Spaceflight radiation carcinogenesis

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:
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:
Minor uncertainties.
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:
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.
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.
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:
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, "Ei", as
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:
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 aE, 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,aE,a)", as:
The survival probability to age, "a", following an exposure, "E" at age "aE", is:
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:
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:
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:
The loss of life-expectancy among exposure-induced-deaths (LLE-REID) is defined by:
Uncertainties in low-LET epidemiology data.
The low-LET mortality rate per sievert, "mi" is written
where "m0" is the baseline mortality rate per sievert and "xα" are quantiles (random variables) whose values are sampled from associated probability distribution functions (PDFs), "P(Xa)".
NCRP, in Report No. 126, defines the following subjective PDFs, "P(Xa)", for each factor that contributes to the acute low-LET risk projection:
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 
where formula_16 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, "Fj(E)", for each ion, "j", can be used 
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, "Pcmb(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(Ri)" and "p2(Ri)", respectively). Each "p(Ri)" follows a Poisson distribution with variance formula_18.
The χ2 test for n-degrees of freedom characterizing the dispersion between the two distributions is 
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.
The NCRP recommends a mixture model to be used that contains fractional contributions from both methods.
The radiation mortality rate is defined as:
Where:
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:
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:
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.