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{{multiple issues|
{{cleanup|reason = This article reads as if it is a research paper and not an encyclopedia article (in part because it is mostly cut and paste from the public domain study by NASA). It needs to be moved to a more encyclopedic topic heading, perhaps something like [[Cancer and spaceflight]], and re-written in an encyclopedia article style.|date=July 2012}}
{{expert-subject|Medicine|ex2=Spaceflight|date=July 2012}}
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[[File:iss002e5952.jpg|thumb|300px|The Phantom Torso, 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 mSv ([[Sievert|mili-Sievert]]) while on six-month-duration missions<!-- need to clarify, missions of the same duration in LEO would expect to receive much less radiation than same-duration missions to the moon which pass through the radiation belts --> to the [[International Space Station]] (ISS), the moon and beyond.<ref name="Cucinotta and Durante 2006">{{cite journal|last=Cucinotta|first=FA|coauthors=Durante, M|title=Cancer risk from exposure to galactic cosmic rays: implications for space exploration by human beings|journal=Lancet Oncol.|year=2006|volume=7|pages=431–435|doi=10.1016/S1470-2045(06)70695-7|issue=5|pmid=16648048}}</ref><ref name="Cucinotta 2008">{{cite journal|last=Cucinotta|first=FA|coauthors=Kim, MH; Willingham, V; George, KA|title=Physical and biological organ dosimetry analysis for international space station astronauts|journal=Radiation research|date=Jul 2008|volume=170|issue=1|pages=127–38|pmid=18582161|doi=10.1667/RR1330.1}}</ref>  The risk of cancer caused by [[ionizing radiation]] is well documented at radiation doses beginning at 50 mSv and above.<ref name="Cucinotta and Durante 2006" /><ref name="Durante 2008">{{cite journal|last=Durante|first=M|coauthors=Cucinotta, FA|title=Heavy ion carcinogenesis and human space exploration|journal=Nature reviews. Cancer|date=June 2008|volume=8|issue=6|pages=465–72|pmid=18451812|url=http://nix.nasa.gov/search.jsp?R=20080012531&qs=N%3D4294595076%2B4294290746|doi=10.1038/nrc2391}}</ref><ref name="BIER 2006">{{cite book|last=BIER|first=Committee to assess Health Risks from Exposure to Low levels of Ionizing Radiation|title=Health risks from exposure to low levels of ionizing radiation: BIER VII - Phase 2|year=2006|publisher=The National Academies Press|location=Washington, D.C.|url=http://www.nap.edu/openbook.php?isbn=030909156X|coauthors=National Research Council of the National Academies}}</ref>

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 [[Radiation therapy|therapeutic radiation treatments]] have received [http://medical-dictionary.thefreedictionary.com/linear+energy+transfer low-linear energy transfer (LET)] radiation ([[x-rays]] and [[gamma rays]]) doses in the same 50-2000 mSv range.<ref>{{cite web|last=Cucinotta|first=F.A.|title=Risk of Radiation Carcinogenesis|url=http://humanresearchroadmap.nasa.gov/evidence/reports/Carcinogenesis.pdf|work=Human Health and Performance Risks of Space Exploration Missions Evidence reviewed by the NASA Human Research Program|publisher=NASA|accessdate=6 June 2012|coauthors=Durante, M.|page=121}}</ref>

==Composition of space radiation==
While in space, astronauts are exposed to [[protons]], [[helium]] nuclei, and high-Z high energy ions ([[HZE ions]]), as well as [[secondary radiation]] from nuclear reactions from spacecraft parts or tissue.<ref name=122-123 />

Space radiation is composed mostly of high-energy protons, helium nuclei, and HZE ions.  The ionization patterns in molecules, cells, tissues and the resulting biological insults are distinct from typical terrestrial radiation ([[x-ray]]s and [[gamma ray]]s, which are [http://medical-dictionary.thefreedictionary.com/linear+energy+transfer low-LET radiation]).  [[Galactic cosmic ray|GCRs (galactic cosmic rays)]] from outside of the [[Milky Way|Milky Way galaxy]] consist mostly of highly energetic protons with a small component of HZE ions.<ref name=122-123 />

