Risk factors, prevention and screening of colorectal cancer: A rising problem

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide. The leading risk factors for CRC include male gender, age over 50, family history, obesity, tobacco smoking, alcohol consumption, and unhealthy diet. CRC screening methods vary considerably between countries and depend on incidence, economic resources and healthcare structure. Important aspects of screening include adherence, which can vary significantly across ethnic and socioeconomic groups. Basic concepts of CRC screening include pre-stratification of patients by identifying risk factors and then using fecal immunochemical test or guaiac-based fecal occult blood test and/or colonoscopy or radiologic imaging techniques. Technological capabilities for CRC screening are rapidly evolving and include stool DNA test, liquid biopsy, virtual colonography, and the use of artificial intelligence. A CRC prevention strategy should be comprehensive and include active patient education along with targeted implementation of screening.

Key Words: Colorectal cancer; Screening; Prevention; Risk factors; Colonoscopy; Fecal immunochemical test; Fecal occult blood test; Stool DNA test; Diet; Lynch syndrome

Core Tip: Colorectal cancer occupies a leading position in the structure of oncological pathology. In this regard, prevention and screening of intestinal neoplasms are given great attention. There are standard methods of colorectal cancer screening, which include fecal occult blood tests and colonoscopy. New approaches include the use of DNA fecal testing, liquid biopsy, virtual colonography and artificial intelligence. The choice of screening strategy depends on the incidence of colorectal cancer, the social and economic situation in a particular region.

TO THE EDITOR

Oncological diseases are the second most important cause of mortality among the population. According to forecasts, by 2030, mortality from cancer of various localizations will begin to exceed mortality from coronary heart disease[1]. Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer death worldwide. In 2020, there were more than 1.9 million new cases of CRC and 0.9 million deaths from this pathology[2]. Statistical analysis of the GLOBOCAN database made it possible to develop a model for the movement of the CRC incidence situation from 2020 to 2040. It is predicted that there will be 3.2 million cases of CRC worldwide in 2040, which is 63% more than in 2020 (2 million cases), provided that the incidence rates remain unchanged. By 2040, CRC mortality is predicted to increase by 73.4%, from 0.9 million deaths in 2020 to more than 1.6 million deaths in 2040[3]. In this regard, the social significance of CRC is now defined as an emerging public health problem[4].

RISK FACTORS AND PREVENTION OF CRC

The development of CRC is associated with the action of non-modifiable and modifiable risk factors. Personal medical data [gender, age, ethnicity, detection of adenomatous polyps in the intestine, presence of inflammatory bowel diseases (IBD)] and family history of diseases cannot be controlled by a person and are non-modifiable risk factors. Modifiable factors are associated with the characteristics of a person's lifestyle (obesity, tobacco smoking, alcohol consumption, unhealthy diet)[5-10].

With increasing morbidity and mortality, the need for active prevention of CRC is becoming very important. Recently, there has been growing attention to the use of nutrition to prevent cancer of various locations[11,12]. It is assumed that CRC can be largely prevented by increasing physical activity[13] and dietary modification, including reducing the consumption of fat, sugar, red and processed meat[14]. A number of modern studies indicate the ability of carrots, green leafy vegetables, pineapples, citrus fruits, papaya, mango, gooseberries[15], the Mediterranean diet; products containing sufficient amounts of calcium, iron, selenium, fish, whole grains[16], fiber[17] due to antioxidant, anti-inflammatory and chemopreventive properties to maintain a healthy colon environment. The authors of a meta-analysis selected 24 studies that combined 1068158 participants and found a decrease in the risk of CRC with high consumption of citrus fruits, apples, watermelons and kiwi fruits[18].

Epidemiological studies show that primary prevention of CRC (prevention of modifiable risk factors) consists of quitting smoking tobacco and drinking alcohol in medium and high doses, increasing physical activity, preventing or reducing weight in obesity, optimizing diet. Secondary prevention of CRC involves timely screening and removal of intestinal adenomas[19,20].

CRC SCREENING

Currently, two strategies are used for CRC screening: (1) Screening based on preliminary determination of risk factors, which allows selecting patients for further examination; and (2) Population screening based on a large-scale examination of individuals in a certain population using epidemiological methods[21].

There is some debate, in which, on the one hand, there is no doubt about the logical concept that screening is necessary to detect precancerous changes and early forms of cancer and to reduce mortality from CRC[22-25]. On the other hand, there is a point of view about significant difficulties in the practical implementation of effective CRC screening[26]. The use of CRC screening and local recommendations vary in different regions of the world and depend on the incidence of the disease, economic resources, healthcare structure and infrastructure involved in screening[27,28]. For example, in the United States, it is recommended to start screening at age 45 for patients with average risk[29]. European guidelines consider it appropriate to start screening at age 50 years[30]. In Japan, it is recommended to start screening for CRC at the age of 40 years[31].

