Establishing mechanisms affecting the individual response to ionizing radiation

Area of Science:

• Radiation biology
• Genetics
• Oncology

Background:

• Human exposure to ionizing radiation (IR) is increasing.
• Both low and high doses of IR can cause stochastic effects like cancer.
• Radiotherapy (RT) patients exhibit radiosensitivity (RS) and radiosusceptibility (RSu), with 10-15% experiencing adverse reactions.

Purpose of the Study:

• To review potential mechanisms contributing to radiosensitivity and radiosusceptibility.
• To focus on understanding radiosensitivity in radiotherapy patients.
• To optimize radiation protection strategies by understanding individual variability.

Main Methods:

• Literature review of mechanisms influencing radiosensitivity and radiosusceptibility.
• Analysis of the DNA damage response (DDR) in relation to adverse reactions.
• Discussion of genetic determination of radiosensitivity/radiosusceptibility.

Main Results:

• The DNA damage response (DDR) is well-characterized but mutations explain only a small fraction of radiosensitive radiotherapy patients.
• Additional factors beyond DDR significantly influence radiosensitivity and radiosusceptibility.
• The genetic basis of radiosensitivity/radiosusceptibility requires further investigation.

Conclusions:

• A prospective study is recommended to assess radiosensitivity following radiotherapy.
• Future studies should include detailed tumor site, grading systems, and validated predictive assays.
• Investigating inflammatory, stress, immune responses, mitochondrial function, and lifestyle factors is essential.