Spaceflight radiation carcinogenesis

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https://en.wikipedia.org/wiki/Spaceflight_radiation_carcinogenesis 

The Phantom Torso, as seen here in the Destiny laboratory on the International Space Station (ISS), is designed to measure the effects of radiation on organs inside the body by using a torso that is similar to those used to train radiologists on Earth. The torso is equivalent in height and weight to an average adult male. It contains radiation detectors that will measure, in real-time, how much radiation the brain, thyroid, stomach, colon, and heart and lung area receive on a daily basis. The data will be used to determine how the body reacts to and shields its internal organs from radiation, which will be important for longer duration space flights.

Astronauts are exposed to approximately 50-2,000 millisieverts (mSv) while on six-month-duration missions to the International Space Station (ISS), the Moon and beyond. The risk of cancer caused by ionizing radiation is well documented at radiation doses beginning at 100mSv and above.

Related radiological effect studies have shown that survivors of the atomic bomb explosions in Hiroshima and Nagasaki, nuclear reactor workers and patients who have undergone therapeutic radiation treatments have received low-linear energy transfer (LET) radiation (x-rays and gamma rays) doses in the same 50-2,000 mSv range.

Composition of space radiation

While in space, astronauts are exposed to radiation which is mostly composed of high-energy protons, helium nuclei (alpha particles), and high-atomic-number ions (HZE ions), as well as secondary radiation from nuclear reactions from spacecraft parts or tissue.

The ionization patterns in molecules, cells, tissues and the resulting biological effects are distinct from typical terrestrial radiation (x-rays and gamma rays, which are low-LET radiation). Galactic cosmic rays (GCRs) from outside the Milky Way galaxy consist mostly of highly energetic protons with a small component of HZE ions.

Prominent HZE ions:

• Carbon (C)
• Oxygen (O)
• Magnesium (Mg)
• Silicon (Si)
• Iron (Fe)

GCR energy spectra peaks (with median energy peaks up to 1,000 MeV/amu) and nuclei (energies up to 10,000 MeV/amu) are important contributors to the dose equivalent.

Uncertainties in cancer projections

One of the main roadblocks to interplanetary travel is the risk of cancer caused by radiation exposure. The largest contributors to this roadblock are: (1) The large uncertainties associated with cancer risk estimates, (2) The unavailability of simple and effective countermeasures and (3) The inability to determine the effectiveness of countermeasures. Operational parameters that need to be optimized to help mitigate these risks include:

• length of space missions
• crew age
• crew sex
• shielding
• biological countermeasures

Major uncertainties

• effects on biological damage related to differences between space radiation and x-rays
• dependence of risk on dose-rates in space related to the biology of DNA repair, cell regulation and tissue responses
• predicting solar particle events (SPEs)
• extrapolation from experimental data to humans and between human populations
• individual radiation sensitivity factors (genetic, epigenetic, dietary or "healthy worker" effects)

Minor uncertainties

• data on galactic cosmic ray environments
• physics of shielding assessments related to transmission properties of radiation through materials and tissue
• microgravity effects on biological responses to radiation
• errors in human data (statistical, dosimetry or recording inaccuracies)

Quantitative methods have been developed to propagate uncertainties that contribute to cancer risk estimates. The contribution of microgravity effects on space radiation has not yet been estimated, but it is expected to be small. The effects of changes in oxygen levels or in immune dysfunction on cancer risks are largely unknown and are of great concern during space flight.

Types of cancer caused by radiation exposure

Studies are being conducted on populations accidentally exposed to radiation (such as Chernobyl, production sites, and Hiroshima and Nagasaki). These studies show strong evidence for cancer morbidity as well as mortality risks at more than 12 tissue sites. The largest risks for adults who have been studied include several types of leukemia, including myeloid leukemia and acute lymphatic lymphoma as well as tumors of the lung, breast, stomach, colon, bladder and liver. Inter-sex variations are very likely due to the differences in the natural incidence of cancer in males and females. Another variable is the additional risk for cancer of the breast, ovaries and lungs in females. There is also evidence of a declining risk of cancer caused by radiation with increasing age, but the magnitude of this reduction above the age of 30 is uncertain.

It is unknown whether high-LET radiation could cause the same types of tumors as low-LET radiation, but differences should be expected.

The ratio of a dose of high-LET radiation to a dose of x-rays or gamma rays that produce the same biological effect are called relative biological effectiveness (RBE) factors. The types of tumors in humans who are exposed to space radiation will be different from those who are exposed to low-LET radiation. This is evidenced by a study that observed mice with neutrons and have RBEs that vary with the tissue type and strain.

Measured rate of cancer among astronauts

The measured change rate of cancer is restricted by limited statistics. A study published in Scientific Reports looked over 301 U.S. astronauts and 117 Soviet and Russian cosmonauts, and found no measurable increase in cancer mortality compared to the general population, as reported by LiveScience.

An earlier 1998 study came to similar conclusions, with no statistically significant increase in cancer among astronauts compared to the reference group.

Approaches for setting acceptable risk levels

The various approaches to setting acceptable levels of radiation risk are summarized below:

Comparison of radiation doses - includes the amount detected on the trip from Earth to Mars by the RAD on the MSL (2011 - 2013).

