I was quite surprised to find this in one of the most prestigious journals in the world. Vogelstein is one of the biggest names in cancer research, and no doubt that was the most important factor in its publication.
Some problems:
1. They leave out breast cancer and prostate cancer, two of the most common cancers out there. Most of the dots on their plot relate to a tiny proportion of cancers that people get. Furthermore, breast cancer has a very low mutation rate, which also casts doubt on their hypothesis about accummulation of somatic mutations on stem cells.
2. I ran their data using just the number of stem cells and the number of cells versus incidence. The correlations are still good, about 0.5 for just cell mass and 0.67 for number of stem cells. It's hardly a revelation that a larger more cellular organ is more likely to get cancer.
3. For glioblastoma, a type of brain tumour, their data says that there are 0 stem cell divisions, because it is thought there is no cell renewal in the brain (which isn't even true, but anyway). This contradicts the whole hypothesis, but they still include it in there.
4. The lifetime incidence of various cancers is age dependent. For example sarcomas almost always occur in the young, medulloblastoma is vanishingly rare in the elderly, testicular cancer occurs in young men. Their hypothesis ignores all this, because their model only allows for the acquisition of mutations over time, which should give a unimodal relationship between age and cancer incidence.
5. There are cancers that have almost no mutations. Gene copy number changes are just as important if not more so than mutations. There is very little evidence that copy number changes accumulate over time in stem cells in a random fashion required by this model.
I don't think this warrants much attention in the end. This can join the 100,000 other unverified (or unverifiable correlations) in the cancer literature.
Some problems: 1. They leave out breast cancer and prostate cancer, two of the most common cancers out there. Most of the dots on their plot relate to a tiny proportion of cancers that people get. Furthermore, breast cancer has a very low mutation rate, which also casts doubt on their hypothesis about accummulation of somatic mutations on stem cells.
2. I ran their data using just the number of stem cells and the number of cells versus incidence. The correlations are still good, about 0.5 for just cell mass and 0.67 for number of stem cells. It's hardly a revelation that a larger more cellular organ is more likely to get cancer.
3. For glioblastoma, a type of brain tumour, their data says that there are 0 stem cell divisions, because it is thought there is no cell renewal in the brain (which isn't even true, but anyway). This contradicts the whole hypothesis, but they still include it in there.
4. The lifetime incidence of various cancers is age dependent. For example sarcomas almost always occur in the young, medulloblastoma is vanishingly rare in the elderly, testicular cancer occurs in young men. Their hypothesis ignores all this, because their model only allows for the acquisition of mutations over time, which should give a unimodal relationship between age and cancer incidence.
5. There are cancers that have almost no mutations. Gene copy number changes are just as important if not more so than mutations. There is very little evidence that copy number changes accumulate over time in stem cells in a random fashion required by this model.
I don't think this warrants much attention in the end. This can join the 100,000 other unverified (or unverifiable correlations) in the cancer literature.