A study published in Science (2017) investigates the relationship between normal stem cell divisions and cancer risk across 69 countries. The research found a strong correlation (median = 0.80) between cancer incidence and the number of stem cell divisions in various tissues, regardless of environmental factors. This suggests that random mutations during DNA replication (R) play a major role in cancer etiology, contributing to two-thirds of mutations in human cancers. The study also highlights the importance of early detection and prevention strategies, as many cancers arise from unavoidable R mutations. The study analyzed data from 423 cancer registries and found that the correlation between stem cell divisions and cancer risk was statistically significant in all countries. The results support the idea that R mutations are a major source of cancer mutations, even though environmental (E) and hereditary (H) factors also contribute. The study used a theoretical example to illustrate that even if most cancers could be prevented by reducing environmental exposure, a significant portion of mutations would still be due to R. The study also examined specific cancer types, such as lung adenocarcinoma and pancreatic ductal adenocarcinoma, and found that a large fraction of mutations in these cancers are due to R. For lung adenocarcinoma, 35% of driver gene mutations were attributed to factors unrelated to E or H, suggesting they are due to R. For pancreatic ductal adenocarcinoma, 77% of mutations were attributed to nonenvironmental and nonhereditary factors, likely R. The study emphasizes that while environmental factors can prevent a significant portion of cancers, R mutations remain a major contributor. The findings have important implications for cancer prevention and early detection strategies. The study also highlights the need for further research into the role of R mutations in cancer etiology and prevention. The results are consistent with epidemiological estimates of the fraction of cancers that can be prevented by changes in the environment.A study published in Science (2017) investigates the relationship between normal stem cell divisions and cancer risk across 69 countries. The research found a strong correlation (median = 0.80) between cancer incidence and the number of stem cell divisions in various tissues, regardless of environmental factors. This suggests that random mutations during DNA replication (R) play a major role in cancer etiology, contributing to two-thirds of mutations in human cancers. The study also highlights the importance of early detection and prevention strategies, as many cancers arise from unavoidable R mutations. The study analyzed data from 423 cancer registries and found that the correlation between stem cell divisions and cancer risk was statistically significant in all countries. The results support the idea that R mutations are a major source of cancer mutations, even though environmental (E) and hereditary (H) factors also contribute. The study used a theoretical example to illustrate that even if most cancers could be prevented by reducing environmental exposure, a significant portion of mutations would still be due to R. The study also examined specific cancer types, such as lung adenocarcinoma and pancreatic ductal adenocarcinoma, and found that a large fraction of mutations in these cancers are due to R. For lung adenocarcinoma, 35% of driver gene mutations were attributed to factors unrelated to E or H, suggesting they are due to R. For pancreatic ductal adenocarcinoma, 77% of mutations were attributed to nonenvironmental and nonhereditary factors, likely R. The study emphasizes that while environmental factors can prevent a significant portion of cancers, R mutations remain a major contributor. The findings have important implications for cancer prevention and early detection strategies. The study also highlights the need for further research into the role of R mutations in cancer etiology and prevention. The results are consistent with epidemiological estimates of the fraction of cancers that can be prevented by changes in the environment.