Question in photo **Article Summary: Cancer Risks and Influencing Factors**A study by Tomasetti and Vogelstein (2015) concluded that cancer risks are mainly due to random mutations, correlating strongly with the total number of cellular divisions. Conversely, a subsequent research team led by Wu et al. (2016) suggested that environmental factors significantly influence cancer development.**Intrinsic vs. Extrinsic Factors:**Wu et al. (2016) presented the following insights:- **Intrinsic Processes:** These include mutations from random errors during DNA replication, leading to malignant transformations.- **Extrinsic Factors:** These are environmental influences affecting mutagenesis rates, such as UV radiation, ionizing radiation, and carcinogens. Extrinsic factors like radiation can cause DNA damage that impacts cancer development post-cell division. They contribute to genetic alterations during cell division, enhancing cancer risk.Cancer risk emerges from seemingly uncontrollable intrinsic processes and preventable extrinsic factors.**Figure Description:**The diagram illustrates the interplay between intrinsic processes and extrinsic factors affecting cancer risks through stem-cell division. There are two main arrows in the schematic:1. **Arrow 1:** Shows the effect of intrinsic processes leading to stem-cell division.2. **Arrow 2:** Illustrates the role of extrinsic factors affecting stem-cell division.Both intrinsic and extrinsic factors contribute to cancer risk, as indicated by the schematic arrows.**Research Consideration:**The text challenges how a research team could distinguish the impact of environmental factors from the number of cell divisions affecting cancer risk. Results indicating substantial environmental impacts would suggest extrinsic factors are more significant, whereas high cell division impacts would point to intrinsic factors as the primary influence.**References:**- Tomasetti, C., & Vogelstein, B. (2015). Variation in cancer risk among tissues can be explained by the number of stem cell divisions. *Science, 347*(6217), 78–81. doi:10.1126/science.1260825- Wu, S., Powers, S., Zhu, W., & Hannun, Y. A. (2016). Substantial contribution of extrinsic risk factors to cancer development. *Nature, 529*(7584), 43–47. [http://dx.doi.org/10.1038/nature16166](http://dx.doi.org/10.1038/nature16166)

Cancer is simply uncontrolled multiplication of cells. Cells normally have a limit to the number of…

3. A paper by Tomasetti and Vogelstein (2015) claimed that cancer risks are largely due to random mutations, which is correlated to total lifetime number of cellular divisions. A second research team (Wu et al., 2016) claimed that there is actually a substantial effect of extrinsic (environmental) factors on the development of cancers. Here is some information from Wu et al (2016): "We made the conservative and yet conventional assumption that errors occurring during the division of cells, being routes of malignant transformation, can be influenced by both intrinsic processes as well as extrinsic factors (Fig. 1). 'Intrinsic processes' include those that result in mutations due to random errors in DNA replication, whereas 'extrinsic factors' are environmental factors that affect mutagenesis rates (such as ultraviolet (UV) radiation, ionizing radiation and carcinogens). For example, radiation can cause DNA damage, which would primarily result in deleterious mutations with functional consequences on cancer development only after cell division. Therefore, extrinsic factors may act through the accumulation of genetic alterations during cell division to increase cancer risk. Accordingly, cancer risk would result from those apparently uncontrollable intrinsic processes (Fig. 1, arrow 1) as well as from those highly modifiable and thus preventable extrinsic factors (Fig. 1, arrow 2)." Figure 1: Schematic showing how intrinsic processes and extrinsic factors relate to cancer risks through stem-cell division. 1 Intrinsic processes Stem-cell division Extrinsic factors Cancer risk This hypothesis maintains the strong role of stem-cell division in imparting cancer risk, but it also illustrates the potential contributions of both intrinsic and extrinsic factors operating through stem-cell division. Other effects, f... If you were part of the Wu et al. research team, how might you go about determining if it was environmental factors or number of cell divisions that increased cancer risk? What results would suggest that extrinsic (environmental) factors do have a substantial impact on cancer risks? In contrast, what results would support that intrinsic factors (e.g. number of cell divisions) is a more substantial factor for cancer risk?