Seminario - Cancer: "bad luck" or environment? The contribution of exposome research. Relatore: Prof. Paolo Vineis
Venerdì 24 novembre nell'aula BS di Via Celoria 26 (Milano) alle 14
Relatore: Paolo Vineis, Imperial College of London
In March 2017 Science published a new paper by Tomasetti et al. which is a follow-up to their first 2015 paper. Both papers were accompanied by headlines in many media and social media reading “Most Cancer Cases Arise from "Bad Luck"” or “'Bad luck' mutations increase cancer risk more than behavior, study says” . There are several reasons to reject these claims. According to the two papers, normal stem cell lifetime divisions are correlated with cancer development and, at a molecular level, a large fraction of stem cell mutations would occur randomly.
First, we (Vineis et al, submitted) have shown that the correlation between mutation rates in the cells of smokers and cancer incidence in smokers is much more evident than the association of the latter with stem cell lifetime divisions. The correlation coefficient for the association between the cancer incidence hazard ratio for smokers and mutation rates (per pack year) in smokers is ρ=0.93, with significant trend (p=0.0207). The correlation coefficient is ρ=-0.65 when we compare the cancer incidence hazard ratio with cumulative stem cell divisions, with a non-significant negative trend (p=0.2319). In summary, although based on a small number of cancer endpoints, it appears that smoking-induced mutations are more likely to be related to smoking-associated cancer risk than smoking-associated cancer risk is to cumulative stem cell lifetime divisions.
Second, on a global scale cancers show great disparities and relatively rapid changes in incidence. During the 20th century in the US, risk for lung cancer increased by more than 50 fold but it decreased by about ten-fold for cervix and stomach cancers. Liver cancer incidence rates in males (number of newly diagnosed cancer cases per 100,000 males per year) range from 2 in Iceland to almost 100 in Mongolia. There is clear evidence that cancer is essentially an environmental disease and bad luck is not the main explanation.
Third, in Tomasetti et al a whole other aspect of the carcinogenic process is missing: non-genotoxic alterations at the cellular level as expressed e.g. in the “hallmarks of cancer” paradigm (Kelly-Irving et al, in press). In fact, mutations are necessary, but not sufficient. I will present the principles and practice of “exposome” research, aimed at improving our knowledge of the mechanisms that mediate the impact of environmental exposure on cancer risk.
INFO: Prof. Giulio Costantini