long island
Post on 01-Jan-2016
84 Views
Preview:
DESCRIPTION
TRANSCRIPT
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 1992-1996SEER Nassau Suffolk
Incidence 109.5 117.8 113.6Mortality 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
LIBCSPPrimary 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 AimsWhether 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
LIBCSPAdditional 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 Cancer Cases • 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-Based Controls
• 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%
LIBCSP Case-Control Study
Random sample of long-term (15 yr) residents:Interview-home samples
Cases Controls
Dust 84% 83%
Water 94% 94%
Soil 94% 94%
LIBCSP Molecular Epidemiology StudiesBiologic 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 significantBreast 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 smoking Adjacent Tissue Tumor Tissue
Never 5.770.60 20 5.330.71 57 Past/former 5.950.50 25 5.430.83 65 Current 6.200.43 10 5.370.80 26
p=0.04a p=0.68a
Passive smoking Never 5.520.83 5 5.640.71 15 Past/former 5.970.50 43 5.370.77 108 Current 6.030.49 6 5.280.86 23
p=0.14a p=0.19a
Active and passive smoking Never either 4.630.14 2 5.240.58 7 Ever passive only 5.900.48 18 5.340.73 50 Ever active only 6.110.25 3 5.990.66 8 Ever both 6.020.51 31 5.360.82 81
p=0.03a p=0.84a
a p value for linear trend
Genes Environment
Interindividual Variation
Cancer
Carcinogen metabolism Chemicals
Estrogen metabolism Radiation
DNA Repair Viruses
Exon 23 Polymorphism in XPD and Breast Cancer Risk
Genotype Cases Controls OR(95%CI)
N(%) N(%)
Lys/Lys (AA) 387 453 1
Lys/Gln (AC) 513 498 1.22(1.01-1.46)
Gln/Gln (CC) 153 151 1.18(0.91-1.53)
Lys/Gln+Gln/Gln 666 649 1.21(1.01-1.44)
Multivariate-adjusted ORs for Risk Factors Stratified by XPD Status
Genotype PAH-DNA
Nondetect <Median >Median
AA 1 1 1
AC 1.25(0.83-1.86) 1.01(0.71-1.44) 1.22(0.85-1.76)
CC 0.91(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 Former Current
AA 1 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
GG 1
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-UpBreast 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
CollaboratorsUNC: MD Gammon (PI), P Abrahamson, R Cleveland,
S White, K McCullough, M Gaudet, K Conway, R Millikan,S Steck-ScottColumbia: 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 AmbrosoneStonybrook: G Kabat, E O’LearyNIH: Obrams (NCI), G Coleman (NIEHS), E
Heineman (NCI)Westat: C Maffeo, P Montalvan
top related