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Connections in Cancer: How stem cells impact cancer risk Augustana Houcek
Lake Forest College
Lake Forest, Illinois 60045
Cancer is often a life-threatening disease that affects a large number of people each year. According to the National Cancer Institute’s website, it is estimated that in 2018 alone, over 1.8 million people were diagnosed with cancer and half a million people died. Up until now, it was not very well known what causes certain types of cancers and what the chances are of developing certain types of cancer. There are obvious contributors, such as smoking, obesity, and age, which all increase the likelihood of developing cancer to some degree.
Hereditary genetics account for 5 to 10% of cancers, and environmental factors can account for some of the reasons individuals develop cancer as well, but not in all incidences. The current working theory of cancer development is that many of the genetic changes that result in the development of cancer occur randomly, as opposed to being the result of carcinogenic factors. Since the mutation rate of most human cell types is similar, some scientists predict that there would be a correlation between the number of stem cell divisions in each organ, and the risk of developing cancer in that particular organ.
Researchers Cristian Tomasetti and Bert Vogelstein tested this prediction, by identifying organ tissues in which there was already some knowledge on the stem cell dynamics that occur, such as the number of replications that take place. Through this identification process, they were able to find 31 tissue types in which these types of quantifications were assessed.
First, the researchers wanted to distinguish the relationship between the number of stem cell divisions over the average human lifespan, and the general lifetime risk of cancer development in each organ. Figure 1 shows a graph in which the x-axis shows the total number of stem cell divisions over the average lifetime of a human, and the y-axis shows the lifetime risk of cancer development in that particular organ. This graph spans across five orders of magnitude, and therefore is applicable to cancers that have large differences in incidence.
This figure boasts a pearson correlation of .805, meaning that 65% of the differences in the risk of cancer can be explained by the number of stem cell divisions in those particular tissues. This suggests that a major contributor of cancer in humans can be explained by the stochastic, or random, effects of DNA replication.
Secondly, the researchers wanted to distinguish these DNA replications from other causative factors. Other causative factors can include environmental factors and inherited DNA mutations, amongst other things. This would allow the researchers to more precisely identify exactly how much of the cancer risk stems from stem cell replications alone. Figure 2 shows a newly defined variable, ERS, or “extra risk score.” The ERS was calculated by finding the product of the lifetime risk of developing a type of cancer and the number of stem cell divisions that take place over the average human lifespan.
If the ERS is high, such as that found in the blue on the right side of the graph, tumors that developed are referred to as “d-tumors.” “D-tumors,” or deterministic tumors, are classified in this research as those that are strongly affected by environmental risks and/or hereditary factors. Those that have a lower ERS score, known as “r-tumors,” are regarded as being strongly affected by random error during DNA replication. The contribution of environmental and hereditary factors to r-tumors is minimal, and d-tumors have a replicative baseline, which environmental and hereditary factors compound on.
This research supports the idea that there is indeed a stochastic factor in cancer cell DNA replication, and that it plays a major role in a person’s risk of developing cancer. This factor, along with the analyses of “d” and “r” type tumors, allows for better insight into potential treatment methods for individual types of cancers. For example, d-tumors could be more easily prevented through primary prevention methods; also, in the example of d-tumors, secondary prevention methods could also further reduce the risk of developing these types of cancers.
The researchers concluded that for r-tumors it is likely that primary prevention methods would be less effective, as the occurrence of these types of cancers is contributed more to stochastic factors. Secondary prevention methods would be a more effective method of preventing these types of cancers. This information could have important public health implications and may allow us to find better and more effective ways to treat or prevent cancer.
Tomasetti, C. and Vogelstein, B. (2019). Variation in cancer risk among tissues can be explained by the number of stem cell divisions. ScienceMag.
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