community participation in cancer discovery research ... · community participation • community...
Post on 04-Aug-2020
0 Views
Preview:
TRANSCRIPT
Community Participation in Cancer Discovery Research: Linking Biology,
Cancer Disparities, and Dissemination
Robert A. Hiatt
UCSF Helen Diller FamilyComprehensive Cancer Center
July 13, 2011Bethesda, MD
Question?
• How can basic research on the origins of cancer disparities be 1) better understood by the public and 2) better disseminated to the people who are intended to benefit from the results?
Community Participation
• Community Based Participatory Research (CBPR) is not new, but its application to discovery research is unusual.
• For cancer disparities research that takes a transdisciplinary approach and seeks to integrate basic biologic understanding into a fuller picture of its origins, dissemination can be a challenge.
Community Participation
• How can community participation be integrated into cancer disparities research for the benefit of science and the public health?
• An example from the Breast Cancer and the Environment Research Centers, an NCI/NIEHS sponsored national network.
The Breast Cancer and the Environment Research Centers
Research Question
Do environmental factors contribute to the etiology of breast cancer in humans?
What evidence motivates this question?
Female Breast Cancer Incidence Ratesage-standardized rates, 1988-1992
From Parkin, et al., IARC, 1997
Cases/100,000 p-yrs
Variation in Breast Cancer Rates, Japaneseage-standardized incidence rates, 1988-1992
From Parkin, et al., IARC, 1997
Cases/100,000 p-yrs
Research Approaches
• Mechanistic
• Animal studies
• Epidemiology
.
Epidemiologic Studies
• Most have been performed in adults
• Study designs have followed case-control or cohort approaches.
• Some natural experiments
Selected Factors Known to Influence Breast Cancer
Risk Factor Comparison RR 95% CIAge at menarche ≥15 vs. <12 y 0.72 (0.62-0.82)Parity ≥3 vs. none 0.72 (0.61-0.86)Age at First Birth >30 vs. ≤20 y 1.46 (1.22-1.75)Education >HS vs. <HS 1.08 (0.90-1.29)BBD Yes vs. No 1.53 (1.41-1.65)Maternal History Yes vs. No 1.38 (1.14-1.67)Sister History Yes vs. No 1.47 (1.27-1.70)From Hunter DJ, et al. Cancer Causes Control 1997;8:49-56. Analysis includes 322,647 women followed for 5-7 years, with 4,827 incident cases of breast cancer.
Seasons of Life & Breast Cancer Risk
• In utero: birthweight; in utero exposures?
• Infancy: infant feeding practices?
• Early childhood: growth patterns?
• Adolescence: earlier age at menarche increases risk
• Young adulthood: late age at first birth increases risk
• Childbearing years: greater parity decreases risk; breastfeeding decreases risk
• Menopausal transition: late menopause increases risk; use of HRT increases risk
• Postmenopausal years: lifetime body weight patterns influence risk
Has led to more interest in “windows of susceptibility”
Puberty
Reasons for interest as a window of susceptibility:
• Time of rapid development of both epithelial cells and stroma.
• Period of rapid growth in height.
• Age of menarche highly variable internationally
• Age of menarche dropping over last century with industrialization
The Changing Age of Puberty Over Time
International Trends in Age at Menarche
Korean example
Cho GJ et al. Eur J Pediatrics 2010
Prevalence of Breast Developmentat Tanner Stage 2 or Greater by Age and Race
Herman-Giddens et al., Pediatrics, 1997
Height & Breast CancerPooled Analysis, Cohort Studies of Diet & Breast Cancer
Cohort
Rela
tive
Ris
k,H
eigh
t (m
) ≥1
.68
vs <
1.6
Pooled RR = 1.25 (1.14-1.37)
from van den Brandt, et al., Am J Epidemiol, 2000
Median Age at Maturation MilestonesNHLBI Growth and Health Study, Biro et al., Pediatrics, 2006
New Approach
• Age at menarche an established risk factor
• Puberty a time of rapid breast development
• Changing age for initiation of puberty -likely due to environmental factors
• So…
• Take a life-course approach
• Focus on early development
Bay Area Breast Cancer & Environment Research Center
Project 1: Environmental Effects on the Molecular Architecture and Function of the Mammary Gland across the Lifespan.PI: Zena Werb, PhD, UCSF
Project 2:
COTC:
Environmental and Genetic Determinants of PubertyPI: Lawrence Kushi, ScD, KP/DOR
PI: Robert A. Hiatt, MD, PhD, UCSF CCC
Community Outreach and Translation CorePI: Janice Barlow, RN, Zero Breast Cancer
Breast Cancer and the Environment Research Centers (BCERCs)
Cincinnati Children’s HospitalUCSFLBNL
Michigan State University
University of Cincinnati
Mount SinaiSchool of Medicine
Fox Chase Cancer Center
Kaiser Permanente
University of Alabama
NIEHS
NCI
Zero BreastCancer
Funding Agencies
BCERC Prime Institutions
Collaborating Institutions
Roswell ParkCancer Institute
University of MichiganCalifornia Departmentof Health Services
Marin County DHHS
Project 1 - Specific Aims
Specific Aim 1: Determine the alterations in the mammary microenvironment andthe mammary cells in normal and cancer prone mice in vivo during prenataldevelopment, pubertal branching morphogenesis, pregnancy and aging.
