Planning Towards The BEIR VIII Report

Transcription

1 Planning Towards The BEIR VIII Report WHAT IS NEW AND WHAT IS COMING NATIONAL ACADEMY OF SCIENCES MONDAY, NOVEMBER 17, 2014 SCOTT DAVIS, PHD

2 Chernobyl: April 26, 1986

3 Two New Studies of Exposures From Chernobyl A Brief Overview Population-based case-control studies of thyroid cancer and breast cancer Funded by NCI as 5-year R01 grants Conducted in the Bryansk Oblast of the Russian Federation Made possible by several years of building infrastructure and doing small feasibility studies. Have now developed the capability of doing all aspects of an epidemiological study

4 Region Included in Both Studies

5 Thyroid Case-Control Study: Feasibility Phase Case Definition Identified From Bryansk Cancer Registry Born Before April 26, 1986 Less Than Age 20 At Time of Accident Present in One of Eight Most Highly Contaminated Raions on April 26, 1986 Diagnosed Before October, 1997

6 Region Included in Both Studies

7 Findings From The Feasibility Study

8 Summary Of Feasibility Phase Population-Based Study Focused On Persons Who Were Young at the Time of Exposure Although based on small numbers, results indicate a large and significant increase in risk associated with radiation dose Risk estimates based on individual thyroid radiation dose estimation

9 Thyroid Case-Control Study Expansion Cases from entire Bryansk Oblast Diagnoses through August 1998 Same methods to identify cases Same methods to identify and match controls Same data collection and dosimetry methods

10 Thyroid Cancer - Cases Bryansk Cancer Registry Between 10 and 50 years old ATA Diagnosis: 2001 Resident of Bryansk Oblast: Current, ATA, At Diagnosis Confirmed Diagnosis: 4 Russian Pathologists

11 Case Diagnostic Review Independent Team Of Pathologists Initial Review in Russia Obninsk (Lushnikov, Abrosimov) Bryansk (Troshin) Moscow (Frank) Met Together For Joint Review Professor Dillwyn Williams (Cambridge)

12 Thyroid Cancer - Controls State Medical Dosimetry Registry Or Polyclinic Records Matched to Cases (2:1): Raion of Residence ATA Type of Settlement Calendar Year of Birth

13 Oncodispensary Records

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15 Data Collection Personal Interview (Home Visit) Dosimetry Questionnaire Medical History Other Radiation Exposures Family History Medical Record Review/Abstraction

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17 Thyroid Dose Estimation Dose Reconstruction Approach I-131 Measurements in Thyroid Measurements of Local Parameters (Settlements) Data Collection For Current Study Individual Dosimetry Interview mostly mothers food and milk consumption patterns Physical Sample Collection at Home Dose Rate Measurements at Home

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24 NIH-Funded Study Of Thyroid Cancer In Bryansk Primary Purposes Investigate whether specific markers of genetic change (e.g. tyrosine kinase expression, ret/ptc mutations) are associated with individual radiation dose Investigate whether age-at-exposure dependent radiation dose-response differs according to presence or absence of molecular markers Investigate whether molecular markers are associated with clinical outcome

25 Cases and Controls Total Number In The Study Cases 252 Controls 252 Cases By Gender Males 49 Females 203

26 Molecular studies are still in progress Preliminary Summary Population-Based Study Focused On Persons Who Were Age 0-50 at the Time of Exposure Results confirm earlier studies of a large and significant increase in risk associated with radiation dose Risk appears to be similar for males and females, and for all ages at exposure Risk estimates based on individual thyroid radiation dose estimation

27 Breast Cancer Case-Control Study Same design as thyroid studies (same sources of cases and controls, and same procedures) Same funding source (NCI) and length of award (five years) Added a significant lab component Focus on DNA repair genes: how they are altered in radiationrelated breast cancer Inadequate DNA repair results in tumors with features similar to tumors in BRCA1 carriers Will enroll approximately 500 cases and 500 controls Will collect fresh frozen tissue, saliva and blood STATUS: Data and sample collection is complete; dosimetry is being finalized and dose response analyses will begin shortly

28 Laboratory Aims Investigate whether the association between breast cancer and exposure to ionizing radiation differs according to: estrogen and progesterone receptor status genomic loss and gain (loss of heterozygosity (LOH) and gene amplification) gene silencing alterations (allelic loss and methylation) in 14 selected DNA repair genes Investigate whether the radiation dose response differs for subsets of breast cancers defined by these features.

29 Thank You For Your Attention