knowledge translation in cancer: the implications of genetics
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Knowledge Translation in Cancer:
The Implications of Genetics for Cross-cultural Cancer
CareWilliam H. McKellin, PhDDepartment of Anthropology and Sociology
Doctor, Patient and Society Courses
Faculty of Medicine
Hereditary Cancer Program, BCCA
Cultural Communities
Knowledge Translation: Cancer Genetics and Cancer Care
• Cross-cultural Knowledge Translation in Medicine
• Creating Meanings by Analogy
• Culture Change- Genetics and Cross-cultural Cancer Care
Genetic Promises
• The Human Genome Project is catalyzing discovery of cancer genes and development of:– predictive tests to identify genetic
predisposition– diagnostic tests to detect cancer in its
earliest stages– therapies that target gene abnormalities in
cancer cells- Am Soc Clinical Oncology 1998
The Human Genome and Cancer
• All cancers arise from genetic alterations
• Tumorigenesis is a multi-step process
• About 5% to 10% of cancer is hereditary
Cancer Arises From Gene Mutations
Germline mutations Somatic mutations
Somatic Somatic mutation (eg, mutation (eg,
breast)breast)
Mutation Mutation in egg or in egg or
spermsperm
All cells All cells affected in affected in offspringoffspring
ParentParent ChildChild
Present in egg or spermPresent in egg or sperm Are heritable Are heritable Cause cancer family Cause cancer family
syndromessyndromes
Occur in nongermline Occur in nongermline tissues tissues
Are nonheritableAre nonheritable
Oncologists and Geneticists
• Common Training
• Same institution
• Same first language
• Different second languages
• Different cultures
Medical Model
Disease State
Causative Agent
Locus
Diagnosis
Intervention
Family
Medical Oncology Perspective
Disease State Symptomatic cancer patient
Causative agent Somatic mutation
Locus Organ tumor
Diagnosis Tissue pathology
Intervention Chemotherapy
Family Patient support
Predictive Genetic Testing
• Gene based predictive testing for hereditary risk
• What do oncologists and Family Practitioners need to know?
BRCA1
• Tumor suppressor gene on chromosome 17 • Autosomal dominant transmission • Protein has role in genomic stability• ~500 different mutations reported
Breast Cancer Information CoreBreast Cancer Information Core
Nonsense Nonsense MissenseMissense Splice-siteSplice-site
BRCA1-Associated Cancers:Lifetime Risk
Possible increased risk of other Possible increased risk of other cancers (eg, prostate, colon)cancers (eg, prostate, colon)
Breast cancerBreast cancer 50% 50%85% (often early age at onset)85% (often early age at onset)
Second primarySecond primary breast cancerbreast cancer 40% 40%60%60%
Ovarian cancerOvarian cancer 15% 15%45%45%
BRCA2
• Tumor suppressor gene on chromosome 13
• Autosomal dominant transmission
• Protein has role in genomic stability
• ~300 different mutations reported
Breast Cancer Information CoreBreast Cancer Information Core
Nonsense Nonsense MissenseMissense Splice-siteSplice-site
BRCA2-Associated Cancers: Lifetime Risk
Increased risk of prostate, Increased risk of prostate, laryngeal, and pancreatic cancers laryngeal, and pancreatic cancers
(magnitude unknown)(magnitude unknown)
breast cancerbreast cancer (50%(50%85%)85%)
ovarian cancerovarian cancer (10%(10%20%)20%)
male breast cancermale breast cancer (6%)(6%)
Genetic Heterogeneity in HNPCC
HNPCCHNPCC is associated with germline is associated with germline mutations in any one of at least five mutations in any one of at least five
genesgenes
ChrChr 22ChrChr 33
Chr 7Chr 7
MSH2MSH2
PMS1PMS1
MLH1MLH1PMS2PMS2
MSH6MSH6
Cancer Risks in HNPCC
AarnioAarnio M et al. M et al. Int JInt J CancerCancer 64:430, 199564:430, 1995
% with % with cancercancer
100100
8080
6060
4040
2020
002020 4040 6060 808000
Age (years)Age (years)
Colorectal Colorectal 78%78%
EndometrialEndometrial 43% 43%
Stomach Stomach 19%19%Biliary tractBiliary tract 18%18%Urinary tractUrinary tract 10%10%OvarianOvarian 9%9%
ASCO
Medical Genetics Perspective
Disease State At-risk for mutation
Causative Agent Germline mutation
Locus Pleotropic
Diagnosis DNA test
Intervention Predictive risk counselling
Family Shared risk status
