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Long Island. Long Island residents concerned about : DDT for control of gypsy moths and mosquitoes Other pesticides used on farmlands Groundwater contamination Air pollution (major roads, airports) Electromagnetic fields Chemical waste. Long Island. Breast Cancer Rates

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Long Island

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Long Island

Long Island residents concerned about:

  • DDT for control of gypsy moths and mosquitoes

  • Other pesticides used on farmlands

  • Groundwater contamination

  • Air pollution (major roads, airports)

  • Electromagnetic fields

  • Chemical waste


Long Island

Breast Cancer Rates

(per 100,000 women, age-standardized to1970 U.S. population)

1997 1992-1996

SEERNassauSuffolk

Incidence109.5117.8113.6

Mortality 27.2 30.6 31.1

Source: http://www.health.state.ny.us/nysdoh/cancer/volume1.htm

SEER - Surveillance, Epidemiologu and End Results ~15% of US population


Long Island Breast Cancer Study Project

NCI and NIEHS sponsored group of ten studies undertaken in response to federal legislation (Public Law 103-43)

  • The cornerstone project, LIBCSP, is a large population-based study of 3000 women


LIBCSP

Primary Aims

Determine whether breast cancer is associated with:

  • Organochlorine compounds (DDT/DDE, PCBs, chlordane, dieldrin) as measured in blood

  • Polycyclic aromatic hydrocarbon (PAH)-DNA adducts


LIBCSP Other Aims

Whether breast cancer is associated with:

  • Lifestyle

    • alcohol, body size, recreational physical activity, occupational physical activity

  • Diet

    • PAH-related foods, alcohol, isoflavones, estrogen-metabolite related foods, folate, phytoestrogens, insulin-related foods, brassica veggies

  • Early life exposures

    • DES, preeclampsia

  • HRT and other factors among the elderly

  • Family History of Cancer

  • Medical History

    • NSAIDS


LIBCSP

Additional Environmental Study Aims

  • Questionnaire-assessed exposures

    • self-reported pesticide use

    • environmental tobacco smoke (ETS)

    • home appliance exposure to electromagnetic fields (EMF)

    • occupation

    • medical ionizing radiation

  • Historical exposures assessed by geographic modeling

    • long-term PAH exposure

      • Model validated against soil sample measures taken from the home

  • Exposure assessment based on home samples

    • in-home exposure to PAH and organochlorines in dust samples

    • chlorinated and carbamated pesticides, and metals in drinking water

  • Biologic samples

    • urinary estrogen metabolites

      • ratio of 16alpha-hydroxyestrone to 2-hydroestrone


Population-Based Breast CancerCases

Eligibility criteria

newly diagnosed 1996-1997

resident of Nassau or Suffolk county

no age restrictions

speaks English

Identification protocol

daily contact with 33 hospitals on LI and NYC

diagnosis confirmed by MD

N = 1508

82% completed interviews

Response varied by age:< 65yrs = 89%, 65yrs = 72%


Population-BasedControls

Eligibility criteria

resident of Nassau or Suffolk county

no personal history of breast cancer

speaks English

frequency-matched on age to expected distribution of cases

Identification protocol

Random digit dialing among women under age 65 years

Health Care Financing and Administration for >65 years

N = 1556

63% completed interviews

Response varied by age:< 65 yrs=76%, 65 yrs=43%


Random sample of long-term (15 yr) residents:

Interview-home samples

CasesControls

Dust 84%83%

Water 94%94%

Soil 94%94%

LIBCSP Case-Control Study


LIBCSP Molecular Epidemiology Studies

Biologic Specimens Available:

  • Urine (n = 1400 cases and 1300 controls)

  • Blood (n = 1100 cases and 1100 controls)

  • DNA isolated from blood donations

    (n = 1100 cases and 1100 controls)

  • Archived tumor blocks (n = 975 cases)


Results of LIBCSP in Relation to Known Risk Factors

Protective Beginning menstruating at an older age

Having children

Increases with number of children

Having a first child at a younger age

Breast feeding

Risk Factor Higher body mass index is a risk factor

Smoking and alcohol consumption are not significant

Breast Cancer Res Treat 74: 235, 2002


Environmental Chemicals and Risk for Breast Cancer in the LIBCSP

No relationship with blood levels of organochlorine compounds measured - DDE, DDT, PCBs, dieldrin, chlordane

High PAH-DNA damage in blood cells indicated small (50%) but statistically significant increase in risk-but no dose-response [Results duplicated in remaining samples]


Immunohistochemical Detection of 4-ABP-DNA in Breast Adjacent Nontumor Tissues

4ABP-DNA higher in smokers compared to nonsmokers


4-ABP-DNA (log transformed staining intensity) in Tumor and Normal Adjacent Tissue

