Knowledge Translation in Cancer: The Implications of Genetics

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?