Certain difficulties in screening assessment are associated with a significant diversity of strategic approaches and the introduction of new technologies. The authors of the systematic review found 88 CRC screening strategies that differed in the type of diagnostic technique, screening interval, and use of one or more diagnostic tests. At the same time, an annual fecal immunochemical test (FIT) was the most frequently used CRC screening strategy[32]. Recently, considerable attention has been paid to the use of artificial intelligence (AI) and machine learning to optimize screening measures[33]. AI is now used to a greater extent for processing medical images obtained during colonoscopy, imaging and morphological studies, which allows for standardization of methods and helps diagnose polyps and early signs of CRC[34-36]. The first results of the use of AI are optimistic, but raise questions about improving cooperation between medical experts and AI systems. It has been suggested that AI algorithms must evolve and be continually tested. There is no doubt that the balance between human experience and technological solutions will improve diagnostics and the quality of patient treatment[37,38]. It is already obvious that CRC screening will be accompanied by the processing of data on the diagnosis and treatment of other diseases, which will lead to a sharp increase in the size of the information base, and will also raise the question of involving AI[39]. Among other methods, attention is now being paid to the development of various intervals and screening methods for individuals with a medium and high risk of CRC[40], the use of stool DNA testing and various imaging and endoscopic diagnostic methods[27]. A modern meta-analysis demonstrates that the reduction in mortality as a result of CRC screening increases with a screening duration of more than 5 years[41].

The association of CRC with IBD and lynch syndrome deserves attention. The mechanism of the relationship between ulcerative colitis and Crohn’s disease with CRC is explained by the presence of chronic inflammation in the mucosa, which causes an increase in the process of cellular proliferation and the frequency of mutations of epithelial cells in patients with IBD[42]. In a meta-analysis of 13 trials that included about 45 thousand patients with IBD, the risk of CRC was increased 3-fold in patients with the disease compared to healthy individuals[43]. Colonoscopy is the optimal strategy for the prevention of CRC in patients with IBD[44]. The meta-analysis showed that in the group of individuals with IBD observed using colonoscopy, CRC occurred in 1.8% of patients, and in the group without colonoscopy in 3.2% of cases (P < 0.001)[45].

Lynch syndrome is a hereditary predisposition to CRC, which was first described by Lynch et al[46]. Lynch syndrome accounts for 3%-5% of all CRCs. The specific risk of neoplasms depends on the type of pathogenic variants of MMR genes (MLH1, MSH2, MSH6, EPCAM) and additional factors, which include obesity, tobacco smoking, and reduced physical activity. Given the cumulative risk of CRC, which can reach 48% in patients with Lynch syndrome[47], there are international recommendations that consider it appropriate to conduct genetic testing in all CRC patients up to 70 years of age[48,49]. Currently, the prevailing opinion is that regular colonoscopies are the optimal method for preventing CRC in individuals with lynch syndrome and should be performed depending on the genotype starting at the age of 20-25 years or 35 years every 2 years[48,50,51].

Patient adherence has a significant impact on the effectiveness of CRC screening. In the United States, adherence to screening is low in African Americans and Hispanics[52]. In the Asia-Pacific region, adherence to CRC screening also varies significantly and is 21.0% in South Korea and 62.9% in Thailand[53,54]. Barriers to participation in screening include high cost, lack of information about CRC, lack of confidence in the success of screening, adherence to fatalism, or simply fear of screening tests[55]. In this regard, improving the level of adherence to screening and choosing the optimal strategy may be an important aspect of the effectiveness of CRC screening[56].

As background information, we provide the recommendations of the American Cancer Society (ACS), which consider it necessary to begin screening in individuals with an increased risk of CRC starting at age 45 years, using highly sensitive stool tests and visual methods (colonoscopy, etc.). During the screening process, colonoscopy should be performed in all patients with positive stool tests. It is strongly recommended to begin regular screening in adults at age 50 years and older.

The ACS considers that it is reasonable for average-risk adults who are in good health and have a life expectancy of more than 10 years to continue CRC screening until age 75. Screening decisions for patients over age 75 are made on an individual basis.

ACS recommends the following screening methods for CRC: (1) FIT every year; (2) High-sensitivity guaiac-based fecal occult blood test (FOBT) every year; (3) Colonoscopy every 10 years; (4) Computed tomography colonography every 5 years; and (5) Rectosigmoidoscopy every 5 years[23].

Family history of CRC, presence of intestinal adenomas, increasing age, and male gender are suggested as factors increasing the risk of CRC[57,58]. Attention should be paid to symptoms of “red flags”: Abdominal pain, changes in stool habits, weight loss, anemia, rectal bleeding[59,60].

FIT has recently become more widely used for CRC screening than FOBT due to the use of antibodies to detect globin, which is independent of diet. Another advantage of FIT is that it can be tested in only one stool sample. A study in Italy showed a 22% reduction in CRC mortality when using FIT for two years[61]. Observational cohort studies have shown a 10% reduction in CRC incidence[62] and a 62% reduction in CRC mortality[63] with FIT for screening.

Colonoscopy is one of the most commonly used methods for CRC screening[64,65]. A prospective cohort study involving 89000 healthcare workers over 24 years concluded that systematic use of colonoscopy for screening results in a 68% reduction in CRC mortality compared to individuals without CRC screening[66]. A similar result was demonstrated in a four-country study in northern Europe with 5-year CRC screening in 84585 patients using colonoscopy[67]. The sensitivity of colonoscopy for the detection of intestinal adenomas larger than 1 cm and CRC is estimated at 95%[22,68]. When performing colonoscopy, it is recommended to pay close attention to the presence of adenomas or sessile serrated lesions[69].

CONCLUSION

In recent years, there has been an unfavorable trend in the epidemiological indicators of CRC in various countries around the world. It should be emphasized that CRC screening is one of the preventive measures aimed at reducing mortality from this pathology. Crucial to creating an effective CRC prevention program is its comprehensive nature, including information about CRC risk factors and optimizing lifestyle and nutrition to protect against the pathology development. CRC screening is rapidly developing, increasingly relying on innovative technologies, requires significant organizational and financial costs, and can significantly reduce mortality from CRC.