Our understanding of the causes of cancer has made considerable strides in recent years, and improvements in early identification, treatment, and prevention have reduced cancer mortality in industrialised nations. Despite these advancements, many tumours are still spreading around the globe. Further evidence suggests that a large portion of cancer risk is due to factors other than the unavoidable intrinsic DNA replication errors that are common to all humans, which we define as the “intrinsic risk,” as shown by the notable differences in age-adjusted cancer incidence rates for nearly all cancers across various regions of the world.
The search for cancer risk factors has taken many years, and extensive efforts are still being made in this area.
Intrinsic Risk Factors
According to the definition given above, intrinsic risk develops when there are no non-intrinsic factors present and the basal mutation rate is active in all proliferating cells. Thus, unlike other sources of non-intrinsic factors that may vary between individuals, this risk is “fixed” on all humans.
The technological incapacity to accurately distinguish between the impacts of intrinsic errors and non-intrinsic factors in people presents a hurdle to the direct calculation of intrinsic error to cancer risk. Modeling studies of cancer development based on experimental/clinical data have historically been the main source of evidence supporting intrinsic risk in cancer. The ability to examine genome-wide somatic mutations in cancer has undergone a radical change as a result of the recent introduction and quick development of next-generation DNA sequencing technology.