• Unlimited Radiation Risk - NASA management, the families of loved ones of astronauts, and taxpayers would find this approach unacceptable.
• Comparison to Occupational Fatalities in Less-safe Industries - The life-loss from attributable radiation cancer death is less than that from most other occupational deaths. At this time, this comparison would also be very restrictive on ISS operations because of continued improvements in ground-based occupational safety over the last 20 years.
• Comparison to Cancer Rates in General Population - The number of years of life-loss from radiation-induced cancer deaths can be significantly larger than from cancer deaths in the general population, which often occur late in life (> age 70 years) and with significantly less numbers of years of life-loss.
• Doubling Dose for 20 Years Following Exposure - Provides a roughly equivalent comparison based on life-loss from other occupational risks or background cancer fatalities during a worker's career, however, this approach negates the role of mortality effects later in life.
• Use of Ground-based Worker Limits - Provides a reference point equivalent to the standard that is set on Earth, and recognizes that astronauts face other risks. However, ground workers remain well below dose limits, and are largely exposed to low-LET radiation where the uncertainties of biological effects are much smaller than for space radiation.

NCRP Report No. 153 provides a more recent review of cancer and other radiation risks. This report also identifies and describes the information needed to make radiation protection recommendations beyond LEO, contains a comprehensive summary of the current body of evidence for radiation-induced health risks and also makes recommendations on areas requiring future experimentation.

Current permissible exposure limits

Career cancer risk limits

Astronauts' radiation exposure limit is not to exceed 3% of the risk of exposure-induced death (REID) from fatal cancer over their career. It is NASA's policy to ensure a 95% confidence level (CL) that this limit is not exceeded. These limits are applicable to all missions in low Earth orbit (LEO) as well as lunar missions that are less than 180 days in duration. In the United States, the legal occupational exposure limits for adult workers is set at an effective dose of 50 mSv annually.

Cancer risk to dose relationship

The relationship between radiation exposure and risk is both age- and sex-specific due to latency effects and differences in tissue types, sensitivities, and life spans between sexes. These relationships are estimated using the methods that are recommended by the NCRP  and more recent radiation epidemiology information 

The principle of As Low As Reasonably Achievable

The as low as reasonably achievable (ALARA) principle is a legal requirement intended to ensure astronaut safety. An important function of ALARA is to ensure that astronauts do not approach radiation limits and that such limits are not considered as "tolerance values." ALARA is especially important for space missions in view of the large uncertainties in cancer and other risk projection models. Mission programs and terrestrial occupational procedures resulting in radiation exposures to astronauts are required to find cost-effective approaches to implement ALARA.

Evaluating career limits

Organ (T)	Tissue weighting factor (wT)
Gonads	0.20
Bone Marrow (red)	0.12
Colon	0.12
Lung	0.12
Stomach	0.12
Bladder	0.05
Breast	0.05
Liver	0.05
Esophagus	0.05
Thyroid	0.05
Skin	0.01
Bone Surface	0.01
Remainder*	0.05
*Adrenals, brain, upper intestine, small intestine, kidney, muscle, pancreas, spleen, thymus and uterus.

The risk of cancer is calculated by using radiation dosimetry and physics methods.

For the purpose of determining radiation exposure limits at NASA, the probability of fatal cancer is calculated as shown below:

1. The body is divided into a set of sensitive tissues, and each tissue, T, is assigned a weight, w_T, according to its estimated contribution to cancer risk.
2. The absorbed dose, D_γ, that is delivered to each tissue is determined from measured dosimetry. For the purpose of estimating radiation risk to an organ, the quantity characterizing the ionization density is the LET (keV/μm).
3. For a given interval of LET, between L and ΔL, the dose-equivalent risk (in units of sievert) to a tissue, T, H_γ(L) is calculated as
   ${\displaystyle H_{\gamma }(L)=Q(L)D_{\gamma }(L)}$
   where the quality factor, Q(L), is obtained according to the International Commission on Radiological Protection (ICRP).
4. The average risk to a tissue, T, due to all types of radiation contributing to the dose is given by
   ${\displaystyle H_{\gamma }=\int D_{\gamma }(L)Q(L)dL}$
   or, since ${\displaystyle D_{\gamma }(L)=LF_{\gamma }(L)}$, where F_γ(L) is the fluence of particles with LET=L, traversing the organ,
   ${\displaystyle H_{\gamma }=\int dLQ(L)F_{\gamma }(L)L}$
5. The effective dose is used as a summation over radiation type and tissue using the tissue weighting factors, w_γ
   ${\displaystyle E=\sum _{\gamma }w_{\gamma }H_{\gamma }}$
6. For a mission of duration t, the effective dose will be a function of time, E(t), and the effective dose for mission i will be
   ${\displaystyle E_{i}=\int E(t)dt}$
7. The effective dose is used to scale the mortality rate for radiation-induced death from the Japanese survivor data, applying the average of the multiplicative and additive transfer models for solid cancers and the additive transfer model for leukemia by applying life-table methodologies that are based on U.S. population data for background cancer and all causes of death mortality rates. A dose-dose rate effectiveness factor (DDREF) of 2 is assumed.

