Cancer: Inherited and Enviromentally-induced mutations. Is that all?

Conventional cancer biology stated for decades that nature and nurture are exclusively responsible for cancer formation and progression. Several milestones in etiology and prevention have been achieved and thus, the overall cancer mortality have dropped remarkably. However, this model had several pitfalls and was proven inadequate to explain cancer etiology. 

(©Jason Tasoulas 2017. Reproduction is not allowed without written permission)

Tomasseti et al., published recently a very interesting study, proposing a third determinant of cancer formation. More specifically, the team from Baltimore evaluated the incidence of cancer in different countries and reported that despite the fact that different regions had different patterns of environmental exposure, all cohorts presented strong correlation between the number of stem cell divisions and the risk of cancer. Based on this observation they developed a theoretical model based on genome-wide sequencing (GWS) and epidemiological data, to evaluate the role of random mutations during stem cell divisions, in cancer formation.

 (Reproduced from: https://opentextbc.ca/anatomyandphysiology/)

Interestingly, according to their model a significant fracture of cancers is related to neither hereditary nor environmental factors. These neoplasms –which according to conservative assumptions account for approximately one third of all malignancies- arise from random mistakes of dividing stem cells, during DNA replication. This theory is not opposed to what is already known regarding cancer etiology. On the contrary, it is complementary to the current knowledge and explains some paradoxical observations which were previously hard to understand. For instance, the incidence of neoplasms strongly related to environmental factors (e.g. lung adenocarcinoma and tobacco consumption) never drops to zero, even in non-exposed populations. The implementation of drastic lifestyle changes (e.g. quit of smoking and alcohol consumption, Mediterranean diet, regular exercise) is not always sufficient to determine or affect 100% the risk of cancer. In addition, some neoplasms are only mildly associated to environmental or hereditary factors and thus, their etiology is unclear. 

(Reproduced from: http://www.whatisepigenetics.com)

According to the authors, their model provides a reasonable explanation for the pathogenesis of malignant tumors, where the alterations in driver genes cannot be attributed to inheritance or environmental exposure. These findings indicate that cancer researchers maybe should study further the role of random mutations in different neoplasms and determine to which extent they contribute on cancer formation. 

At present, these alterations are unpreventable, but if this theory is validated, they could represent a future target for cancer prevention and therapy.