Community Participation in Cancer Discovery Research ... Community Participation ¢â‚¬¢ Community Based

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  • Community Participation in Cancer Discovery Research: Linking Biology,

    Cancer Disparities, and Dissemination

    Robert A. Hiatt

    UCSF Helen Diller Family Comprehensive Cancer Center

    July 13, 2011 Bethesda, 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 Rates age-standardized rates, 1988-1992

    From Parkin, et al., IARC, 1997

    Cases/100,000 p-yrs

  • Variation in Breast Cancer Rates, Japanese age-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% CI Age at menarche ≥15 vs. 30 vs. ≤20 y 1.46 (1.22-1.75) Education >HS vs.

  • 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 Development at Tanner Stage 2 or Greater by Age and Race

    Herman-Giddens et al., Pediatrics, 1997

  • Height & Breast Cancer Pooled Analysis, Cohort Studies of Diet & Breast Cancer

    Cohort

    Re la

    ti ve

    R is

    k, H

    ei gh

    t ( m

    ) ≥1

    .6 8

    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 Milestones NHLBI 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 Puberty PI: Lawrence Kushi, ScD, KP/DOR

    PI: Robert A. Hiatt, MD, PhD, UCSF CCC

    Community Outreach and Translation Core PI: Janice Barlow, RN, Zero Breast Cancer

  • Breast Cancer and the Environment Research Centers (BCERCs)

    Cincinnati Children’s HospitalUCSF LBNL

    Michigan State University

    University of Cincinnati

    Mount Sinai School of Medicine

    Fox Chase Cancer Center

    Kaiser Permanente

    University of Alabama

    NIEHS

    NCI

    Zero Breast Cancer

    Funding Agencies

    BCERC Prime Institutions

    Collaborating Institutions

    Roswell Park Cancer Institute

    University of MichiganCalifornia Departmentof Health Services

    Marin County DHHS

  • Project 1 - Specific Aims

    Specific Aim 1: Determine the alterations in the mammary microenvironment and the mammary cells in normal and cancer prone mice in vivo during prenatal development, pubertal branching morphogenesis, pregnancy and aging.

    Specific Aim 2: Determine the effects of exposure to prototypical environmental stressors during prenatal development, pubertal branching morphogenesis, pregnancy and aging on the mammary gland in normal and cancer prone mice in vivo

    Specific Aim 3: Determine the effects of environmental agents implicated from studies in Project 2 on regulating the mammary microenvironment of mammary cells 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 invasion Dichotomous 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

    Menarche 12 y 13 y

    Age (years)

    9 10 11 12 13 14

    B2 9 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 years BCERP Puberty Studies, Biro et al., Pediatrics, 2010

    Group MSSM 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 years BCERP Puberty Studies, Biro et al., Pediatrics, 2010

    Group MSSM 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 category B2 onset

    All RR (95% CI)

    PH2 onset - AA

    RR (95% CI)

    Higher income,