Oncology Genetics
Disease State Symptomatic cancer patient
At-risk for mutation
Causative agent Somatic mutation Germline mutation
Locus Organ tumor Pleotropic
Diagnosis Tissue pathology DNA test
Intervention Chemotherapy Predictive risk counselling
Family Patient support Shared risk status
Knowledge Translation:Transmission models
• Science Push
• Clinical/Policy Pull
• Assumptions: – Information is an object – Information is passed though a conduit – Translation is passive acceptance by the
audience
Knowledge Translation: Interaction models
• Information is only a raw material• Interaction is a process that creates meaning
– Cultural Creolization (Hannerz 1992)
– Conceptual Integration and Blending (Faucconier and Turner 1998, 2002)
• Interaction makes participants to create new analogies and concepts
Conceptual Integration and Blending
• Decompose established knowledge– Restricted codes– Elaborating codes
• Identify shared elements of knowledge• Identify incompatible elements• Negotiate mutual relevances• Synthesize new meanings
– Meanings are networks of perspectives
Cancer Genetics and Emerging Psychosocial Issues
• Role of Families • Predictive and diagnostic testing • Ethnicity
Cancer as a Familial Disease
• Oncology– Disclosing cancer diagnosis
to family
– Family as patient support
– Responsibility for patient care
• Genetics– Disclosing risk status to
other family members at risk
– Shared inherited risk and vulnerability
– Mutual responsibility for disease
• Heredity
• Environmental exposure
– Patient expertise in genetics
The Cancer Family
• What are the key issues that patients and family members attempt to “map onto” clinicians’ expectations of their roles?
• What language do they use?
• What expertise do patients and their families develop?
Predictive and Diagnostic TestingWhat is a genetic test?
• Predictive genetic tests– Risk status of
individual tested• BRCA1 /2, HNPCC
– Implications for other family members’ risk
– Founder mutations
– Familial mutations
Predictive and Diagnostic TestingWhat is a genetic test?
• Predictive genetic tests– Risk status of
individual tested• BRCA1 /2, HNPCC
– Implications for other family member’s risk
– Founder mutations
– Familial mutations
• Diagnostic genetic tests– Detect disease
• MSI - colon cancer
– Ambiguous relevance to family members
– May lead to mutation testing
– Familial mutations
Predictive and Diagnostic Genetic Tests
• What is the relationship between a mutation and a form of the disease?
• Are predictive tests used as a form of diagnosis?• Why should a patient have a genetic test if
reproduction is not a concern?• Are genetic tests just like other types of medical
tests?• Do genetic diagnostic tests provide too much
information about the individual and family?
Ethno-cultural groups and Founder populations
• Genetic (essentialist) definitions of ethnocultural groups– Defining genotypes– Genetic heterogeneity
• Genetic stereotyping of communities– Associated conditions
• Kinship and marriage in contrast to patterns of heredity
• Targeted testing and therapies• Community control of genetic and population
health information
EthnicityRelation Ethno-cultural Founder Population
Group definition Language, health beliefs, etc.
Genome, characteristic mutations
Group membership
Self-identify Identified though testing
Structure Kinship Heredity
Cancer Care Cultural competence
Targeted testing and intervention
Individual to group
Situational variable
Community genome ownership?
Ethnicity
• How will ethnocultural groups change with-– Genetic testing for founder mutations?– Diagnostic genetic testing that reveals family
information?– Control of community genetic information?– Development of population-specific therapies?
Cancer Genetics and Cross-cultural Cancer Care
• Genetics is producing a culture change in medicine– Patients without disease– The family (and even extended family) as patient– Follows patients developmentally over time– Disease and community involvement– Linkage of counselling to advanced medical science– Environmental exposure and genetics– Targeted therapies
• How will genetics change the way that care-givers and patients share knowledge?