Evaluating cumulative radiation risks

The cumulative cancer fatality risk (%REID) to an astronaut for occupational radiation exposures, N, is found by applying life-table methodologies that can be approximated at small values of %REID by summing over the tissue-weighted effective dose, E_i, as

${\displaystyle Risk=\sum _{i=1}^{N}E_{i}R_{0}(age_{i},sex)}$

where R₀ are the age- and sex- specific radiation mortality rates per unit dose.

For organ dose calculations, NASA uses the model of Billings et al. to represent the self-shielding of the human body in a water-equivalent mass approximation. Consideration of the orientation of the human body relative to vehicle shielding should be made if it is known, especially for SPEs 

Confidence levels for career cancer risks are evaluated using methods that are specified by the NPRC in Report No. 126. These levels were modified to account for the uncertainty in quality factors and space dosimetry.

The uncertainties that were considered in evaluating the 95% confidence levels are the uncertainties in:

• Human epidemiology data, including uncertainties in
  • statistics limitations of epidemiology data
  • dosimetry of exposed cohorts
  • bias, including misclassification of cancer deaths, and
  • the transfer of risk across populations.
• The DDREF factor that is used to scale acute radiation exposure data to low-dose and dose-rate radiation exposures.
• The radiation quality factor (Q) as a function of LET.
• Space dosimetry

The so-called "unknown uncertainties" from the NCRP report No. 126 are ignored by NASA.

Models of cancer risks and uncertainties

Life-table methodology

The double-detriment life-table approach is what is recommended by the NPRC to measure radiation cancer mortality risks. The age-specific mortality of a population is followed over its entire life span with competing risks from radiation and all other causes of death described.

For a homogenous population receiving an effective dose E at age a_E, the probability of dying in the age-interval from a to a+1 is described by the background mortality-rate for all causes of death, M(a), and the radiation cancer mortality rate, m(E,a_E,a), as:

${\displaystyle q(E,a_{E},a)={\frac {M(a)+m(E,a_{E},a)}{1+{\frac {1}{2}}\left[M(a)+m(E,a_{E},a)\right]}}}$

The survival probability to age, a, following an exposure, E at age a_E, is:

${\displaystyle S(E,a_{E},a)=\prod _{u=a_{E}}^{a-1}\left[1-q(E,a_{E},u)\right]}$

The excessive lifetime risk (ELR - the increased probability that an exposed individual will die from cancer) is defined by the difference in the conditional survival probabilities for the exposed and the unexposed groups as:

${\displaystyle ELR=\sum _{a=a_{E}}^{\infty }\left[M(a)+m(E,a_{E},a)\right]S(E,a_{E},a)-\sum _{a=a_{E}}^{\infty }M(a)S(0,a_{E},a)}$

A minimum latency-time of 10 years is often used for low-LET radiation. Alternative assumptions should be considered for high-LET radiation. The REID (the lifetime risk that an individual in the population will die from cancer caused by radiation exposure) is defined by:

${\displaystyle REID=\sum _{a=a_{E}}^{\infty }m(E,a_{E},a)S(E,a_{E},a)}$

Generally, the value of the REID exceeds the value of the ELR by 10-20%.

The average loss of life-expectancy, LLE, in the population is defined by:

${\displaystyle LLE=\sum _{a=a_{E}}^{\infty }S(0,a_{E},a)-\sum _{a=a_{E}}^{\infty }S(E,a_{E},a)}$

The loss of life-expectancy among exposure-induced-deaths (LLE-REID) is defined by:

${\displaystyle LLE-REID={\frac {LLE}{REID}}}$

Uncertainties in low-LET epidemiology data

The low-LET mortality rate per sievert, m_i is written

${\displaystyle m(E,a_{x},a)={\frac {m_{0}(E,a_{x},a)}{DDREF}}{\frac {x_{D}x_{s}x_{T}x_{B}}{x_{Dr}}}}$

where m₀ is the baseline mortality rate per sievert and x_α are quantiles (random variables) whose values are sampled from associated probability distribution functions (PDFs), P(X_a).

NCRP, in Report No. 126, defines the following subjective PDFs, P(X_a), for each factor that contributes to the acute low-LET risk projection:

1. P_dosimetry is the random and systematic errors in the estimation of the doses received by atomic-bomb blast survivors.
2. P_statistical is the distribution in uncertainty in the point estimate of the risk coefficient, r₀.
3. P_bias is any bias resulting for over- or under-reporting cancer deaths.
4. P_transfer is the uncertainty in the transfer of cancer risk following radiation exposure from the Japanese population to the U.S. population.
5. P_Dr is the uncertainty in the knowledge of the extrapolation of risks to low dose and dose-rates, which are embodied in the DDREF.

Risk in context of exploration mission operational scenarios

The accuracy of galactic cosmic ray environmental models, transport codes and nuclear interaction cross sections allow NASA to predict space environments and organ exposure that may be encountered on long-duration space missions. The lack of knowledge of the biological effects of radiation exposure raise major questions about risk prediction.

The cancer risk projection for space missions is found by

${\displaystyle m_{J}(E,a_{E},a)_{lJ}(E,a_{E},a)\int dL{\frac {dF}{dL}}LQ_{trial-J}(L)X_{L-J}}$

where ${\displaystyle {\frac {dF}{dL}}}$ represents the folding of predictions of tissue-weighted LET spectra behind spacecraft shielding with the radiation mortality rate to form a rate for trial J.