Prominent HZE ions:
* [[Carbon|carbon (C)]]
* [[Oxygen|oxygen (O)]]
* [[Magnesium|magnesium (Mg)]]
* [[Silicon|silicon (Si)]]
* [[Iron|iron (Fe)]]
[[Galactic cosmic ray|GCR (galactic cosmic ray)]]<ref>{{cite web|title=Galactic Cosmic Rays|url=http://helios.gsfc.nasa.gov/gcr.html|publisher=NASA|accessdate=6 June 2012}}</ref> energy spectra peaks (with median energy peaks up to 1,000 [[Electronvolt|MeV]]/amu) and nuclei (energies up to 10,000 [[Electronvolt|MeV]]/amu) are important contributors to the dose equivalent.<ref name=122-123 />

==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. <br><ref name="122-123">{{cite web|last=Cucinotta|first=F.A.|title=Risk of Radiation Carcinogenesis|url=http://humanresearchroadmap.nasa.gov/evidence/reports/Carcinogenesis.pdf|work=Human Health and Performance Risks of Space Exploration Missions Evidence reviewed by the NASA Human Research Program|publisher=NASA|accessdate=6 June 2012|coauthors=Durante, M.|pages=122–123}}</ref> 
Operational parameters that need to be optimized to help mitigate these risks include:<ref name=122-123 /> 
* length of space missions
* crew age
* crew gender
* shielding
* biological countermeasures

===Major uncertainties<ref name=122-123 />===
* 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<ref name=122-123 />===
* data on [[Galactic cosmic ray|GCR (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.<ref name=122-123 />

==Types of cancer caused by radiation exposure==
Studies are being conducted on populations accidentally exposed to radiation ([[Chernobyl]], production sites as well as [[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]] <ref name=126-126 /> and acute lymphatic lymphoma <ref name=126-126 /> as well as tumors of the [[Lung cancer|lung]], [[Breast cancer|breast]], [[Stomach cancer|stomach]], [[Colorectal cancer|colon]], [[Bladder cancer|bladder]] and [[Liver cancer|liver]].  Inter-gender 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.<ref name="NCRP 2000">{{cite book|last=NCRP|title=NCRP Report No. 132, Radiation Protection Guidance for Activities in Low-Earth Orbit|year=2000|publisher=NCRP|location=Bethseda, Md.|url=http://www.ncrponline.org/Publications/Press_Releases/132press.html}}</ref>  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.<ref name=122-123 />

It is unknown whether high-LET radiation could cause the same types of tumors as low-LET radiation, but differences should be expected.<ref name=126-126>{{cite web|last=Cucinotta|first=F.A.|title=Risk of Radiation Carcinogenesis|url=http://humanresearchroadmap.nasa.gov/evidence/reports/Carcinogenesis.pdf|work=Human Health and Performance Risks of Space Exploration Missions Evidence reviewed by the NASA Human Research Program|publisher=NASA|accessdate=8 June 2012|coauthors=Durante, M.|pages=126–126}}</ref>

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 (BRE) 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.<ref name=126-126 />

