Epidemiology data for low-linear energy transfer radiation

Epidemiological studies of the health effects of low levels of ionizing radiation, in particular the incidence and mortality from various forms of cancer, have been carried out in different population groups exposed to such radiation. These have included survivors of the atomic bombings of Hiroshima and Nagasaki in 1945, workers at nuclear reactors, and medical patients treated with X-rays.

Life span studies of atomic bomb survivors

Survivors of the atomic bomb explosions at Hiroshima and Nagasaki, Japan have been the subjects of a Life Span Study (LSS), which has provided valuable epidemiological data.

The LSS population went through several changes:

1945 – There were some 93,000 individuals, either living in Hiroshima or Nagasaki, Japan.
1950 – An additional 37,000 were registered by this time, for a total of 130,000 LSS members.

However, some 44,000 individuals were censured or excluded from the LSS project, so there remained about 86,000 people who were followed through the study. There is a gap in knowledge of the earliest cancer that developed in the first few years after the war, which impacts the assessment of leukemia to an important extent and for solid cancers to a minor extent. Table 1 shows summary statistics of the number of persons and deaths for different dose groups. These comparisons show that the doses that were received by the LSS population overlap strongly with the doses that are of concern to NASA Exploration mission (i.e., 50 to 2,000 milliSieverts (mSv)).

*Table 1. Number of persons, Cancer Deaths, and Non-cancer Deaths for Different Dose Groups in the Life Span Study^[2]*
	DS86 Weighted Colon Dose, mSv
	Total	0-50	50-100	100-200	200-500	500-1,000	1,000-2,000	>2,000
No. Subjects	86,572	37,458	31,650	5,732	6,332	3,299	1,613	488
Cancer Deaths	9,335	3,833	3,277	668	763	438	274	82
Non-cancer Deaths	31,881	13,832	11,633	2,163	2,423	1,161	506	163

Figure 1 shows the dose response for the excess relative risk (ERR) for all solid cancers from Preston et al.^[1] Tables 2 and 3 show several summary parameters for tissue-specific cancer mortality risks for females and males, respectively, including estimates of ERR, excess absolute risk (EAR), and percentage attributable risks. Cancer incidence risks from low-LET radiation are about 60% higher than cancer mortality risks.^[3]

*Table 2. From Preston et al.:^[1] Tissue-specific Cancer Mortality Risk Summary Statistics (i.e., ERR, EAR, and Attributable Risks) for Females and Males, Respectively*
Site/System	Deaths (>0.005Sv)	ERR/Sv^a (90% CI)	EAR/10⁴PY^b -Sv^c (90%CI)	Attributable risk (%)^d
All solid cancer	4,884 (2,948)	0.63 (0.49; 0.79)	13.5 (7.4; 16.3)	9.2 (7.4; 11.0)
Oral cavity	42 (25)	-0.20 (<-0.3; 0.75)	-0.04 (<-0.3; 0.14)	-4.1 (<-6; 14)
Digestive System
Esophagus	67 (44)	1.7 (0.46; 3.8)	0.51 (0.15; 0.92)	22 (6.6; 42)
Stomach	1,312 (786)	0.65 (0.40; 0.95)	3.3 (2.1; 4.7)	8.8 (5.5; 12)
Colon	272 (786)	0.49 (0.11; 1.1)	0.68 (0.76; 1.3)	9.0 (4.3; 17)
Rectum	198 (127)	0.75 (0.16; 1.6)	0.69 (0.16; 1.3)	11.3 (2.6; 22)
Liver	514 (291)	0.35 (0.07; 0.72)	0.85 (0.18; 1.6)	6.2 (1.3; 12)
Gallbladder	236 (149)	0.16 (-0.17; 0.67)	0.18 (-0.21; 0.71)	2.6 (-2.9; 10)
Pancreas	244 (135)	-0.01 (-0.28; 0.45)	-0.01 (-0.35; 0.52)	-0.2 (-5.0; 7.6)
Respiratory System
Lung	548 (348)	1.1 (0.678; 1.6)	2.5 (1.6; 3.5)	16 (10; 22)
Female breast	272; (173)	0.79 (0.29; 1.5)	1.6 (1.2; 2.2)	24 (18; 32)
Uterus	518 (323)	0.17 (-0.10; 0.52)	0.44 (-0.27; 1.3)	2.7 (-1.6; 7.9)
Ovary	136 (85)	0.94 (0.07; 2.0)	0.63 (0.23; 1.2)	15 (5.3; 28)
Urinary System
Bladder	67 (43)	1.2 (0.10; 3.1)	0.33 (0.02; 0.74)	16 (0.9; 36)
Kidney	31 (21)	0.97 (<-0.3; 3.8)	0.14 (<-0.1; 0.42)	14 (<-3; 42)
Brain/CNS^d	17 (10)	0.51 (<-0.3; 3.9)	0.04 (<-0.02; 0.2)	11 (<0.05; 57)
^aERR/SV for age at exposure 30 in an age-constant linear ERR model; ^bExcess absolute risk per 10,000 persons per year; ^cAverage EAR computed from ERR model; ^dAttributable risk among survivors whose estimated dose is at least 0.005 Sv; CNS – central nervous system.