Alternatively, particle-specific energy spectra, F_j(E), for each ion, j, can be used

${\displaystyle m_{J}(E,a_{E},a)=m_{lJ}(E,a_{E},a)\sum _{j}(E)L(E)Q_{trial-J}(L(E))x_{L-J}}$.

The result of either of these equations is inserted into the expression for the REID.

Related probability distribution functions (PDFs) are grouped together into a combined probability distribution function, P_cmb(x). These PDFs are related to the risk coefficient of the normal form (dosimetry, bias and statistical uncertainties). After a sufficient number of trials have been completed (approximately 10⁵), the results for the REID estimated are binned and the median values and confidence intervals are found.

The chi-squared (χ²) test is used for determining whether two separate PDFs are significantly different (denoted p₁(R_i) and p₂(R_i), respectively). Each p(R_i) follows a Poisson distribution with variance ${\displaystyle {\sqrt {p(R_{i})}}}$.

The χ² test for n-degrees of freedom characterizing the dispersion between the two distributions is

${\displaystyle \chi ^{2}=\sum _{n}{\frac {\left[p_{1}(R_{n})-p_{2}(R_{n})\right]^{2}}{\sqrt {p_{1}^{2}(R_{n})+p_{2}^{2}(R_{n})}}}}$.

The probability, P(ņχ²), that the two distributions are the same is calculated once χ² is determined.

Radiation carcinogenesis mortality rates

Age-and sex-dependent mortality rare per unit dose, multiplied by the radiation quality factor and reduced by the DDREF is used for projecting lifetime cancer fatality risks. Acute gamma ray exposures are estimated. The additivity of effects of each component in a radiation field is also assumed.

Rates are approximated using data gathered from Japanese atomic bomb survivors. There are two different models that are considered when transferring risk from Japanese to U.S. populations.

• Multiplicative transfer model - assumes that radiation risks are proportional to spontaneous or background cancer risks.
• Additive transfer model - assumes that radiation risk acts independently of other cancer risks.

The NCRP recommends a mixture model to be used that contains fractional contributions from both methods.

The radiation mortality rate is defined as:

${\displaystyle m(E,a_{E},a)=\left[ERR(a_{E},a)M_{c}(a)+(1-v)EAR(a_{E},a)\right]{\frac {\sum _{L}Q(L)F(L)L}{DDREF}}}$

Where:

• ERR = excess relative risk per sievert
• EAR = excess additive risk per sievert
• M_c(a) = the sex- and age-specific cancer mortality rate in the U.S. population
• F = the tissue-weighted fluence
• L = the LET
• v = the fractional division between the assumption of the multiplicative and additive risk transfer models. For solid cancer, it is assumed that v=1/2 and for leukemia, it is assumed that v=0.

Biological and physical countermeasures

Identifying effective countermeasures that reduce the risk of biological damage is still a long-term goal for space researchers. These countermeasures are probably not needed for extended duration lunar missions, but will be needed for other long-duration missions to Mars and beyond. On 31 May 2013, NASA scientists reported that a possible human mission to Mars may involve a great radiation risk based on the amount of energetic particle radiation detected by the RAD on the Mars Science Laboratory while traveling from the Earth to Mars in 2011-2012.

There are three fundamental ways to reduce exposure to ionizing radiation:

• increasing the distance from the radiation source
• reducing the exposure time
• shielding (i.e.: a physical barrier)

Shielding is a plausible option, but due to current launch mass restrictions, it is prohibitively costly. Also, the current uncertainties in risk projection prevent the actual benefit of shielding from being determined. Strategies such as drugs and dietary supplements to reduce the effects of radiation, as well as the selection of crew members are being evaluated as viable options for reducing exposure to radiation and effects of irradiation. Shielding is an effective protective measure for solar particle events. As far as shielding from GCR, high-energy radiation is very penetrating and the effectiveness of radiation shielding depends on the atomic make-up of the material used.

Antioxidants are effectively used to prevent the damage caused by radiation injury and oxygen poisoning (the formation of reactive oxygen species), but since antioxidants work by rescuing cells from a particular form of cell death (apoptosis), they may not protect against damaged cells that can initiate tumor growth.

Evidence sub-pages

The evidence and updates to projection models for cancer risk from low-LET radiation are reviewed periodically by several bodies, which include the following organizations:

• The NAS Committee on the Biological Effects of Ionizing Radiation
• The United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR)
• The ICRP
• The NCRP

These committees release new reports about every 10 years on cancer risks that are applicable to low-LET radiation exposures. Overall, the estimates of cancer risks among the different reports of these panels will agree within a factor of two or less. There is continued controversy for doses that are below 5 mSv, however, and for low dose-rate radiation because of debate over the linear no-threshold hypothesis that is often used in statistical analysis of these data. The BEIR VII report, which is the most recent of the major reports is used in the following sub-pages. Evidence for low-LET cancer effects must be augmented by information on protons, neutrons, and HZE nuclei that is only available in experimental models. Such data have been reviewed by NASA several times in the past and by the NCRP.