==Approaches for Setting Acceptable Risk Levels==
The various approaches to setting acceptable levels of radiation risk are summarized below:<ref name=137-138>{{cite web|last=Cucinotta|first=F.A.|title=Risk of Radiation Carcinogenesis|url=http://humanresearchroadmap.nasa.gov/evidence/reports/Carcinogenesis.pdf|work=Human Health and Performance Risks of Space Exploration Missions Evidence reviewed by the NASA Human Research Program|publisher=NASA|accessdate=8 June 2012|coauthors=Durante, M.|pages=137–138}}</ref>
[[File:PIA17601-Comparisons-RadiationExposure-MarsTrip-20131209.png|thumb|250px|right|Comparison of Radiation Doses - includes the amount detected on the trip from Earth to Mars by the [[Radiation assessment detector|RAD]] on the [[Mars Science Laboratory|MSL]] (2011 - 2013).<ref name="SCI-20130531a">{{cite journal |last=Kerr |first=Richard |title=Radiation Will Make Astronauts' Trip to Mars Even Riskier |url=http://www.sciencemag.org/content/340/6136/1031.summary |date=31 May 2013 |journal=[[Science (journal)|Science]] |volume=340 |page=1031 |doi=10.1126/science.340.6136.1031 |accessdate=31 May 2013 |issue=6136 }}</ref><ref name="SCI-20130531b">{{cite journal |title=Measurements of Energetic Particle Radiation in Transit to Mars on the Mars Science Laboratory |url=http://www.sciencemag.org/content/340/6136/1080.abstract |journal=[[Science (journal)|Science]] |date=31 May 2013 |volume=340 |pages=1080–1084 |doi=10.1126/science.1235989 |accessdate=31 May 2013 |author=Zeitlin, C. et al. |issue=6136 |last2=Hassler |first2=D. M. |last3=Cucinotta |first3=F. A. |last4=Ehresmann |first4=B. |last5=Wimmer-Schweingruber |first5=R. F. |last6=Brinza |first6=D. E. |last7=Kang |first7=S. |last8=Weigle |first8=G. |last9=Bottcher |first9=S. }}</ref><ref name="NYT-20130530">{{cite news |last=Chang |first=Kenneth |title=Data Point to Radiation Risk for Travelers to Mars |url=http://www.nytimes.com/2013/05/31/science/space/data-show-higher-cancer-risk-for-mars-astronauts.html |date=30 May 2013 |publisher=[[New York Times]] |accessdate=31 May 2013 }}</ref><ref name="SN-20130629">{{cite journal |last=Gelling |first=Cristy|title=Mars trip would deliver big radiation dose; Curiosity instrument confirms expectation of major exposures|url=http://www.sciencenews.org/view/generic/id/350728/description/Mars_trip_would_deliver_big_radiation_dose|volume=183 |issue=13 |page=8 |journal=[[Science News]] |date=June 29, 2013 |accessdate=July 8, 2013 }}</ref> ]]
* 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.

[http://www.ncrponline.org/Publications/Press_Releases/153press.html NCRP Report No. 153 (NCRP, 2006)] 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.<ref name=137-138 />

==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|low Earth orbit (LEO)]] as well as lunar missions that are less than 180 days in duration.<ref name="127-131">{{cite web|last=Cucinotta|first=F.A.|title=Risk of Radiation Carcinogenesis|url=http://humanresearchroadmap.nasa.gov/evidence/reports/Carcinogenesis.pdf|work=Human Health and Performance Risks of Space Exploration Missions Evidence reviewed by the NASA Human Research Program|publisher=NASA|accessdate=12 June 2012|coauthors=Durante, M.|pages=127–131}}</ref>

===Cancer Risk to Dose Relationship===
The relationship between radiation exposure and risk is both age- and gender-specific due to latency effects and differences in tissue types, sensitivities, and life spans between genders.  These relationships are estimated using the methods that are recommended by the NCRP <ref name="NCRP 2000" /> and more recent radiation epidemiology inormation <ref name="Cucinotta and Durante 2006" /><ref name=127-131 /><ref name="Preston 2003">{{cite journal|last=Preston|first=DL|coauthors=Shimizu, Y; Pierce, DA; Suyama, A; Mabuchi, K|title=Studies of mortality of atomic bomb survivors. Report 13: Solid cancer and noncancer disease mortality: 1950-1997|journal=Radiation research|date=Oct 2003|volume=160|issue=4|pages=381–407|pmid=12968934|url=http://cerrie.org/committee_papers/Paper_12-04b.pdf|doi=10.1667/RR3049}}</ref>

===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.<ref name=127-131 />

==Evaluating Career Limits==

{| class="wikitable" <div style="text-align: center;"> style="float:right;"
!Organ (''T'')
!Tissue weighting factor (''w<sub>T</sub>'')
|-
|Gonads
| align="center" | 0.20
|-
|Bone Marrow (red)
| align="center" | 0.12
|-
|Colon
| align="center" | 0.12
|-
|Lung
| align="center" | 0.12
|-
|Stomach
| align="center" | 0.12
|-
|Bladder
| align="center" | 0.05
|-
|Breast
| align="center" | 0.05
|-
|Liver
| align="center" | 0.05
|-
|Esophagus
| align="center" | 0.05
|-
|Thyroid
| align="center" | 0.05
|-
|Skin
| align="center" | 0.01
|-
|Bone Surface
| align="center" | 0.01
|-
|Remainder*
| align="center" | 0.05
|-
|<sub>*Adrenals, brain, upper intestine,<br> small intestine, kidney, muscle,<br> pancreas, spleen, thymus and uterus.</sub>
|}</div>

