Cancer risk associated with low-dose ionizing radiation: A systematic review of epidemiological and biological evidence

The current radiation protection reference standards on stochastic cancer risk, drafted by the International Committee on Radiation Protection, are mostly based on the Life Span Study (LSS), though sufficient epidemiological and basic research evidence is lacking. The relationship between low-dose ionizing radiation (LDIR) and cancer risk is currently modeled with linear non-threshold (LNT) models. However, with the widespread use of medical examinations, the demand for substantial evidence of cancer risk under LDIR and the establishment of a threshold has become more significant. In the first part of the review, we summarize pivotal research in epidemiology, which includes the LSS, medical radiation studies, and occupational and environmental exposure studies. We describe and discuss solid cancers and hematopoietic malignancies induced by LDIR separately, attempting to identify the consistency and differences in the research results, and offering suggestions for future research directions. In the second part, we review recent progress in the underlying biology of cancer associated with LDIR. Besides the obvious harmful effect of DNA damage, chromosome aberrations caused by LDIR, epigenetic regulation also requires attention due to their relationship with carcinogenic and genetic risk. The multistage carcinogenesis model of stem cells, along with the varying effects of radiation on different tumors, may challenge the LNT model. Related research of stem cells, mitochondria and omic biology also offers promising directions for future research in this field.