• Epidemiology data for low linear energy transfer radiation
• Radiobiology evidence for protons and HZE nuclei

Radiation-induced cancer

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Exposure to ionizing radiation is known to increase the future incidence of cancer, particularly leukemia. The mechanism by which this occurs is well understood, but quantitative models predicting the level of risk remain controversial. The most widely accepted model posits that the incidence of cancers due to ionizing radiation increases linearly with effective radiation dose at a rate of 5.5% per sievert; if correct, natural background radiation is the most hazardous source of radiation to general public health, followed by medical imaging as a close second. Additionally, the vast majority of non-invasive cancers are non-melanoma skin cancers caused by ultraviolet radiation (which lies on the boundary between ionizing and non-ionizing radiation). Non-ionizing radio frequency radiation from mobile phones, electric power transmission, and other similar sources have been described as a possible carcinogen by the WHO's International Agency for Research on Cancer, but the link remains unproven.

Causes

According to the prevalent model, any radiation exposure can increase the risk of cancer. Typical contributors to such risk include natural background radiation, medical procedures, occupational exposures, nuclear accidents, and many others. Some major contributors are discussed below.

Radon

Radon is responsible for the worldwide majority of the mean public exposure to ionizing radiation. It is often the single largest contributor to an individual's background radiation dose, and is the most variable from location to location. Radon gas from natural sources can accumulate in buildings, especially in confined areas such as attics, and basements. It can also be found in some spring waters and hot springs.

Epidemiological evidence shows a clear link between lung cancer and high concentrations of radon, with 21,000 radon-induced U.S. lung cancer deaths per year—second only to cigarette smoking—according to the United States Environmental Protection Agency. Thus in geographic areas where radon is present in heightened concentrations, radon is considered a significant indoor air contaminant.

Residential exposure to radon gas has similar cancer risks as passive smoking. Radiation is a more potent source of cancer when it is combined with other cancer-causing agents, such as radon gas exposure plus smoking tobacco.

Medical

In industrialized countries, Medical imaging contributes almost as much radiation dose to the public as natural background radiation. Collective dose to Americans from medical imaging grew by a factor of six from 1990 to 2006, mostly due to growing use of 3D scans that impart much more dose per procedure than traditional radiographs. CT scans alone, which account for half the medical imaging dose to the public, are estimated to be responsible for 0.4% of current cancers in the United States, and this may increase to as high as 1.5-2% with 2007 rates of CT usage; however, this estimate is disputed. Other nuclear medicine techniques involve the injection of radioactive pharmaceuticals directly into the bloodstream, and radiotherapy treatments deliberately deliver lethal doses (on a cellular level) to tumors and surrounding tissues.

It has been estimated that CT scans performed in the US in 2007 alone will result in 29,000 new cancer cases in future years. This estimate is criticized by the American College of Radiology (ACR), which maintains that the life expectancy of CT scanned patients is not that of the general population and that the model of calculating cancer is based on total-body radiation exposure and thus faulty.

Occupational

In accordance with ICRP recommendations, most regulators permit nuclear energy workers to receive up to 20 times more radiation dose than is permitted for the general public. Higher doses are usually permitted when responding to an emergency. The majority of workers are routinely kept well within regulatory limits, while a few essential technicians will routinely approach their maximum each year. Accidental overexposures beyond regulatory limits happen globally several times a year. Astronauts on long missions are at higher risk of cancer, see cancer and spaceflight.

Some occupations are exposed to radiation without being classed as nuclear energy workers. Airline crews receive occupational exposures from cosmic radiation because of reduced atmospheric shielding at altitude. Mine workers receive occupational exposures to radon, especially in uranium mines. Anyone working in a granite building, such as the US Capitol, is likely to receive a dose from natural uranium in the granite.

Accidental

Chernobyl radiation map from 1996

Nuclear accidents can have dramatic consequences to their surroundings, but their global impact on cancer is less than that of natural and medical exposures.

The most severe nuclear accident is probably the Chernobyl disaster. In addition to conventional fatalities and acute radiation syndrome fatalities, nine children died of thyroid cancer, and it is estimated that there may be up to 4,000 excess cancer deaths among the approximately 600,000 most highly exposed people. Of the 100 million curies (4 exabecquerels) of radioactive material, the short lived radioactive isotopes such as ¹³¹I Chernobyl released were initially the most dangerous. Due to their short half-lives of 5 and 8 days they have now decayed, leaving the more long-lived ¹³⁷Cs (with a half-life of 30.07 years) and ⁹⁰Sr (with a half-life of 28.78 years) as main dangers.

In March 2011, an earthquake and tsunami caused damage that led to explosions and partial meltdowns at the Fukushima I Nuclear Power Plant in Japan. Significant release of radioactive material took place following hydrogen explosions at three reactors, as technicians tried to pump in seawater to keep the uranium fuel rods cool, and bled radioactive gas from the reactors in order to make room for the seawater. Concerns about the large-scale release of radioactivity resulted in 20 km exclusion zone being set up around the power plant and people within the 20–30 km zone being advised to stay indoors. On March 24, 2011, Japanese officials announced that "radioactive iodine-131 exceeding safety limits for infants had been detected at 18 water-purification plants in Tokyo and five other prefectures".