Specific Aim 2: Determine the effects of exposure to prototypical environmentalstressors during prenatal development, pubertal branching morphogenesis,pregnancy and aging on the mammary gland in normal and cancer prone mice invivo
Specific Aim 3: Determine the effects of environmental agents implicated fromstudies in Project 2 on regulating the mammary microenvironment of mammarycells during branching morphogenesis
Specific Aim 4: Validate the animal experiments by determining how these environmental stressors affect human mammary epithelial cells in culture through the telomere crisis, comparing the critical endpoints derived from the animal.
Distinct mechanisms pattern the mammary gland
Adapted from Wiseman & Werb (2002) Science 296 1046
Lateral branching TEB invasionDichotomous branching
Mammary Development
3 wks 5 wks 11 wksnipple
lymph node
nipple
Luminal (Keratin 8/18)Myoepithelial (Keratin 5/14)
Mature Duct Terminal End Bud
Body cells
Cap cells
BCERC Epidemiology Study Populations
• Healthy girls age 6-8 yrs at time of recruitment
• California:– Bay area KPNC members
– Larry Kushi, PI, Division of Research, Kaiser Permanente Northern California
• Ohio:– Cincinnati-area school districts
– Frank Biro, PI, Cincinnati Children’s Hospital
• New York:– East Harlem neighborhood clinics
– Mary Wolff, PI, Mount Sinai School of Medicine
Methods• Food intake
• Physical activity
• Environmental exposures
• Medical and related history
• Psychosocial measures
• Demographics
• Anthropometry
• Biospecimens
• Tanner Staging
Puberty – Tanner Staging
Tempo (Pace, B2 → Menarche)
Tempo
3 y
2 y
3 y
Menarche12 y 13 y
Age (years)
9 10 11 12 13 14
B29 y 10 y
Cohort study of Young Girls’ Nutrition,
Environment & Transitions
A Project of the Bay Area Breast Cancer
and the Environment Research Center
CYGNET Study Population
• Born in and currently a member of Kaiser Permanente
• Resident at birth and currently of Marin County, San Francisco, and selected East Bay communities (e.g.,Richmond, El Cerrito, Berkeley, Oakland) in western Contra Costa and Alameda Counties
• Age 6 or 7 yrs at time of recruitment
KP San Francisco
KP San Rafael
KP DOR
Results to Date
Breast Maturation Status, age 7 yearsBCERP Puberty Studies, Biro et al., Pediatrics, 2010
GroupMSSM Cincinnati KPNC Total
B1 B2+ (%) B1 B2+ (%) B1 B2+ (%) B1 B2+ (%)
Black 77 31 (28.7) 75 34 (31.3) 75 26 (25.7) 233 71 (23.4)
Hispanic 117 25 (17.6) 10 1 (9.1) 79 10 (11.2) 206 36 (14.9)
Asian 4 0 (0.0) 40 1 (2.4) 44 1 (2.2)
White 184 29 (13.6) 179 13 (6.8) 363 42 (10.4)
Breast Maturation Status, age 8 yearsBCERP Puberty Studies, Biro et al., Pediatrics, 2010
GroupMSSM Cincinnati KPNC Total
B1 B2+ (%) B1 B2+ (%) B1 B2+ (%) B1 B2+ (%)
Black 83 11 (11.7) 54 58 (51.8) 55 24 (30.4) 109 82 (42.9)
Hispanic 97 60 (38.2) 8 4 (33.3) 78 18 (18.8) 283 82 (30.9)
Asian 4 0 (0.0) 34 6 (15.0) 38 6 (13.6)
White 156 57 (26.7) 152 12 (7.3) 308 69 (18.3)
Breast Development in the BCERP Puberty Studies (Biro, 2010) and PROS (Herman-Giddens, 1997)
Age 7 y Age 8 y
Father absence and breast development adjusted for BMI
Deardorff, et al., J Adol Health 2011
Income categoryB2 onset
AllRR (95% CI)
PH2 onset -AA
RR (95% CI)
Higher income, ≥$75,000/year 2.4 (1.2 – 4.9) 4.6(1.6-12.7)
Lower income, <$75,000/year 0.8 (0.5 – 1.2) 1.1(.5-2.6)
A Transdisciplinary Approach
METABOLOME
PROTEOME
TRANSCRIPTOME
GENOME
Policy
Neighborhoods
Workplace
Exercise