*Table 3. From Preston et al.:^[1] Tissue-specific Cancer Mortality Risk Summary Statistics 9 i.e., ERR, EAR, and Attributable Risks) for Males*
Site/System	Deaths (>0.005Sv)	ERR/Sv^a (90% CI)	EAR/10⁴PY^b -Sv^c (90%CI)	Attributable risk (%)^d
All solid cancer	4,451 (2,554)	0.37 (0.26; 0.49)	.6 (9.4; 16.2)	6.6 (4.9; 8.4)
Oral cavity	68 (37)	-0.20 (<-0.3; 0.45)	-0.12 (<-0.3; 0.25)	-5.2 (<-6; 11)
Digestive System
Esophagus	224 (130)	0.61 (0.15; 1.2)	1.1 (0.28; 2.0)	11.1 (2.8; 21)
Stomach	1,555 (899)	0.20 (0.04; 0.39)	2.1 (0.43; 4.0)	3.2 (0.07; 6.2)
Colon	206 (122)	0.54 (0.13; 1.2)	1.1 (0.64; 1.9)	12 (6.9; 21)
Rectum	172 (96)	-0.25 (<-0.3; 0.15)	-0.41 (<-0.4; 0.22)	-5.4 (<-6; 3.1)
Liver	722 (408)	0.59 (0.11; 0.68)	2.4 (1.2; 4.0)	8.4 (4.2; 14)
Gallbladder	92 (52)	0.89 (0.22; 1.9)	0.63 (0.17; 1.2)	17 (4.5; 33)
Pancreas	163 (103)	-0.11 (<-0.3; 0.44)	-0.15 (<-0.4; 0.58)	--1.9 (<-6; 7.5)
Respiratory System
Lung	716 (406)	0.48 (0.23; 0.78)	2.7 (1.4; 4.1)	9.7 (4.9; 15)
Urinary System
Bladder	82 (56)	1.1 (0.2; 2.5)	0.7 (0.1; 1.4)	17 (3.3; 34)
Kidney	36 (18)	-0.02 (<-0.3; 1.1)	-0.01 (-0.1; 0.28)	-0.4 (<-5; 22)
Brain/CNS^d	14 (9)	5.3 (1.4; 16)	0.35 (0.13; 0.59)	62 (23; 100)
^aERR/SV for age at exposure 30 in an age-constant linear ERR model; ^bExcess absolute risk per 10,000 persons per year; ^cAverage EAR computed from ERR model; ^dAttributable risk among survivors whose estimated dose is at least 0.005 Sv; CNS – central nervous system.

Other human studies

The BEIR VII Report^[2] contains an extensive review of data sets from human populations, including nuclear reactor workers and patients who were treated with radiation. The recent report from Cardis et al.^[4] describes a meta-analysis for reactor workers from several countries. A meta-analysis at specific cancer sites, including breast, lung, and leukemia, has also been performed.^[2] These studies require adjustments for photon energy, dose-rate, and country of origin as well as adjustments made in single population studies. Table 4 shows the results that are derived from Preston et al.^[5] for a meta-analysis of breast cancer risks in eight populations, including the atomic-bomb survivors. The median ERR varies by slightly more than a factor of two, but confidence levels significantly overlap. Adjustments for photon energy or dose-rate and fractionation have not been made. These types of analysis lend confidence to risk assessments as well as showing the limitations of such data sets.

Of special interest to NASA is the dependence on age at exposure of low-LET cancer risk projections. The BEIR VII report prefers models that show less than a 25% reduction in risk over the range from 35 to 55 years, while NCRP Report No. 132^[6] shows about a two-fold reduction over this range.