In 2003, in autopsies performed on 6 children dead in the polluted area near Chernobyl where they also reported a higher incidence of pancreatic tumors, Bandazhevsky found a concentration of 137-Cs of 40-45 times higher than in their liver, thus demonstrating that pancreatic tissue is a strong accumulator of radioactive cesium. In 2020, Zrielykh reported a high and statistically significant incidence of pancreatic cancer in Ukraine for a period of 10 year, there have been cases of morbidity also in children in 2013 compared with 2003.

Other serious radiation accidents include the Kyshtym disaster (estimated 49 to 55 cancer deaths), and the Windscale fire (an estimated 33 cancer deaths).

The Transit 5BN-3 SNAP 9A accident. On April 21, 1964, the satellite containing plutonium burnt up in the atmosphere. Dr. John Gofman claimed it increased the rate of lung cancer worldwide. He said "Although it is impossible to estimate the number of lung cancers induced by the accident, there is no question that the dispersal of so much Plutonium-238 would add to the number of lung cancer diagnosed over many subsequent decades."

Mechanism

Cancer is a stochastic effect of radiation, meaning it is an unpredictable event. The probability of occurrence increases with effective radiation dose, but the severity of the cancer is independent of dose. The speed at which cancer advances, the prognosis, the degree of pain, and every other feature of the disease are not functions of the radiation dose to which the person is exposed. This contrasts with the deterministic effects of acute radiation syndrome which increase in severity with dose above a threshold. Cancer starts with a single cell whose operation is disrupted. Normal cell operation is controlled by the chemical structure of DNA molecules, also called chromosomes.

When radiation deposits enough energy in organic tissue to cause ionization, this tends to break molecular bonds, and thus alter the molecular structure of the irradiated molecules. Less energetic radiation, such as visible light, only causes excitation, not ionization, which is usually dissipated as heat with relatively little chemical damage. Ultraviolet light is usually categorized as non-ionizing, but it is actually in an intermediate range that produces some ionization and chemical damage. Hence the carcinogenic mechanism of ultraviolet radiation is similar to that of ionizing radiation.

Unlike chemical or physical triggers for cancer, penetrating radiation hits molecules within cells randomly. Molecules broken by radiation can become highly reactive free radicals that cause further chemical damage. Some of this direct and indirect damage will eventually impact chromosomes and epigenetic factors that control the expression of genes. Cellular mechanisms will repair some of this damage, but some repairs will be incorrect and some chromosome abnormalities will turn out to be irreversible.

DNA double-strand breaks (DSBs) are generally accepted to be the most biologically significant lesion by which ionizing radiation causes cancer. In vitro experiments show that ionizing radiation cause DSBs at a rate of 35 DSBs per cell per Gray, and removes a portion of the epigenetic markers of the DNA, which regulate the gene expression. Most of the induced DSBs are repaired within 24h after exposure, however, 25% of the repaired strands are repaired incorrectly and about 20% of fibroblast cells that were exposed to 200mGy died within 4 days after exposure. A portion of the population possess a flawed DNA repair mechanism, and thus suffer a greater insult due to exposure to radiation.

Major damage normally results in the cell dying or being unable to reproduce. This effect is responsible for acute radiation syndrome, but these heavily damaged cells cannot become cancerous. Lighter damage may leave a stable, partly functional cell that may be capable of proliferating and eventually developing into cancer, especially if tumor suppressor genes are damaged. The latest research suggests that mutagenic events do not occur immediately after irradiation. Instead, surviving cells appear to have acquired a genomic instability which causes an increased rate of mutations in future generations. The cell will then progress through multiple stages of neoplastic transformation that may culminate into a tumor after years of incubation. The neoplastic transformation can be divided into three major independent stages: morphological changes to the cell, acquisition of cellular immortality (losing normal, life-limiting cell regulatory processes), and adaptations that favor formation of a tumor.

In some cases, a small radiation dose reduces the impact of a subsequent, larger radiation dose. This has been termed an 'adaptive response' and is related to hypothetical mechanisms of hormesis.

A latent period of decades may elapse between radiation exposure and the detection of cancer. Those cancers that may develop as a result of radiation exposure are indistinguishable from those that occur naturally or as a result of exposure to other carcinogens. Furthermore, National Cancer Institute literature indicates that chemical and physical hazards and lifestyle factors, such as smoking, alcohol consumption, and diet, significantly contribute to many of these same diseases. Evidence from uranium miners suggests that smoking may have a multiplicative, rather than additive, interaction with radiation. Evaluations of radiation's contribution to cancer incidence can only be done through large epidemiological studies with thorough data about all other confounding risk factors.

Skin cancer

Prolonged exposure to ultraviolet radiation from the sun can lead to melanoma and other skin malignancies. Clear evidence establishes ultraviolet radiation, especially the non-ionizing medium wave UVB, as the cause of most non-melanoma skin cancers, which are the most common forms of cancer in the world.

