the benefits of Primary Prevention of colorectal cancer around the age of 20 comPared to secondary Prevention after the age of 50 ©

© К.А. Шемеровский 1, П.д. Шабанов 1, В.Ф. Митрейкин 2, П.В. селивёрстов 3, А.Ю. Юров 4 1 ФгБнУ «институт экспериментальной медицины», Санкт-Петербург; 2 ФгБоУ Во «Первый Санкт-Петербургский государственный медицинский университет им. акад. и.П. Павлова» Минздрава России, Санкт-Петербург; 3 ФгБоУ Во «Северо-Западный государственный медицинский университет им. и.и. Мечникова» Минздрава России, Санкт-Петербург; 4 ФгБоУ Во «Санкт-Петербургский государственный педиатрический медицинский университет» Минздрава России


INTRODUCTION
Colorectal cancer is a predominant cause of cancer morbidity in St. Petersburg, Russia.In 2015, the incidence of colon cancer increased by 34% with 3,654 newly diagnosed cases compared with the reported incidence in 2010 [2].It has been established that colorectal coprostasis, accompanied by chronic constipation, is a risk factor for the development of colorectal cancer (2.5-fold increase in risk) [5,11,14,15].
Inducers of colorectal cancer, namely, animal proteins, and red meat fats (particularly barbecue processed with open fire, grill, or shashlik), overweight, hypodynamia, excessive consumption of alcohol, and tobacco smoking are known to promote colorectal coprostasis [7,14].In contrast, protective risk factors for colorectal cancer stimulating the evacuation function of the intestine include vegetables, fruits, dietary fiber, fish, chicken meat, calcium, folates, vitamin D, antioxidants, biologically active food components, sufficient physical activity, and a normal level of sex hormones.
Recently, it was demonstrated that certain widely used laxatives (currently not produced in numerous Western countries) and unapproved medications (e. g., polyphenol laxatives and senna preparations) are considered risk factors for the development of colorectal cancer [6].Chronic constipation accompanied by colorectal coprostasis increases the risk of colon carcinoma from 1.36 to 4.4 times [15].
Modern approaches to the prevention of colorectal cancer is secondary (screening), mainly focusing on late manifestations of colon pathology, detection of blood in the feces, and the endoscopic removal of adenomatous polyps (precancerous colon formations) [1,14].It is recommended that screening should be initiated at the age >50 years, with colonoscopy and sigmoidoscopy performed once every 10 and 5 years, respectively [1].
According to colon cancer studies conducted in the USA and UK [6], the average age of colon cancer detection is approximately 63 and 68 years in women and men, respectively.In 2008, 55,719 newly diagnosed cases of colorectal cancer were recorded in Russia, with the mortality rate amounting to 37,901 cases [3].In the Northwestern Federal District, pediatricians have reported that nearly half (48%) of the children suffer from the earliest stages of constipation, a known risk factor for the development of colorectal cancer [14].
Academician N.N.Petrov in the clinical manual "Malignant tumors" emphasized the importance of habitual constipation in the occurrence of colon cancer, stating that "prevention of colon cancer is the prevention of constipation" [8].
Primary prevention of colorectal cancer should be aimed at diagnosing and eliminating the earliest stages of circadian rhythm disruption in the evacuation function of the intestine.Such prevention should be functional, non-invasive, and implemented as early as possible in the life of the patient.
The purpose of the current study was to describe the benefits of primary prevention of colorectal cancer in the form of prevention of early disruptions of the circadian rhythm of the intestine.