Smoking
Diet
TDS Conceptual Model
• Life-course approach• Multiple levels of analysis (social ecologic
model)• Stages of carcinogenesis• Must incorporate aims of constituent
investigators and collaborators• Demonstrate hypotheses• Predictive value
Life-course Approach
• Pre-natal
• Early childhood
• Pre-puberty
• Pregnancy
• Pre-menopause
• Menopause
• Post-menopause
Levels of Analysis
• Gene
• Cell
• Tissue/Organ
• Individual
• Family
• Neighborhood/City
• Society
Dissemination Activities
• Community meetings - bidirectional exchange (e.g., Town Halls, Tea Talks)
• Fact sheets on chemical exposures and puberty
• Communication (e.g., videos)
• Recruitment and retention
• Evaluation
• Hands-on Laboratory Training for Advocates
• Modeling Breast Cancer and the Environment Report
• DVD “Of Mice and Women”
• DVD “The Breast Biologues”
COTC Collaborations with Biology
Of Mice and Women: Modeling Breast Cancer and the Environment
An innovative educational tool to engage the community on why mouse models are used in breast cancer research
Developed by the Bay Area Breast Cancer and Environment Research Center, Community Outreach and Translation Core in partnership with Dr. Mary Helen Barcellos-Hoff, PhD, co-investigator, Project 1
The Breast Biologues: A biology dialogue about breast cancer and the environment
A new education kit that explains how the breast develops and how exposures to potential cancer-causing chemicals at specific times during development might influence future breast cancer risk.
Developed by the Bay Area Breast Cancer and Environment Research Center, Community Outreach and Translation Core in partnership with Lori Schkufza, an animation consultant; the BABCERC basic science researchers: Dr. Zena Werb at University of California San Francisco, Dr. Paul Yaswen at Lawrence Berkeley National Laboratory, and Dr. Mary Helen Barcellos-Hoff at New York University Langone School of Medicine.
Target Populations1. Study Participants
– Recruitment and Retention • Newsletters, Community Meetings
– Returning Individual Level Results
COTC Collaborations with Epidemiology
2. Pediatricians– PARDNER grant: Partnerships for the Dissemination of
New Results.
COTC Collaborations with Epidemiology
3. Lay Public– Community
Participation• Town Hall
Meetings
• Resource Tables
• Presentations
– Public Health Messages
COTC Collaborations with Epidemiology
How can we create effective messages/tools/interventions that integrate
findings from genetic, cellular, animal and human studies?
Purpose:• To synthesize the BCERC biological, toxicologic, and
epidemiologic research results into integrated messages at appropriate education levels that can be broadly disseminated to affected communities
• To identify key messages integrating the body of peer reviewed research derived from the BCERC network
• To identify strategies for developing key messages for affected communities
• To develop a well designed dissemination plan for the key messages developed
Public Health Messages
Challenges:• Are findings from the laboratory relevant for human
populations?
• When are findings consistent enough to warrant dissemination?
• How can we evaluate the impact of the findings on “final” endpoints ?
• What messages do we want to prioritize for the lay public?
• How do findings translate so they have utility for members of the lay public?
Public Health Messages
FIN
top related