The risk of cancer is calculated by using [[Dosimetry|radiation dosimetry]] and physics methods.<ref name=127-131 />

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

# The body is divided into a set of sensitive tissues, and each tissue, ''T'', is assigned a weight, ''w<sub>T</sub>'', according to its estimated contribution to cancer risk.<ref name=127-131 />
# The absorbed dose, ''D<sub>γ</sub>'', 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).<ref name=127-131 />
# For a given interval of LET, between L and ΔL, the dose-equivalent risk (in units of Sievert, where 1 SV = 100 rem) to a tissue, ''T'', ''H<sub>γ</sub>(L)'' is calculated as<br><math>H_\gamma (L) = Q(L)D_\gamma (L)</math><br>where the quality factor, Q(L), is obtained according to the [http://www.icrp.org International Commission on Radiological Protection (ICRP)].<ref name=127-131 />
# The average risk to a tissue, ''T'', due to all types of radiation contributing to the dose is given by <ref name=127-131 /><br><math>H_\gamma = \int D_\gamma (L)Q(L)dL</math><br>or, since <math>D_\gamma (L) =  LF_\gamma (L)</math>, where ''F<sub>γ</sub>(L)'' is the fluence of particles with ''LET=L'', traversing the organ,<br><math>H_\gamma = \int dLQ(L)F_\gamma (L)L</math>
# The effective dose is used as a summation over radiation type and tissue using the tissue weighting factors, ''w<sub>γ</sub>'' <ref name=127-131 /><br><math>E=\sum_\gamma w_\gamma H_\gamma</math>
# 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  <ref name=127-131 /><br><math>E_i = \int E(t) dt</math>
# 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.<ref name=127-131 />

===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<sub>i</sub>'', as<br>
::<math>Risk = \sum_{i=1}^N E_i R_0 (age_i, gender)</math>
where ''R<sub>0</sub>'' are the age- and gender- specific radiation mortality rates per unit dose.<ref name=127-131 />

For organ dose calculations, NASA uses the model of Billings et al.<ref name=Billings>{{cite book|last=Billings|first=MP|title=Body self-shielding data analysis|year=1973|publisher=McDonnell-Douglas Astronautics Company West|edition=MDC-G4131|coauthors=Yucker, WR; Heckman, BR}}</ref> 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 <ref name=Wilson>{{cite journal|last=Wilson|first=JW|coauthors=Kim, M; Schimmerling, W; Badavi, FF; Thibeaullt, SA; Cucinotta, FA; Shinn, JL; Kiefer, R|title=Issues in space radiation protection|journal=Health Phys,|year=1993|volume=68|pages=50–58|url=http://ntrs.nasa.gov/archive/nasa/casi.ntrs.nasa.gov/19970006977_1997005102.pdf|doi=10.1097/00004032-199501000-00006}}</ref>

Confidence levels for career cancer risks are evaluated using methods that are specified by the [http://www.ncrponline.org/Publications/Press_Releases/126press.html NPRC in Report No. 126].<ref name=127-131 />  These levels were modified to account for the uncertainty in quality factors and space dosimetry.<ref name="Cucinotta and Durante 2006" /><ref name=127-131 /><ref name="Cucinotta 2001">{{cite journal|last=Cucinotta|first=FA|coauthors=Schimmerling, W; Wilson, JW; Peterson, LE; Badhwar, GD; Saganti, PB; Dicello, JF|title=Space radiation cancer risks and uncertainties for Mars missions|journal=Radiation research|date=Nov 2001|volume=156|issue=5 Pt 2|pages=682–8|pmid=11604093|jstor=3580473|doi=10.1667/0033-7587(2001)156[0682:SRCRAU]2.0.CO;2}}</ref>