Skin cancer may occur following ionizing radiation exposure following a latent period averaging 20 to 40 years. A Chronic radiation keratosis is a precancerous keratotic skin lesion that may arise on the skin many years after exposure to ionizing radiation. Various malignancies may develop, most frequency basal-cell carcinoma followed by squamous-cell carcinoma. Elevated risk is confined to the site of radiation exposure. Several studies have also suggested the possibility of a causal relationship between melanoma and ionizing radiation exposure. The degree of carcinogenic risk arising from low levels of exposure is more contentious, but the available evidence points to an increased risk that is approximately proportional to the dose received. Radiologists and radiographers are among the earliest occupational groups exposed to radiation. It was the observation of the earliest radiologists that led to the recognition of radiation-induced skin cancer—the first solid cancer linked to radiation—in 1902. While the incidence of skin cancer secondary to medical ionizing radiation was higher in the past, there is also some evidence that risks of certain cancers, notably skin cancer, may be increased among more recent medical radiation workers, and this may be related to specific or changing radiologic practices. Available evidence indicates that the excess risk of skin cancer lasts for 45 years or more following irradiation.

Epidemiology

Cancer is a stochastic effect of radiation, meaning that it only has a probability of occurrence, as opposed to deterministic effects which always happen over a certain dose threshold. The consensus of the nuclear industry, nuclear regulators, and governments, is that the incidence of cancers due to ionizing radiation can be modeled as increasing linearly with effective radiation dose at a rate of 5.5% per sievert. Individual studies, alternate models, and earlier versions of the industry consensus have produced other risk estimates scattered around this consensus model. There is general agreement that the risk is much higher for infants and fetuses than adults, higher for the middle-aged than for seniors, and higher for women than for men, though there is no quantitative consensus about this. This model is widely accepted for external radiation, but its application to internal contamination is disputed. For example, the model fails to account for the low rates of cancer in early workers at Los Alamos National Laboratory who were exposed to plutonium dust, and the high rates of thyroid cancer in children following the Chernobyl accident, both of which were internal exposure events. Chris Busby of the self styled "European Committee on Radiation Risk", calls the ICRP model "fatally flawed" when it comes to internal exposure.

Radiation can cause cancer in most parts of the body, in all animals, and at any age, although radiation-induced solid tumors usually take 10–15 years, and can take up to 40 years, to become clinically manifest, and radiation-induced leukemias typically require 2–9 years to appear. Some people, such as those with nevoid basal cell carcinoma syndrome or retinoblastoma, are more susceptible than average to developing cancer from radiation exposure. Children and adolescents are twice as likely to develop radiation-induced leukemia as adults; radiation exposure before birth has ten times the effect.

Radiation exposure can cause cancer in any living tissue, but high-dose whole-body external exposure is most closely associated with leukemia, reflecting the high radiosensitivity of bone marrow. Internal exposures tend to cause cancer in the organs where the radioactive material concentrates, so that radon predominantly causes lung cancer, iodine-131 for thyroid cancer is most likely to cause leukemia.

Data sources

Increased Risk of Solid Cancer with Dose for atomic blast survivors

The associations between ionizing radiation exposure and the development of cancer are based primarily on the "LSS cohort" of Japanese atomic bomb survivors, the largest human population ever exposed to high levels of ionizing radiation. However this cohort was also exposed to high heat, both from the initial nuclear flash of infrared light and following the blast due their exposure to the firestorm and general fires that developed in both cities respectively, so the survivors also underwent Hyperthermia therapy to various degrees. Hyperthermia, or heat exposure following irradiation is well known in the field of radiation therapy to markedly increase the severity of free-radical insults to cells following irradiation. Presently however no attempts have been made to cater for this confounding factor, it is not included or corrected for in the dose-response curves for this group.

Additional data has been collected from recipients of selected medical procedures and the 1986 Chernobyl disaster. There is a clear link (see the UNSCEAR 2000 Report, Volume 2: Effects) between the Chernobyl accident and the unusually large number, approximately 1,800, of thyroid cancers reported in contaminated areas, mostly in children.

For low levels of radiation, the biological effects are so small they may not be detected in epidemiological studies. Although radiation may cause cancer at high doses and high dose rates, public health data regarding lower levels of exposure, below about 10 mSv (1,000 mrem), are harder to interpret. To assess the health impacts of lower radiation doses, researchers rely on models of the process by which radiation causes cancer; several models that predict differing levels of risk have emerged.

Studies of occupational workers exposed to chronic low levels of radiation, above normal background, have provided mixed evidence regarding cancer and transgenerational effects. Cancer results, although uncertain, are consistent with estimates of risk based on atomic bomb survivors and suggest that these workers do face a small increase in the probability of developing leukemia and other cancers. One of the most recent and extensive studies of workers was published by Cardis, et al. in 2005 . There is evidence that low level, brief radiation exposures are not harmful.

Modelling

Alternative assumptions for the extrapolation of the cancer risk vs. radiation dose to low-dose levels, given a known risk at a high dose: supra-linearity (A), linear (B), linear-quadratic (C) and hormesis (D).

The linear dose-response model suggests that any increase in dose, no matter how small, results in an incremental increase in risk. The linear no-threshold model (LNT) hypothesis is accepted by the International Commission on Radiological Protection (ICRP) and regulators around the world. According to this model, about 1% of the global population develop cancer as a result of natural background radiation at some point in their lifetime. For comparison, 13% of deaths in 2008 are attributed to cancer, so background radiation could plausibly be a small contributor.

Many parties have criticized the ICRP's adoption of the linear no-threshold model for exaggerating the effects of low radiation doses. The most frequently cited alternatives are the “linear quadratic” model and the “hormesis” model. The linear quadratic model is widely viewed in radiotherapy as the best model of cellular survival, and it is the best fit to leukemia data from the LSS cohort.

