**9.1.3 Fats**

186 Cancer Prevention – From Mechanisms to Translational Benefits

Overweight Low physical activity Carbohydrates (long chained)

ovarian Ca, mammary Ca

large bowel polyp formation as well. High caloric intake in combination with low physical activity leads to hyperinsulinemia and peripheral insulin resistance, which could result in high mucosal proliferative activity, reduced apoptosis, accumulation of free radicals, and mutagenesis. Being overweight could have an inappropriate influence on the immune system, could elevate the serum level of prolactine, and raise the sensitivity of the hypothalamo-hypophyseal axis. High BMI and high caloric intake are connected with elevated risk for development of CRC and colorectal adenomas according to different

Food contains various food additives, contaminants, fertilizers, herbicides, food dying agents, antibiotics and antimycotics. Increased mutageneity has been observed in faeces of patients with elevated risk for CRC formation (Villa et al., 1996). Food contains a lots of carcinogens and co-carcinogens such as free radicals, N-nitrous compounds, secondary bile acids, polyamines, and heterocyclic amines (used in food processing) (Parkin et al., 1999). Co-carcinogens usually need activation in the gut. Their activation and inactivation is maintained by the gut flora, some phytochemicals and metabolites. Meat processing leads to elevated carcinogen production. Meat and fish cooking leads to formation of heterocyclic amines, especially at high temperatures or when exposed to direct fire. Our study shows that grilled, fried and egg-fried foods are associated with high CRP formation, and fried and egg-fried foods are risk factors for CRC as well. We consider preserved food as a risk factor for CRP and CRC, while marinated food is associated with CRP. Some observations propose that gut bacteria could transform bile acids into secondary bile acids (deoxycholic and litocholic) which possess high toxicity and stimulate large bowel mucosal proliferation (Burnstein, 1993). Food fatty acids also alter the composition and the quantity of bile acids. Accelerated bowel transit time could diminish exposition time of mucosa to food carcinogens, and enlarged volume could dilute them. Thus food fibers bind, inactivate and

Way of cooking — fried meat Cholecystectomy Fruit and vegetables

Polyamines Colorectal cancer Bioactive components

Tobacco smoking Fish

Vitt. A, B, C, D, folic acid, Selenium, Calcium

Risk dietary factors Risk non-dietary factors Protective factors

Contaminated water Gender Probiotics Fats Age Fibers Red meat Laxatives Flavonoids Sugar Helicobacter pylori Dairy products Alcohol Occupational risks Calcium Eggs Colorectal polyps Fluids

Way of cooking - high t° Radiotherapy Cereals

Table 6. Summary of all protective and risk factors tor CRC and CRP.

experimental animal studies and epidemiological studies (Ford, S. 1999).

**9.1.2 Food additives and contaminants** 

carry out the luminal carcinogens.

Way of cooking - grilled meat IBD, diabetes. mellitus,

Food additives and contaminants

(heterocyclic amines)

The first announcement of the relationship between high intake of fats and CRC dates from 1969 (Wynder et al., 1969). The relationship between saturated/animal fatty acids and CRC risk is tight. Saturated fats play a crucial role in the initiation, promotion and progression of CRC. Saturated fats increase the bile excretion, which is followed by toxic impact upon colon epithelium and hyperproliferation (Burnstein, 1993). The current study proved that consumption of fatty foods, bacon, and margarine is strongly associated with CRP and CRC development. The results of animal studies report that in the animals, which are on high fat diet, elevated cell proliferation and free radicals are observed. Inflammation and oxidative stress play a significant role in human carcinogenesis, besuse DNA lesions and chromosomal instability could occur (Evans et al., 2004; Kryston et al., 2011; Sedelnikova et al., 2010). On the other hand omega-3 polyunsaturated fatty acids decrease inflammation, inhibit formation and progression of preneoplastic colorectal lesions (Anti et al., 1994). The so-called "Mediterranean" diet, which is rich in fish and sea products, reduces the risk for colorectal cancer. Our study proves that regular consumption of fish and sea products (more than twice a week) strongly prevents CRP and CRC. Probably, the protective effect of omega-3 polyunsaturated fatty acids is due to stimulation of apoptotic program, decrease of inflammation, mucous prostaglandins and decrease of the secondary bile salts concentration, which are promoters for CRC. There are data that omega-3 polyunsaturated fatty acids modulate the action of COX-2 and induce the expression of 15 hydroxyprostaglandin dehydrogenase, a physiologic COX-2 antagonist (Lim et al., 2008).