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 <ref name="NCRP 1997a">{{cite book|last=NCRP|title=NCRP Report No. 126, Uncertainties in Fatal Cancer Risk Estimates Used in Radiation Protection|year=1997|publisher=NCRP|location=Bethesda, Md|url=http://www.ncrponline.org/Publications/Press_Releases/126press.html}}</ref> 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 [http://www.ncrponline.org/ National Council on Radiation Protection and Measurements (NPRC)] <ref name="NCRP 2000" /> 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.<ref name="Bunger 1981">{{cite journal|last=Bunger|first=BM|coauthors=Cook, JR; Barrick, MK|title=Life table methodology for evaluating radiation risk: an application based on occupational exposures|journal=Health physics|date=Apr 1981|volume=40|issue=4|pages=439–55|pmid=7228696|url=http://journals.lww.com/health-physics/Abstract/1981/04000/Life_Table_Methodology_for_Evaluating_Radiation.2.aspx|doi=10.1097/00004032-198104000-00002}}</ref><ref name="144-145">{{cite web|last=Cucinotta|first=F.A.|title=Risk of Radiation Carcinogenesis|url=http://humanresearchroadmap.nasa.gov/evidence/reports/Carcinogenesis.pdf|work=Human Health and Performance Risks of Space Exploration Missions Evidence reviewed by the NASA Human Research Program|publisher=NASA|accessdate=8 June 2012|coauthors=Durante, M.|pages=144–145}}</ref>

For a homogenous population receiving an effective dose E at age a<sub>E</sub>, 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<sub>E</sub>,a)'', as:<ref name=144-145 />

::<math>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]}</math>

The survival probability to age, ''a'', following an exposure, ''E'' at age ''a<sub>E</sub>'', is:<ref name=144-145 />

::<math>S(E,a_E,a)= \prod_{u=a_E}^{a-1} \left[ 1-q(E,a_E,u)\right]</math>

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:<ref name=144-145 />

::<math>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)</math>

A minimum latency-time of 10 years is often used for low-LET radiation.<ref name="NCRP 2000" />  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:<ref name=144-145 />

::<math>REID=\sum_{a=a_E}^\infty m(E,a_E,a)S(E,a_E,a)</math>

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:<ref name=144-145 />

::<math>LLE=\sum_{a=a_E}^\infty S(0,a_E,a) - \sum_{a=a_E}^\infty S(E,a_E,a)</math>

The loss of life-expectancy among exposure-induced-deaths (LLE-REID) is defined by:<ref name=144-145 /><ref name="Vaeth 1990">{{cite journal|last=Vaeth|first=M|coauthors=Pierce, DA|title=Calculating excess lifetime risk in relative risk mdels|journal=Environmental Health Perspectives|year=1990|volume=81|pages=83–94|jstor=3431010|doi=10.1289/ehp.908783}}</ref>

::<math>LLE-REID=\frac {LLE}{REID}</math>

===Uncertainties in Low-LET Epidemiology Data===
The low-LET mortality rate per Sievert, ''m<sub>i</sub>'' is written<br>
::<math>m(E,a_x,a) = \frac {m_0 (E,a_x,a)}{DDREF} \frac {x_D x_s x_T x_B}{x_{Dr}}</math>
where ''m<sub>0</sub>'' is the baseline mortality rate per Sievert and ''x<sub>α</sub>'' are quantiles (random variables) whose values are sampled from associated probability distribution functions (PDFs), ''P(X<sub>a</sub>)''.<ref name=145-147>{{cite web|last=Cucinotta|first=F.A.|title=Risk of Radiation Carcinogenesis|url=http://humanresearchroadmap.nasa.gov/evidence/reports/Carcinogenesis.pdf|work=Human Health and Performance Risks of Space Exploration Missions Evidence reviewed by the NASA Human Research Program|publisher=NASA|accessdate=8 June 2012|coauthors=Durante, M.|pages=145–147}}</ref>