Linear no-threshold	F(D)=α⋅D
Linear quadratic	F(D)=α⋅D+β⋅D2
Hormesis	F(D)=α⋅[D−β]

In all three cases, the values of alpha and beta must be determined by regression from human exposure data. Laboratory experiments on animals and tissue samples is of limited value. Most of the high quality human data available is from high dose individuals, above 0.1 Sv, so any use of the models at low doses is an extrapolation that might be under-conservative or over-conservative. There is not enough human data available to settle decisively which of these model might be most accurate at low doses. The consensus has been to assume linear no-threshold because it the simplest and most conservative of the three.

Radiation hormesis is the conjecture that a low level of ionizing radiation (i.e., near the level of Earth's natural background radiation) helps "immunize" cells against DNA damage from other causes (such as free radicals or larger doses of ionizing radiation), and decreases the risk of cancer. The theory proposes that such low levels activate the body's DNA repair mechanisms, causing higher levels of cellular DNA-repair proteins to be present in the body, improving the body's ability to repair DNA damage. This assertion is very difficult to prove in humans (using, for example, statistical cancer studies) because the effects of very low ionizing radiation levels are too small to be statistically measured amid the "noise" of normal cancer rates.

The idea of radiation hormesis is considered unproven by regulatory bodies. If the hormesis model turns out to be accurate, it is conceivable that current regulations based on the LNT model will prevent or limit the hormetic effect, and thus have a negative impact on health.

Other non-linear effects have been observed, particularly for internal doses. For example, iodine-131 is notable in that high doses of the isotope are sometimes less dangerous than low doses, since they tend to kill thyroid tissues that would otherwise become cancerous as a result of the radiation. Most studies of very-high-dose I-131 for treatment of Graves disease have failed to find any increase in thyroid cancer, even though there is linear increase in thyroid cancer risk with I-131 absorption at moderate doses.

Public safety

Low-dose exposures, such as living near a nuclear power plant or a coal-fired power plant, which has higher emissions than nuclear plants, are generally believed to have no or very little effect on cancer development, barring accidents. Greater concerns include radon in buildings and overuse of medical imaging.

The International Commission on Radiological Protection (ICRP) recommends limiting artificial irradiation of the public to an average of 1 mSv (0.001 Sv) of effective dose per year, not including medical and occupational exposures. For comparison, radiation levels inside the US capitol building are 0.85 mSv/yr, close to the regulatory limit, because of the uranium content of the granite structure. According to the ICRP model, someone who spent 20 years inside the capitol building would have an extra one in a thousand chance of getting cancer, over and above any other existing risk. (20 yr X 0.85 mSv/yr X 0.001 Sv/mSv X 5.5%/Sv = ~0.1%) That "existing risk" is much higher; an average American would have a one in ten chance of getting cancer during this same 20-year period, even without any exposure to artificial radiation.

Internal contamination due to ingestion, inhalation, injection, or absorption is a particular concern because the radioactive material may stay in the body for an extended period of time, "committing" the subject to accumulating dose long after the initial exposure has ceased, albeit at low dose rates. Over a hundred people, including Eben Byers and the radium girls, have received committed doses in excess of 10 Gy and went on to die of cancer or natural causes, whereas the same amount of acute external dose would invariably cause an earlier death by acute radiation syndrome.

Internal exposure of the public is controlled by regulatory limits on the radioactive content of food and water. These limits are typically expressed in becquerel/kilogram, with different limits set for each contaminant.

History

Although radiation was discovered in late 19th century, the dangers of radioactivity and of radiation were not immediately recognized. Acute effects of radiation were first observed in the use of X-rays when Wilhelm Röntgen intentionally subjected his fingers to X-rays in 1895. He published his observations concerning the burns that developed, though he attributed them to ozone rather than to X-rays. His injuries healed later.

The genetic effects of radiation, including the effects on cancer risk, were recognized much later. In 1927 Hermann Joseph Muller published research showing genetic effects, and in 1946 was awarded the Nobel prize for his findings. Radiation was soon linked to bone cancer in the radium dial painters, but this was not confirmed until large-scale animal studies after World War II. The risk was then quantified through long-term studies of atomic bomb survivors.

Before the biological effects of radiation were known, many physicians and corporations had begun marketing radioactive substances as patent medicine and radioactive quackery. Examples were radium enema treatments, and radium-containing waters to be drunk as tonics. Marie Curie spoke out against this sort of treatment, warning that the effects of radiation on the human body were not well understood. Curie later died of aplastic anemia, not cancer. Eben Byers, a famous American socialite, died of multiple cancers in 1932 after consuming large quantities of radium over several years; his death drew public attention to dangers of radiation. By the 1930s, after a number of cases of bone necrosis and death in enthusiasts, radium-containing medical products had nearly vanished from the market.

In the United States, the experience of the so-called Radium Girls, where thousands of radium-dial painters contracted oral cancers, popularized the warnings of occupational health associated with radiation hazards. Robley D. Evans, at MIT, developed the first standard for permissible body burden of radium, a key step in the establishment of nuclear medicine as a field of study. With the development of nuclear reactors and nuclear weapons in the 1940s, heightened scientific attention was given to the study of all manner of radiation effects.