Breast Cancer at Hiroshima

and Nagasaki

P. ROSEN Hasbrouck

Laboratory,

University

of Massachusetts,

Amherst,

Massachusetts

01003, USA

Abstract - A calculation is made of the incidence of breast cancer at Hiroshima and Nagasaki using the dosimetry of Straume and Dobson. Gamma rays cause a mutation in a critical gene. Using a two hit theory, an estimate of the number of target cells and a time period of 24 years, an estimate of the probability of carcinogenesis is obtained which is in good agreement with observation.

Introduction

In a previous paper (l), I have tried to calculate the probability of leukemia at Hiroshima and Nagasaki. The data is obtained now by Straume and Dobson (2). Now I wish to apply a similar method to the calculation of the probability of breast cancer using the data in (2) obtained by (LLNL), the Lawrence Livermore National Laboratory. The new dosimetry (3) suggests that both cities are essentially the same. That is, most of the radiation is y radiation with decreased neutrons at Hiroshima and at Nagasaki. The neutron component is small but the R.B.E. is questionable. In detail (4), in Nagasaki, the free in air (FIA) kerma due to y rays is slightly less in DS 86 (the new dosimetry) than in T65D. In Hiroshima the FIA neutron kerma is reduced by a factor of 10 while y kerma is increased under DS 86 compared to T65D. This increase is offset by shielding (both structural and self shielding) which tends to reduce y dose to external organs (4). There exists uncertainty in R.B.E. for neutrons (2, 3). Although Gofman (5) and

Ldewe and Mendelsohn unity.

(6) use end R.B.E.

of

Method

First I convert incidence in cases per lo6 person years to probability by multiplying the time elapsed (24 years). These figures are listed in Table 1. Then I calculate the probability of Breast cancer incidence (cases per 106 woman years) in the two cities as f function of Table 1

Laurence Livermore National Lab estimates of dose to breast. The cases are those due to bomb radiation. Incidence

209

C&es 10’ woman yrs.

Dose to breast (rad)

0

0

100

50

200

100 200 300 400

650 600 700

210

MEDICAL HYPOTHESES

breast cancer as a function of dose. The time interval of 24 years is obtained from reference (7). I assume that there is a critical gene that is controlled by an operator repressor complex (like the lac operon), the operator is 20 B.P. long and cancer is initiated by a mutation there. Premutational repair is extremely good so that we require a two hit theory. The first hit affects repair (probably an endonuclease). The second hit affects the operator causing the iniation of cancer. I believe the critical gene affected is involved with mitosis. I take the mutation frequency to be approximately 2 x 10’ per rad (8) used before in Rosen (9). Not counting zero incidence, the probability of breast cancer is:

observed results. However, the data are age averaged. I have no method to calculate the effect of age which has been shown by Gofman (5) to be important. I would need to have mutation frequency vs. age data. The age effect is due to hormones and increased mitotic activity. Conclusion

An age averaged calculation of the probability of breast cancer at Hiroshima and Nagasaki can be accomplished by a two hit mutation theory due to y radiation. References 1. Rosen

p =

No

(2

10~~)~

x

Fr average

(‘-Oe&Eq. 1)

where No is the number of breast cells at risk = 272 gms x cells (lo), I is the immunological efficiency such that (1-I) = 25 (9). DY = 130 rad from rat breast (11). As for number of cells per gm we use Gofman (5) page 406 where there are 2.5 x lo8 cells per gm of tissue. Operator length is 20 B.P. and Laverage= 1000 B.P. By adding P to spontaneous probability (5 x 10x3) we obtain Table 2 which is the total probability of breast cancer at different doses. Table 2

Probability calculated vs. dose.

of breast

cancer

observed

and

3. 4.

5. 6. 7.

Dose (rad)

Probability (obs.)

Probability (talc.)

0 50 100 200 300 400

5 x 7.5 x 11 x 20.6 x 19.4 x 21.8 x

_ 7.2 15 23 24.6 18.9

lo-’ lo-’ 10-j 1O-3 1o-3 lo-’

8. x x x x x

lo-.’ lo-” lo-’ lo-’ lo-’

9. 10.

11.

Discussion

The calculated

2.

results compare

favorably

with

P. X-ray or y-ray leukemogenesis at Hiroshima and Nagasaki. Med. Hyp. 26: 16, 1988. Straume T, and Dobson L R. Implications of new Hiroshima and Nagasaki dose estimates: cancer risks and neutron RBE. Health Physics 41: 666, 1981. Hei T K, Hall E J, and Waldren C A. Mutation induction and relative biological effectiveness of neutrons in mammalian cells. Rad. Res. 115: 281, 1988. An Assessement of the New Dosimetrv for A-bomb Survivors. W. H. Elliot ed, Panel on- Reassessment of A-Bomb Dosimetry, Chairman Frederick Seitz. Advisory Committee on the Radiation Effects Research Foundation. Commission on Life Sciences. National Research Council. National Academy Press, Washington, D. C. 1987. Gofman J N. Radiation and Human Health. Sierra Club Books, San Francisco, 1981. Loewe W L, Mendelsohn E. Revised dose estimate at Hiroshima and Nagasaki. Health Physics 41: 663, 1981. Beebe G G, Kato H, and Land C E. Studies of the mortality of A-bomb survivors-6 mortality and radiation dose 19561974. Rad. Res. 75: 138, 1978.Abrahamson S. Bender M A. Coneer A D. Wolf S. Uniformity of radiation induced mutation raies among different species. Nature 245: 460, 1973. Rosen P. X-radiation carcinogenesis in humans, Med. Hyp. 16: 33, 1985. US-Japan Joint Reassessment of Atomic Bomb Radiation Disimetry in Hiroshima and Nagasaki Vol. 1. N. C. Roesch. ed. Radiation Effects Research Foundation. Hiroshima 732, Japan, 1987. Gould M N, Cliften K H. The survival of rat mammary gland cells. Int. J. Rad. Oncol. and Biol. Phys. 4: 629, 1978.