Tumour progression is more heavily influenced by environmental or extrinsic factors than by intrinsic factors, such as random errors during DNA replication, and it is important that these extrinsic factors are taken into account in cancer prevention and research, reports a new analysis published in Nature this week.

Cancers are thought to originate from normal tissue progenitor or stem cells that become malignant through the accumulation of mutations during cell division.

These mutations can result both from intrinsic processes, including random errors during DNA replication as cells divide, and extrinsic factors, such as ultraviolet radiation and carcinogens.

Recent research has shown a strong correlation between the risk of developing cancer in specific tissues and the total number of stem-cell divisions over a lifetime in those same tissues.

However, whether this correlation implies a high and unavoidable intrinsic cancer risk remains controversial.

Yusuf Hannun and colleagues provide evidence that intrinsic risk factors contribute modestly (less than ~10–30%) to cancer development.

Using the same data as a recent study that reported a correlation between stem-cell division and cancer risk, the authors show that this correlation does not account for the difference between the effects of intrinsic and extrinsic factors.

They then use epidemiological data, analysis of mutational signatures and theoretical modelling of intrinsic risk to conclude that cancer risk is heavily influenced (70–90%) by extrinsic factors.

Source: Nature