Numerous studies have focused on the effects of certain exposure factors on CRC events, however, few of these studies have applied the exposome theoretical framework to explore the synergy between these factors in relation to CRC development. To bridge this knowledge gap, this study used UKB data to explore the relationship between exposome factors and the risk of CRC by using evaluation measures with strong construct validity. This study has three noteworthy findings, based on the exposome theoretical framework. These results suggest that lifestyle, social, and ecosystem domains are related to the risk of CRC.
First, in terms of lifestyle domain, we found that a healthy lifestyle and less tobacco and alcohol use were associated with a reduced risk of CRC. These results are in agreement with those of previous studies (Carr et al., 2020; Cho et al., 2019; Choi et al., 2021; Huang & Liu, 2019). A healthy diet is considered to contain rich fish, fruits, vegetables, and less processed and red meat (Choi et al., 2021). This diet pattern included sufficient nutrition, and less fatty and carcinogenic substances, which could reduce the risk of CRC (Baena & Salinas, 2015). Obesity has a direct effect on certain hormone levels, such as insulin, oestrogen, and insulin-like growth factor-1, which produce a favourable environment for carcinogenesis (Perera et al., 2012). Physical activity can reduce CRC risk by motivating gut motility, benefiting the immune system, and elevating metabolic efficiency (Ruiz-Casado et al., 2017; Baena & Salinas, 2015). Alcohol metabolites, such as acetaldehyde, increased the risk of CRC, because acetaldehyde was evaluated as a carcinogen (Keum & Giovannucci, 2019). Smoking induces angiogenesis and suppresses cell-mediated immunity to facilitate tumour growth (Liang et al., 2019).
Second, in terms of social domain, this study suggested that lower SES and less social support were associated with an increased risk of CRC. The finding of a relationship between SES and CRC risk was consistent with that of previous studies. Higher incidences of CRC are related to greater social disadvantage (Efberg et al., 2008; Savijärvi et al., 2019; Haster et al., 2015). One possible reason is that low-SES people may have less rational health behaviour, know less about their symptoms, and communicate more poorly than high-SES people with health care staff (Frederiksen et al., 2008). In contrast, high-SES people have better access to health information (Frederiksen et al., 2008) and seek health services (Doubeni et al., 2012); they are more likely to have behavioural changes to a healthy lifestyle (Geyer et al., 2006) and thus reduce the risk of CRC. However, findings regarding the association between social support and the incidence of CRC have been inconsistent. One study found no significant relationships between social networks and CRC incidence (Bergelt et al., 2009), while Ikeda et al. (2013) found that lower social support was associated with a higher incidence of CRC among men. This study supports the finding that lower support was related to an increased risk of CRC. One possibility is that social support raises the esteem of individuals and makes them feel valued, therefore, they may take better care of themselves and be more receptive to preventative services (Ikeda et al., 2013; Coughlin, 2020). Additionally, social support reduces stress and depression. Fewer stress hormones reduce the risk of immune dysregulation caused by (Godbout & Glaser, 2006), thereby suppressing the environment for tumour initiation.
Third, in terms of the ecosystem domain, a better ecosystem was associated with a reduced risk of CRC. However, limited studies have evaluated the ecosystem and CRC incidence. Increasing studies have suggested that ecosystems play a role in the incidence of cancer (Datzmann et al., 2018; Porcherie et al., 2021). It is unclear how ecosystems influence the risk of CRC. One possibility was that a better ecosystem was related to a more covered natural environment, with less pollution and radiation (Safe and Healthy Life Expert, 2017). Pollutants in water (El-Tawil, 2010), poisonous heavy metals (García-Pérez et al., 2020) and radiation (Sun et al., 2016) are associated with an increased risk of CRC. Furthermore, a better ecosystem may provide a greener environment, which provides a venue for physical activity (Shanahan et al., 2016). Engaging in more physical activity can help reduce the risk of CRC (Keum & Giovannucci, 2019).
This study has several strengths. First, the results highlight the effects of the physical (ecosystem) and social environments (SES and social support) on CRC events. The majority of previous studies have focused on the influence of biological factors on CRC events while ignoring environmental effects. Second, because of the increased acceptance that non-genetic factors play a role in diseases, this study included the entire set of exposome factors from a holistic perspective. It also showed the whole mechanism of exposome factors on the risk of CRC at a macro level. Under the exposome framework, a broad approach for CRC prevention can be considered. Apart from promoting a healthy lifestyle among the population to prevent CRC, it is also important to take care of people with lower SES and less social support.
However, this study has several limitations. First, this study did not capture temporal changes in exposome factor changes (e.g. lifestyle and SES changes) due to the nature of the dataset. Future studies should use panel data to trace the impact of dynamic changes in exposome factors on CRC events. Second, there may be complex interactions between the four domains, which were not observed in detail in this study. Future studies should include mediation or pathway analysis to explore the interaction of lifestyle, social, ecosystem, and physical-chemical effects on the risk of CRC. Third, although our analyses controlled for various confounding factors, we may have overlooked other factors related to CRC due to the limitation of using secondary datasets. Future studies should use a combination of qualitative and quantitative methods to improve the robustness of the results.