[http://www.ncrponline.org/Publications/Press_Releases/126press.html NPRC in Report No. 126] defines the following subjective PDFs, ''P(X<sub>a</sub>)'', for each factor that contributes to the acute low-LET risk projection:<ref name=145-147 />
# ''P<sub>dosimetry</sub>'' is the random and systematic errors in the estimation of the doses received by atomic-bomb blast survivors.
# ''P<sub>statistical</sub>'' is the distribution in uncertainty in the point estimate of the risk coefficient, ''r<sub>0</sub>''.
# ''P<sub>bias</sub>'' is any bias resulting for over- or under-reporting cancer deaths.
# ''P<sub>transfer</sub>'' is the uncertainty in the transfer of cancer risk following radiation exposure from the Japanese population to the U.S. population.
# ''P<sub>Dr</sub>'' 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.<ref name="155-161">{{cite web|last=Cucinotta|first=F.A.|title=Risk of Radiation Carcinogenesis|url=http://humanresearchroadmap.nasa.gov/evidence/reports/Carcinogenesis.pdf|work=Human Health and Performance Risks of Space Exploration Missions Evidence reviewed by the NASA Human Research Program|publisher=NASA|accessdate=6 June 2012|coauthors=Durante, M.|pages=155–161}}</ref>

The cancer risk projection for space missions is found by <ref name=155-161 /><br>
::<math>m_J(E,a_E,a)_{lJ}(E,a_E,a) \int dL \frac{dF}{dL}LQ_{trial-J}(L)X_{L-J}</math>
where <math>\frac{dF}{dL}</math> 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<sub>j</sub>(E)'', for each ion, ''j'', can be used <ref name=155-161 /><br>
::<math>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}</math>.

The result of either of these equations is inserted into the expression for the REID.<ref name=155-161 />

Related probability distribution functions (PDFs) are grouped together into a combined probability distribution function, ''P<sub>cmb</sub>(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 10<sup>5</sup>), the results for the REID estimated are binned and the median values and confidence intervals are found.<ref name=155-161 />

The chi-squared (χ<sup>2</sup>) test is used for determining whether two separate PDFs are significantly different (denoted ''p<sub>1</sub>(R<sub>i</sub>)'' and ''p<sub>2</sub>(R<sub>i</sub>)'', respectively).  Each ''p(R<sub>i</sub>) follows a Poisson distribution with variance <math>\sqrt{p(R_i)}</math>.<ref name=155-161 />

The χ<sup>2</sup> test for n-degrees of freedom characterizing the dispersion between the two distributions is <ref name=155-161 /><br>
::<math>\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)}}</math>.

The probability, ''P(ņχ<sup>2</sup>)'', that the two distributions are the same is calculated once χ<sup>2</sup> is determined.<ref name=155-161 />

===Radiation Carcinogenesis Mortality Rates===
Age- and gender-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.<ref name="NCRP 2000" />  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.<ref name="NCRP 2000" />

The radiation mortality rate is defined as:

::<math> m(E,a_E,a)=\left[ERR(a_E, a)M_c(a)+(1-v)EAR(a_E,a)\right]{\frac{\sum_LQ(L)F(L)L}{DDREF}}</math>

Where:<br>
::ERR = excess relative risk per Sievert
::EAR = excess additive risk per Sievert
::M<sub>c</sub>(a) = the gender- 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,<ref name="Durante 2008" /> but will be needed for other long-duration missions to Mars and beyond.<ref name=155-161 /> On 31 May 2013, NASA scientists reported that a possible [[manned mission to Mars]] may involve a great [[radiation|radiation risk]] based on the amount of [[radiation|energetic particle radiation]] detected by the [[Radiation assessment detector|RAD]] on the [[Mars Science Laboratory]] while traveling from the [[Earth]] to [[Mars]] in 2011-2012.<ref name="SCI-20130531a" /><ref name="SCI-20130531b" /><ref name="NYT-20130530" /><ref name="SN-20130629" />

There are three fundamental ways to reduce exposure to ionizing radiation:<ref name=155-161 />
* increasing the distance from the radiation source
* reducing the exposure time
* shielding (i.e.: a physical barrier)

Since space radiation is omnidirectional, distance has no bearing in space.  Also, since the duration of space missions will only increase, reducing the exposure time is not a feasible option.

