Elsevier

Clinical Colorectal Cancer

Volume 15, Issue 3, September 2016, Pages 195-203
Clinical Colorectal Cancer

Review
Colorectal Cancer: Epidemiology, Disease Mechanisms and Interventions to Reduce Onset and Mortality

https://doi.org/10.1016/j.clcc.2016.02.008Get rights and content

Abstract

Colorectal cancer (CRC) is a multifactorial disease resulting from lifestyle, genetic, and environmental factors. There are hereditary and non-hereditary CRC types; however, the majority are non-hereditary and mainly caused by somatic mutations in response to environmental factors. In past years, researchers have focused their attention on the mechanisms behind these factors and the methods of improving disease prevention and treatment. Improving the awareness of the population with regard to the benefits of a healthy lifestyle, including a balanced diet associated with exercise, could globally reduce CRC risk. The present review aims to address the current knowledge on CRC, taking into consideration the common molecular alterations upon different environmental and non-environmental factors, current and promising treatment interventions, and how all these factors may interact to positively or negatively influence CRC risk.

Introduction

Colorectal cancer (CRC) is a heterogeneous disease that occurs in the colon and the rectum, parts of the gastrointestinal system. The colon has 4 sections; the ascending, transverse, descending, and sigmoid colon, and the latter is where most CRC arise. The majority of CRC develop slowly from adenomatous polyps or adenomas.1 The intestinal epithelium has a high turnover rate, which makes it a hotspot for malignant transformations such as CRC. Vogelstein initially described the colorectal carcinogenesis model, stating that specific genetic events could result in morphological tissue changes.2 This model has been referenced for more than 20 years, and recently, several studies suggested that CRC is a consequence of an array of factors, which are not only inherited but also acquired over the life course of the individual. Different molecular markers are linked to CRC development and metastasis; for example, the metastatic potential of CRC could be related to cell adhesion molecules such as cadherins and catenins, that, when downregulated, could facilitate tumor cell detachment, thus mediating the prognosis of this cancer.3 The risk of developing CRC could also be associated with environmental, socioeconomic, and lifestyle factors. However, understanding all the mechanisms and the associations between these factors is not an easy task. Research conducted on the molecular basis of CRC carcinogenesis and how this can be influenced by the lifestyle of different populations around the world has been invaluable as a preventive strategy. Furthermore, the evolving field of molecular pathologic epidemiology has brought molecular and population science closer to the medical practice. It combines 2 traditional disciplines, epidemiology and pathology, that use different approaches to understand disease. This multidisciplinary investigation comprises the understanding of the different aspects involved in the carcinogenesis process, such as environmental/exogenous (eg, lifestyle) and endogenous (eg, genetic) factors, molecular pathological markers for tumor initiation, and progression and response to different types of treatments, which collectively have led to important studies, not only in CRC but also in other diseases.4 An example of an important study associated with molecular pathologic epidemiology research is one that describes how aspirin use is linked to a better prognosis and clinical outcome in PIK3CA-mutated CRC.5 Personalized medicine involving a multidisciplinary team is an important tool, which aims to target cancer therapies based on unique genetic patterns of the tumor and/or the patient.6, 7

In the following sections, we will discuss the current aspects on CRC biology and epidemiology and how the understanding of these aspects are important to build on more rational preventive and treatment measures.

Section snippets

Incidence and Mortality of CRC

According to the International Agency for Research on Cancer (IARC) estimates, in 2015, CRC accounted for 9.7% of all incident cancers in the world, with approximately 814,000 cases in men and 664,000 cases in women. That makes it the third most common cancer in men and the second in women, with a large difference between countries; currently, more than 45% of these cases occur in less developed regions.8 In recent years, there has been a decline in the incidence of CRC in adults older than 50

Genetic, Environmental, and Lifestyle Factors and Their Relationship to CRC Risk

There is no specific cause for CRC; nevertheless, different factors are involved. Economic development and the adoption of a Western lifestyle have increased the exposure to certain environmental and lifestyle factors, increasing the risk of developing the disease.14 While increasing age can affect the probability of developing this cancer, the risk is about 2 times higher in men than in women.15 In addition, a history of previous colon polyps, an inflammatory bowel disease such as ulcerative

CRC Treatment, Prevention, and Screening Methods

CRC can be classified into different molecular subtypes because scientific advances made it possible to detect the affected genes by different technologies including gene expression tools. This is important to stratify patients into good and poor-prognosis groups in order to select the appropriate treatments for each case. Also, the tumor microenvironment has to be taken in consideration, and 2 recent articles have discussed the importance of the stroma in promoting relapse and metastasis.76, 77

Conclusion

Extensive research has been done to elucidate the causes and the cellular and molecular mechanisms underlying CRC development. Its molecular complexity results from a broad spectrum of genetic and epigenetic alterations, making it a highly heterogeneous cancer type. Studies on lifestyle associated with CRC risk and prevention can still result in biased information, since it can be difficult to interpret epidemiologic studies coming from different populations around the world, which have genetic

Disclosure

The authors have stated that they have no conflicts of interest.

Acknowledgments

The authors would like to thank Fundação Ary Frauzino (Brazilian Cancer Foundation) and Ministério da Saúde (Brazil).

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