MATERIALS AND METHODS
The chronoenterography method involves weekly monitoring of the frequency and acrophase of the circadian rhythm of enteric evacuation activity of the colon [10].A total of 2,501 medical workers, aged between 24 and 75 years, were examined.
Screening for bradyenteria (slowing and disturbance in the regularity of the circadian rhythm of defecation) was performed.This disorder, indicating a tendency toward constipation, is one of the earliest manifestations of colorectal coprostasis.The severity of bradyenteria was defined on the basis of the defecation frequency, i. e., mild (5-6 times per week), moderate (3-4 times per week), and severe (1-2 times per week).
For early primary prevention of colorectal cancer, we screened for bradyenteria (slowing the circadian rhythm of defecation to <7 times a week).It was conducted as weekly monitoring of frequency and acrophase (the moment of implementation of the function in the diurnal period) of the circadian rhythm of defecation among medical institution students aged 19-20 (50 men and 81 women).For screening, a specially developed questionnaire was used to assess the frequency of the evacuation function of the intestine (number of days per week with acts of defecation), the number of bowel evacuations per day (number of acts of defecation within 24 h), and the acrophase of the circadian rhythm of defecation (the time of bowel evacuation in each of the four following periods of the daily 24-h cycle: 06:00-12:00, 12:00-18:00, 18:00-24:00, and 24:00-06:00).In addition, quality of life was investigated using the health, activity, and mood system [9].
In contrast, among those with an irregular rhythm of defecation, the evening acrophase was observed more frequently (1.5-fold difference) than the morning acrophase (667 vs. 435 cases, respectively).These findings showed that the acrophase of the circadian rhythm of the evacuation function of the intestine is a key mechanism for the regulation of the rhythm of defecation.
The predominance of the morning acrophase and evening acrophase was associated with the regular and irregular rhythm of It was revealed that 34% of young male doctors had irregular bowel rhythm, whereas 86% of the interviewed students did not have a physiologically optimal habit for morning bowel evacuation (Table 2).
Irregular enteral rhythm in the form of bradyenteria was diagnosed in 34% and 45% of male and female doctors, respectively.Moreover, only 14% and 20% of the male and female students were shown to have a physiologically optimal habit for morning bowel evacuation, 86% of the interviewed students do not have a physiologically optimal habit for morning bowel evacuation (Table 2).
The level of quality of life in individuals with a regular morning intestinal rhythm (94% of the optimal) was 8% higher than that in individuals with an irregular evening rhythm of the intestine (86% of the optimal).
Morning defecation (acrophasia of the defecation rhythm) was observed 6 times more often in male doctors with a regular bowel rhythm than those with an irregular bowel rhythm (bradyenteria with a defecation frequency of 1-6 times a week).Morning defecation in female students with a regular rhythm of the in- The habit of morning defecation contributes to its regularity and a higher level of quality of life.
In total, 45% of young female medical students have irregular bowel rhythm, whereas 80% of the students surveyed did not have a physiologically optimal habit of morning bowel evacuation.
The level of quality of life (87% of optimal) in women with regular intestinal rhythm was 11% higher than that in women with irregular bowel rhythm (76% of optimal).Repeated screening for bradyenteria (a month after acquaintance with the principle of circadian regularity of the brain and intestines) revealed that 53% of the individuals with moderate bradyenteria, determined during the first screening, strived to implement the circadian rhythm of defecation predominantly in the morning.This change in behavior led to improvement in the stage of bradyenteria severity from moderate (frequency of defecation, 3-4 times per week) to mild (frequency of defecation, 5-6 times per week) in more than half (53%) of the participants.This reduction in the severity of bradyenteria indicates that the regularity of the circadian rhythm of enteral activity may be improved through behavioral adjustments.
Two approaches for prevention of the risk of colorectal cancer should be compared, namely the primary functional prevention aimed at screening and elimination of bradyenteria (as a proven functional risk factor for colon cancer) and secondary organic prevention aimed at screening and endoscopic removal of adenomatous polyps (as a potential precancerous condition of the colon).
Studies involving screening and endoscopic prevention of colorectal cancer showed that complications occurring during colonoscopy include bleeding, colon perforations, and death (three deaths per 30,000 colonoscopies and seven deaths per 97,000 colonoscopies reported in two studies) [12,13].The total risk of complications during colonoscopy (gut examination without biopsy) and surgical colonoscopy (biopsy and removal of adenomatous polyps) is approximately 1% and 3%, respectively.
The new clinical recommendations established by the Russian Gastroenterological Association, headed by academician V.T. Ivashkin, are aimed at optimizing the diagnosis and treatment of patients with irritable bowel syndrome, and those with chronic constipation using drugs such as trimebutine and lactitol [4].

CONCLUSION
The main advantages of the primary prevention of colon cancer are non-invasiveness, harmlessness, absence of complications, and cost-effective.These advantages are based on the timely detection and elimination of known risk factors (such as chronic constipation.It is particularly important to identify the predecessor of constipation, bradyarrhythmia of the intestine, which is a disruption in the regularity According to the clinical recommendations [5] of the Russian Gastroenterological Association, a physiologically optimal habit of bowel evacuation in the morning, especially after breakfast, is essential from early childhood and throughout the life of the individual.