Table 4. Results from Meta-analysis of Breast Cancer from Eight Population Groups, Including the Life Span Study of Atomic Bomb Survivors and Several Medical Patient Groups Exposed to X Rays, as described in Preston et al.^[5]
Cohort	Reference age for the ERR/Gy estimate	ERR/Gy^a	Percentage change per decade increase in age at exposure	Exponent of attained age	Background SIR^b
LSS	attained age 50	2.10 (1.6; 2.8)	Not included^b	-2.0 (-2.8; -1.1)	1.01 (0.9; 1.1)
TBO	attained age 50	0.74 (0.4; 1.2)	Not included	-2.0 (-2.8; -1.1)	0.96 (0.7; 1.2)
TBX	attained age 50	0.74 (0.4; 1.2)	Not included	-2.0 (-2.8; -1.1)	0.73 (0.6; 0.9)
THY	attained age 50	0.74 (0.4; 1.2)	Not included	-2.0 (-2.8; -1.1)	1.05 (0.7; 1.5)
BBD	age at exposure 25	1.9 (1.3; 2.8)	-60% (-71%; -44%)	Not included^c	0.98 (0.8; 1.2)
APM	all ages	0.56 (0.3; 0.9)	Not included	Not included	1.45 (1.1; 1.8)
HMG	all ages	0.34 (0.1; 0.7)	Not included	Not included	1.07 (0.8; 1.3)
HMS	all ages	0.34 (0.1; 0.7)	Not included	Not included	1.05 (0.9; 1.2)
^a C.I.'s within parentheses; ^bSIR = standardized incidence ratio; ^c"Not included" means that the risk is assumed not to vary with age at exposure (attained age).

References

^ ^a ^b ^c ^d Preston, DL; Shimizu, Y; Pierce, DA; Suyama, A; Mabuchi, K (October 2003). "Studies of mortality of atomic bomb survivors. Report 13: Solid cancer and noncancer disease mortality: 1950-1997" (PDF). Radiation Research. 160 (4): 381–407. Bibcode:2003RadR..160..381P. doi:10.1667/RR3049. PMID 12968934. S2CID 41215245. Archived from the original (PDF) on 28 October 2011. Retrieved 5 July 2012.
^ ^a ^b ^c Committee to Assess Health Risks from Exposure to Low Levels of Ionizing Radiation; National Research Council of the National Academies (2006). Health risks from exposure to low levels of ionizing radiation BEIR VII, Phase 2 ([Online-Ausg.] ed.). Washington, D.C.: National Academies Press. ISBN 978-0-309-53040-8. Retrieved 1 October 2013.
^ Preston, DL; Ron, E; Tokuoka, S; Funamoto, S; Nishi, N; Soda, M; Mabuchi, K; Kodama, K (July 2007). "Solid cancer incidence in atomic bomb survivors: 1958-1998". Radiation Research. 168 (1): 1–64. Bibcode:2007RadR..168....1P. doi:10.1667/RR0763.1. PMID 17722996. S2CID 7398164.
^ Cardis, E; Vrijheid, M; Blettner, M; Gilbert, E; Hakama, M; Hill, C; Howe, G; Kaldor, J; Muirhead, CR; Schubauer-Berigan, M; Yoshimura, T; Bermann, F; Cowper, G; Fix, J; Hacker, C; Heinmiller, B; Marshall, M; Thierry-Chef, I; Utterback, D; Ahn, YO; Amoros, E; Ashmore, P; Auvinen, A; Bae, JM; Bernar, J; Biau, A; Combalot, E; Deboodt, P; Diez Sacristan, A; Eklöf, M; Engels, H; Engholm, G; Gulis, G; Habib, RR; Holan, K; Hyvonen, H; Kerekes, A; Kurtinaitis, J; Malker, H; Martuzzi, M; Mastauskas, A; Monnet, A; Moser, M; Pearce, MS; Richardson, DB; Rodriguez-Artalejo, F; Rogel, A; Tardy, H; Telle-Lamberton, M; Turai, I; Usel, M; Veress, K (April 2007). "The 15-Country Collaborative Study of Cancer Risk among Radiation Workers in the Nuclear Industry: estimates of radiation-related cancer risks". Radiation Research. 167 (4): 396–416. Bibcode:2007RadR..167..396C. doi:10.1667/RR0553.1. PMID 17388693. S2CID 36282894.
^ ^a ^b Preston, DL; Mattsson, A; Holmberg, E; Shore, R; Hildreth, NG; Boice JD, Jr (August 2002). "Radiation effects on breast cancer risk: a pooled analysis of eight cohorts". Radiation Research. 158 (2): 220–35. Bibcode:2002RadR..158..220P. doi:10.1667/0033-7587(2002)158[0220:reobcr]2.0.co;2. JSTOR 3580776. PMID 12105993. S2CID 30505427.
^ NCRP (2000). NPRC Report No. 132: Recommendations of dose limits for low Earth orbit. Bethesda, MD: NCRP. Archived from the original on 4 October 2013. Retrieved 5 July 2012.