EPA Radiogenic Cancer Risk Projections for the U.S. Population

Michael Boyd Radiation Protection Division U.S. Environmental Protection Agency 2011 OAS Annual Meeting Richmond, VA August 24, 2011

EPA’s Risk Estimates

• Old “Blue Book” published (1994) • Addendum on uncertainties with some revisions (1999) • FGR-13: radionuclide specific estimates (1999) 2

NAS BEIR VII Rept. (2006)

• Co-sponsored by EPA and several other Federal agencies • Developed models for estimating low dose, low-LET radiogenic cancer risk as a function of: – Dose – Cancer site – Sex – Age-at-exposure – Age-at-diagnosis (death) • Developed quantitative uncertainty distributions 3

BEIR VII Treatment of Low Dose Issue

Endorsed LNT:

“…the balance of evidence from epidemiologic, animal and mechanistic studies tend to favor a simple proportionate relationship at low doses between radiation dose and cancer risk.”

Derived a DDREF of 1.5

for solid cancers based on a “Bayesian” analysis of epidemiological and radiobiological data 4

BEIR VII Risk Models

• • Most models derived from Japanese Life Span Study (LSS)

incidence

data • Breast and thyroid risks from pooled analyses of medical and LSS cohorts Most solid cancer risk models were assumed to have the same age and temporal dependency • Two models for most solid cancers, EAR and ERR: – The excess absolute risk (EAR) adds to the baseline cancer incidence or mortality rate – The excess relative risk (ERR) multiplies the baseline cancer rate 5

Cancer Risk Coefficients

•

Excess absolute risk (EAR):

rate of radiogenic cancers per unit dose • Excess relative risk (ERR): fractional increase in cancer rate per unit dose; i.e., radiogenic cancer rate per unit dose divided by baseline rate in the population 6

EPA Modifications and Additions to BEIR VII Approach

• • • • • • • Additional cancer sites (bone, kidney, skin) High-LET (α-particle) risk estimates Stationary population Weighted arithmetic mean of ERR & EAR estimates rather than geometric mean Breast cancer analysis Risk estimate for prenatal exposures Expanded uncertainty analysis 7

MALES

Risk (Gy

-1

) from Uniform, Whole-Body Irradiation

INCIDENCE 2011 1999 MORTALITY 2011 1999 9.6x10

-2 6.5x10

-2 4.7x10

-2 4.6x10

-2 FEMALES 1.4x10

-1 1.0x10

-1 6.9x10

-2 6.8x10

-2 ALL 1.2x10

-1 8.5x10

-2 5.8x10

-2 5.7x10

-2

8

0.4

Age-Dependence of Risk from Whole-Body Irradiation

0.3

0.2

Incidence

——

Mortality – – – – Incidence ——— Mortality ——— 0.1

0 0 20 40 60

Age at exposure

80 9

Life-Table Calculations

Age- and Sex-Specific Survival Functions

• •

Life-table calculation:

corrects for competing causes of death

Survival function, S(a,a

e

):

probability of surviving to age a, conditioned on being alive at age of exposure, a

e

• •

r(a,a

e

) = f(D) g[a,a

e ,r 0

(a)] S(a,a

e

)

Lifetime Attributable Risk

due to an exposure at age a

e

: LAR (a

e

) = ∑ r(a,a

e

) • Population risk: ∑ N(a

e

) LAR (a

e

) 10

Stationary Population

• Age distribution constant – – # births = # deaths, each year N(a) = N 0 S( 0 ,a) • Risk per Gy for (small)

acute

that for

chronic

exposure = low dose rate exposure •

Stationary population

population ===> “older” than the U.S. estimated radiogenic cancer

risk is lower

11

Averaging Model Projections

• Weighted Arithmetic Mean AM = w(EAR) + (1-w)(ERR) • Weighted Geometric Mean log GM = w log (EAR) + (1-w) log (ERR) • GM ≤ AM • For most sites, BEIR recommended GM and w = 0.3, GM = (EAR) .3

(ERR) .7

Exceptions – Lung (wts. reversed), Thyroid, Breast 12

LAR Projections for Incidence ( x 10 -4 Gy -1 ) Cancer Site Stomach Colon Lung Breast Leukemia Other (Skin) Total Males 62 146 130 — 92 525 (182) 955 Females 75 92 308 289 69 518 (96) 1351 Sex-Averaged 68 119 220 146 80 522 (138) 1155

13

Other Revisions & Extensions to BEIR VII

• • •

Thyroid:

Model primarily based on NCRP Thyroid Report (NCRP No. 159)

Skin:

Model projection for BCC but not included in total incidence estimate •

Alpha-particles

– – For most sites, RBE=20 For leukemia, RBE=2

Bone cancer

– – Model based on studies of patients injected with 224 Ra Low-LET estimate derived assuming that RBE=20 14

Major Sources of Uncertainty

• Sampling errors • Transport of risk from the LSS cohort to the U.S. population • DDREF • Age/temporal dependence 15

Uncertainty in Low-Dose “Extrapolation”

BEIR VII/EPA implicitly assumes: (1) LQ dose-response: R = α D +

β D 2

(2)

β/

α, DDREF same for all solid cancers 95% CI on DDREF then turns out to be ≈ a factor of 2, up or down 16

Cancer Site Stomach Colon Liver Lung Breast Prostate Thyroid Leukemia Total Uncertainties Projection (per 10 4 person-Gy) 68 119 30 220 146 44 44 80 1180 Uncertainty Interval (90%) (9, 220) (42, 220) (6, 94) (83, 420) (70, 290) (0, 200) (15, 140) (29, 160) (560, 2130)

17

Other Data Pertaining to Low Dose Risks I. Radiobiology

• Experiments indicate novel phenomena not easily reconciled with standard paradigm for radiation carcinogenesis – Adaptive response, bystander effect, genomic instability, etc.

– Mostly based on cellular studies, inconsistency among laboratories – significance for human carcinogenesis unclear – May produce increased as well as decreased risks 18

Other Data Pertaining to Low Dose Risks II. Epidemiology

• Epidemiological data on cohorts receiving fractionated or chronic exposures show excess risks, generally consistent with a DDREF of about 1. –

Fractionated:

Multiple fluoroscopies (breast cancer) Scoliosis patients (breast cancer) Tinea capitis patients (thyroid) –

Chronic:

British nuclear workers (leukemia, solid cancers) Chernobyl liquidators (leukemia) Techa R. Cohort (leukemia, solid cancers) Taiwanese apartment dwellers (leukemia) Semipalatinsk test-site residents (solid cancers) 19

Future

Plans

• • •

New “Blue Book”:

Available on RPD web-site at www.epa.gov/radiation

Addendum on RBE

for low energy electrons and photons to be published by ORNL – Important for 3 H betas, medical X-rays, & perhaps certain external radionuclide exposure situations – NCRP committee also working on such a report

New Federal Guidance Report

on risks from external and internal radionuclide exposures – Replace FGR-13 – Use new risk models in combination with latest ICRP dosimetry 20