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 terrestrial radiation workers.  In space, high-energy radiation is very penetrating and the effectiveness of radiation shielding depends on the atomic make-up of the material used.<ref name=155-161 />

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.<ref name=155-161 />

==Benefits to Earth==
{{Empty section|date=June 2012}}

==Evidence Sub-pages==
The evidence and updates to projection models for cancer risk from low-LET radiation are reviewed periodically by several prestigious bodies, which include the following organizations:<ref name=127-131 />
* 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,<ref name="BIER 2006" /> 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.<ref name="NCRP 2000" /><ref name=127-131 /><ref name="NCRP 1989">{{cite book|last=NCRP|first=NCRP Report No. 98|title=Guidance on radiation received in space activities|year=1989|publisher=NCRP|location=Bethesda, Md.|url=http://www.ncrppublications.org/Reports/098}}</ref><ref name="NCRP 2006">{{cite book|last=NCRP|first=NCRP Report No. 153|title=Information needed to make radiation protection recommendations for space missions beyond low-Earth orbit|year=2006|publisher=NCRP|location=Bethesda, Md.|url=http://www.ncrponline.org/Publications/Press_Releases/153press.html}}</ref>

[[Epidemiology data for low-linear energy transfer radiation|Epidemiology data for low linear energy transfer radiation]]

[[Radiobiology evidence for protons and HZE nuclei]]

[[Radiation carcinogenesis in past space missions]]

==See also==
*[[Dosimetry]]
*[[Health threat from cosmic rays]]
*[[Radiation syndromes#Spaceflight|Radiation Syndrome]]
*[[Central nervous system effects from radiation exposure during spaceflight]]

==External links==
*{{cite journal |last1=Asaithamby |first1=A |last2=Uematsu |first2=N |last3=Chatterjee |first3=A |last4=Story |first4=MD |last5=Burma |first5=S |last6=Chen |first6=DJ |title=Repair of HZE-particle-induced DNA double-strand breaks in normal human fibroblasts |journal=Radiation Research |date=April 2008 |volume=169 |issue=4 |pages=437–46 |pmid=18363429 |doi=10.1667/RR1165.1}}
*{{cite journal |last1=Chatterjee |first1=A. |last2=Borak |first2=T.H. |title=Physical and biological studies with protons and HZE particles in a NASA supported research center in radiation health |journal=Physica Medica |year=2001 |volume=17 |issue=1 |pages=59–66 |url=http://www.physicamedica.com/VOLXVII_S1/13-CHATTERJEE-BORAK.pdf |accessdate=5 June 2012}}
*{{cite web |last=Snyder |first=Kendra |title=One-Two Particle Punch Poses Greater Risk for Astronauts |url=http://www.bnl.gov/bnlweb/pubaf/pr/pr_display.asp?prid=06-99 |publisher=Brookhaven National Laboratory |accessdate=6 June 2012 |date=August 2006}}
*{{cite journal |last1=Bucker |first1=H |last2=Facius |first2=R |title=The role of HZE particles in space flight: results from spaceflight and ground-based experiments |journal=Acta Astronautica |date=Sep–Oct 1981 |volume=8 |issue=9–10 |pages=1099–107 |pmid=11543100 |doi=10.1016/0094-5765(81)90084-9}}
*{{cite book |author=Committee on the Evaluation of Radiation Shielding for Space Exploration, Aeronautics and Space Engineering Board, Division on Engineering and Physical Sciences, National Research Council of the National Academies |title=Managing space radiation risk in the new era of space exploration |year=2008 |publisher=National Academies Press |location=Washington, D.C. |isbn=978-0-309-11383-0}}
* [http://three.usra.edu/ The Health Risks of Extraterrestrial Environments]

==References==
{{reflist|2}}

{{NASA|article=Human Health and Performance Risks of Space Exploration Missions|url=http://humanresearchroadmap.nasa.gov/evidence/reports/EvidenceBook.pdf|comment=NASA SP-2009-3405}}

{{Space medicine}}

[[Category:Space medicine]]