### **9.1.4 Carbohydrates**

It is believed that decreased intake of carbohydrates reduces the risk for polyp formation (Lubin et al., 1997). Complex long-chained carbohydrates are considered highly protective in contrast to saccharose (World Cancer Research Fund and American Institute for Cancer Research, Food, Nutrition and the Prevention of Cancer: A Global Perspective., 1997). Some studies confirm that persistent hyperglicaemia and the subsequent insulin release are stimuli for hyperproliferation of colon epithelium and risk factors for the development of CRC (Calle & Thun, 2004). In contrast, other studies did not observe such an association (Weijenberg et al., 2008). Complex long-chained carbohydrates must supply 46-60% of all energy intake, while refined saccharose must supply <10% according to some recommendations (World Cancer Research Fund and American Institute for Cancer Research, Food, Nutrition and the Prevention of Cancer: A Global Perspective., 1997). The results of this study support the notion that saccharose and sweets are risk factors for CRP and CRC, while complex long-chained carbohydrates have protective effect.

#### **9.1.5 Red meat**

Consumption of red meat is connected with development of CRC (Ferrucci et al., 2009). Our study also confirmed the fact that regular consumption of red meat, large amounts of meat and meat products, preserved meat, ham, long- and short lasting sausages, pork, subproducts, and meat delicacy, is strongly associated with CRP, and CRC initiation and progression. On the other hand intake of fish, hare, lamb, white meat and poultry are highly protective. The possible pro-carcinogenic effect of red meat could be explained by the elevated heme iron content which could serve as a source for production of free radicals and

Risk and Protective Factors for Development of Colorectal Polyps and Cancer 189

The incidence of CRC is almost always higher in men (Parkin et al., 1999). Our data support these findings, as the men/women ratio was 1.2/1 in patients with CRP and 1.23/1 in patients with CRC. These differences could be explained with different life style, diet habits, physical activity, tobacco smoking, and consumption of alcohol, usage of NSAID and iron stores. There are and speculations about the protective role of female sex hormones (Crandall, 1999). Hormone replacement therapy in women is not recommended, because of the risk of vascular damages, thromboembolism and breast cancer (Scottish Intercollegiate Guidelines Network. Management of Colorectal cancer. A national clinical guideline, 2003).

The interacting reasons for neoplastic changes in the colon are clinically manifested as a CRC during the second half of life. The mean age of our patients with CRP is 60 years and the mean age of our patients with CRC is 64 year. The mortality rate is increasing in parallel

Frequent use of laxatives is among risk factors according to our data. This result is supported by some other studies (Van Gorkom et al., 1999). Probably, laxatives exert direct

The presumable mechanism of iron influence as a risk factor for CRC is connected with the formation of the free radicals from the unabsorbed iron, which damage colon epithelium. Heterozygotic patients who have not developed haemochromatosis are at elevated risk of developing CRC (Altes et al., 1999). The high risk of developing CRP and CRC in our patients who have regularly consumed red meat could be partially explained with the high

Our data show that exposure to petrol and metal is a risk factor for CRP and CRC. It is possible that petrol derivates and metals exert harmful effect upon colonic mucosa. Other exogenous risk factors are: use of anthranoid laxatives, working in petrol industry, production of synthetic materials, wood- and metal processing. Ionizing radiation increases the risk for CRC in radiation treatment of small pelvis after latent period of 15 years (Levin

Pathological gut flora could produce potential carcinogens, deconjugate bile acids and impair cell DNA molecule (Aries et al., 1969). Our study ascertained the fact that *H. pylori*  infection serves as a risk factor for CRC development. Similar results are reported from other authors (Zumkeller et al., 2006). However, more extensive studies are needed to prove

with advancing age according to reported data (Crandall, 1999).

amount of organic iron, which is available in the heme molecule.

**9.2.3 Gender** 

**9.2.4 Age** 

**9.2.5 Laxatives use** 

**9.2.7 Occupation** 

et al., 2002).

**9.2.8 Gut flora** 

toxic effect upon colon mucosa.

**9.2.6 Iron and haemochromatosis** 

mucosal hyperproliferation (Nelson, 2001). The results obtained by other studies deny the role of dietary Fe and iron status for CRC development (Tseng et al., 1997). N-nitrous compounds in the red meat and produced during the food processing with high temperature polycyclic carbohydrates and heterocyclic amines are also possible reasons for the harmful effect of red meat (De Meester & Gerber, 1995) Red meat consumption in elderly individuals should be limited to 70-80g/day.
