancer Risk

0

50

100

150

200

250

0 to 20 20 to 40 40 to 60 60 to 80 80 to 95+

Years

# pe

r 25

0 w

ith

Bre

ast

Can

cer

What affects cancer risk?What affects cancer risk?

DietTobaccoHereditaryOccupationRadiationVirusesOther

Sporadic Familial Mendelian

Family History and Chance of Breast Cancer

0

10

20

30

40

50

60

70

80

90

100

Mother Two Paternal Aunts Mother and MaternalAunt

Mother and Sister

Family History

Num

ber w

ith B

reas

t Can

cer o

ut o

f 10

0 W

omen

Claus, 1990

Twin StudiesTwin StudiesBreast Cancer in Twins

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Identical Twins Fraternal Twins

Perc

ent W

ithin

Eac

h G

roup

One Has CancerBoth Have Cancer

N Engl J Med 2000;343:78-85

Causes of Breast Cancer

27%

6%

67%

Genetics Shared Environment Unique Environment

BRCA1 and BRCA2BRCA1 and BRCA2

Science 2003;302(5645):643-6

More likely to be More likely to be hereditary if…hereditary if…

Earlier-than-expected age of onsetEarlier-than-expected age of onset Multiple primary cancersMultiple primary cancers Rare cancersRare cancers Inheritance patternInheritance pattern Syndrome (malignant and non-malignant Syndrome (malignant and non-malignant

characteristics)characteristics) No clear environmental associationNo clear environmental association

Peutz-Jeghers SyndromePeutz-Jeghers Syndrome

Cancer Control Cancer Control ImplicationsImplications

Primary preventionPrimary prevention Medication (e.g., tamoxifen, sulindac)Medication (e.g., tamoxifen, sulindac) Risk-reducing surgeryRisk-reducing surgery Lifestyle (e.g., exercise)Lifestyle (e.g., exercise) Diet (coffee??)Diet (coffee??)

Secondary preventionSecondary prevention Timing (age of initiation, interval)Timing (age of initiation, interval) Method (MRI)Method (MRI) Whether or not to screen at allWhether or not to screen at all

Cancer Control Cancer Control ImplicationsImplications

Tertiary preventionTertiary prevention ChemotherapyChemotherapy Extent of surgeryExtent of surgery RadiationRadiation

Why genetic counseling?Why genetic counseling? Risk communication is complicatedRisk communication is complicated Diagnosis/risk assessment often precedes Diagnosis/risk assessment often precedes

effective interventioneffective intervention Right not to knowRight not to know Psychosocial cost/benefitPsychosocial cost/benefit

Limitations of testing (VUS, false negative)Limitations of testing (VUS, false negative) ExpensiveExpensive DiscriminationDiscrimination

Tailored Treatment and Prevention

Improved Public Health

Cancer Diagnosis

Genetic Counseling

Discussion with Family Members

High Riskfor Cancer

A lot of focus here

GENETIC COUNSELING RESEARCH

Maternal/Paternal HistoryMaternal/Paternal History

SummarySummary About 5-10% cancers hereditaryAbout 5-10% cancers hereditary Prevention/management implicationsPrevention/management implications DNA testing available butDNA testing available but

Imperfect, expensive, complicatedImperfect, expensive, complicated Identification and access are important Identification and access are important

challengeschallenges