DNA mutation from spaceflight may increase cancer risk in astronauts

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Fourteen astronauts from NASA's space shuttle program who flew between 1998 and 2001 on shuttle missions averaging 12 days took part in a study on DNA mutations, with 85% being male and six on their first mission for the space agency. 

Researchers in a study published on August 31 in Nature Communications Biology sampled whole blood from the astronauts twice, 10 days before spaceflight and on the day of landing, and white blood cell samples were collected once, 3 days after landing. Those samples were placed in a freezer at minus 112 degrees Fahrenheit and left untouched for 20 years.

The study’s lead author, David Goukassian, who is a professor of cardiology with the Cardiovascular Research Institute at Icahn Mount Sinai in New York, commented in a statement that "astronauts work in an extreme environment where many factors can result in somatic mutations, most importantly space radiation, which means there is a risk that these mutations could develop into clonal hematopoiesis."

Somatic mutations are a type of mutation that occurs after a human is conceived but in cells other than the sperm or egg cells, which means that they cannot be passed on to future generations. Clonal hematopoiesis is the overrepresentation of blood cells derived from a single clone, which characterized the mutations identified in the study. Different blood cancers, such as chronic myeloid leukemia, are examples of clonal hematopoiesis.

"Given the growing interest in both commercial spaceflights and deep space exploration, and the potential health risks of exposure to various harmful factors that are associated with repeated or long-duration exploration space missions, such as a trip to Mars, we decided to explore, retrospectively, somatic mutation," Goukassian explained. 

In addition to bioinformatics analysis, scientists used DNA sequencing to identify 34 mutations in 17 clonal-hematopoiesis-driver genes, finding that the most common mutations occurred in TP3, a gene that produces a tumor-suppressing protein, and DNMT3A, one of the most frequently mutated genes in acute myeloid leukemia.

Even though the mutations were considerably high for the astronauts' ages, the researchers argued it was still below a worrying threshold, with Goukassian noting that the presence of the mutations does not necessarily indicate the development of cardiovascular cancer but the risk could increase with "prolonged exposure to the extreme environment of deep space".

This follows as NASA speeds up its long-delayed Artemis program (which was postponed for the second time due to technical issues) to put America on the lunar surface for the first time in 50 years, but these types of health observations for astronauts will be a key to the future success of spaceflight to the moon, Mars, and beyond. 

According to the researchers, they concluded their ability to conduct this type of study to examine astronauts' vulnerability to disease without impacting their ability to work, recommending that NASA and its medical team can screen astronauts for somatic mutations and possible clonal expansion, or regression, every three to five years, and following into their retirement years - when these types of mutations can potentially expand. 

Goukassian further stressed the importance of conducting "longitudinal retrospective and well-controlled prospective studies involving a large number of astronauts" in order to monitor the evolution of the risk "based on continued exposure" and comparing the data with "their clinical symptoms, imaging, and lab results." He added, "That will enable us to make informed predictions as to which individuals are more likely to develop a disease based on the phenomena we are seeing and open the door to individualized precision medicine approaches to early intervention and prevention."

This work comes after a study in 2017 involving 17 astronauts before and after spaceflight over seven years demonstrated signs of incomplete bone recovery in astronauts who partake in spaceflights lasting longer than three months even after a full year on Earth, as Leigh Gabel, assistant professor in Kinesiology and lead author of the study said in a statement, " This suggests the permanent bone loss due to spaceflight is about the same as a decade worth of age-related bone loss on Earth."

Researchers went to Johnson Space Center in Houston, Texas, and scanned the wrists and ankles of the astronauts before they left for space and 1 year after returning from spaceflight. Most astronauts demonstrated incomplete recovery of bone density, strength, and trabecular thickness at the weight-bearing distal tibia.