Active smokingAdjacent TissueTumor Tissue

Never5.770.60205.330.71 57

Past/former5.950.50255.430.83 65

Current6.200.43105.370.80 26p=0.04ap=0.68a

Passive smoking

Never5.520.83 55.640.71 15

Past/former5.970.50435.370.77108

Current6.030.49 65.280.86 23

p=0.14ap=0.19a

Active and passive smoking

Never either4.630.14 25.240.58 7

Ever passive only5.900.48185.340.73 50

Ever active only6.110.25 35.990.66 8

Ever both6.020.51315.360.82 81

p=0.03ap=0.84a

a p value for linear trend


Carcinogen metabolism Chemicals

Estrogen metabolism Radiation

DNA Repair Viruses

Genes Environment

Interindividual Variation

Cancer


Exon 23 Polymorphism in XPD and Breast Cancer Risk

GenotypeCasesControlsOR(95%CI)

N(%)N(%)

Lys/Lys (AA)3874531

Lys/Gln (AC)5134981.22(1.01-1.46)

Gln/Gln (CC)1531511.18(0.91-1.53)

Lys/Gln+Gln/Gln6666491.21(1.01-1.44)


Multivariate-adjusted ORs for Risk Factors Stratified by XPD Status

Genotype PAH-DNA

Nondetect<Median>Median

AA111

AC1.25(0.83-1.86)1.01(0.71-1.44)1.22(0.85-1.76)

CC0.91(0.52-1.62)1.05(0.64-1.74)1.61(0.99-2.63)


Multivariate-adjusted ORs for Risk Factors Stratified by XPD Status

Active Smoking

Never FormerCurrent

AA1 1 1

AC 0.89(0.67-1.19) 1.56(1.12-2.16) 1.25(0.80-1.97)

CC 0.87(0.57-1.32) 1.16(0.75-1.81) 1.97(1.02-3.81)


Myeloperoxidase Genotype, Dietary Antioxidants and Breast Cancer Risk

G463A variant-in promoter region-G allele higher transcriptional activation

Among premenopausal women

GG1

GA 0.92(0.63-1.33)

AA 0.42(0.21-0.84)

GA+AA+high fruits/veg0.33(0.13-0.88)

Ahn, Ambrosone et al


LIBCSP Molecular Epidemiology Studies(projects as of 10/03)

Urinary Markers:

  • Estrogen metabolites, isoprostanes,isothiocyanates

    Blood Markers:

  • Exposure Markers

    • PAH-DNA adducts, oxidative DNA damage, organochlorine compounds, insulin (among controls)

  • Genetic Markers

    • polymorphisms in estrogen,folate and carcinogen metabolism,DNA repair, oxidative stress , estrogen receptor alpha and beta genes, IGF, cyclin D

      Tumor Markers:

  • Tissue - PAH-DNA, 4-ABP-DNA, p53 protein expression, p53 mutations, cyclin D1 and HER-2/neu overexpression

  • Blood - antibodies to p53, HER-2/neu protein


LIBCSP Follow-Up

Breast Cancer Cases

  • Determine case vital status, change of address

  • Primary exposures of interest are measures:

    • assessed at baseline case-control study, and

    • during the follow-up interview

  • Re-interview case participants or proxy at 5-year follow-up

    • One-hour telephone interview to determine medical treatment for initial cancer, and changes in:

      • residence, occupation, use of pesticides and other contaminants, appliance use, alcohol use, passive and active smoking, body size, physical activity, medical hx, hormone use, complementary and alternative medicine (CAM) use

    • Self-administered FFQ

  • Collect medical records

  • Determine outcome status

    • NYS Tumor Registry, NDI, respondent, medical record


LIBCSP: Companion Projects

  • Geographic Information System (GIS)

    • National Cancer Institute

      • Mapped layers of historical exposure data from multiple sources (EPA)

      • -Mapped cancer data from NYS Tumor registry, conserving patient privacy

    • Use as an estimate of historical exposures, particularly for compounds for which biomarkers are not currently feasible

    • May be useful for exploratory or hypothesis-generating analyses

    • Access on line

      • lay public vs. scientific researchers


LIBCSP: Companion Projects

  • Electromagnetic Fields (EMF)

    • SUNY at Stony Brook (PI: C Leske)

      • Recontacted long-term residents of case-control interview

        • More detailed interview on occupational and residential EMF exposures

        • In-home spot and 24-hour measures with EMDEX meter

        • Wire Coding

    • May affect production of melatonin

      • inversely related to biologically available endogenous estrogen levels


LIBCSP

Collaborators

UNC:MD Gammon (PI), P Abrahamson, R Cleveland, S White, K McCullough, M Gaudet, K Conway, R Millikan,S Steck-Scott

Columbia:RM Santella, AI Neugut, S Stellman, MB Terry, R Senie, B Levin, J Jacobson, H Hibshoosh

Mt. Sinai: MS Wolf, M Hatch, SL Teitelbaum, JA Britton, J Chen, C Ambrosone

Stonybrook: G Kabat, E O’Leary

NIH:Obrams (NCI), G Coleman (NIEHS), E Heineman (NCI)

Westat:C Maffeo, P Montalvan


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