*2.1.1 Mechanism*

*Multidisciplinary Approach for Colorectal Cancer*

and populations sampled [6].

**2. Diet**

**2.1 Dietary fiber**

are displaying rapid increases in the prevalence of cancers that are already more widespread in high-income countries [2]. Hence, CRC incidence and mortality rates are still rapidly increasing in many low-income and middle-income countries, while stabilizing or decreasing trends are being observed in highly developed countries where rates remain among the highest in the world [2]. As patterns and trends in CRC incidence and mortality are related to development levels, their incremental changes could be indicative of the adoption of a more Westernized lifestyle [2]. Targeted interventions tailored to available resources, including primary prevention, are necessary to decrease the global prevalence of CRC [2], as primary prevention dietary habits and other healthy lifestyle factors such as physical activity (PA) are viewed as the most effective and affordable strategy for curbing this global epidemic [3, 4]. In addition, genetic predisposition and environmental factors including diet and PA are considered to be the two main causes of CRC [3, 5].

Due to observed inconsistencies when appraising the effectivity of dietary and lifestyle-cancer relationships, this chapter will provide an overview of the current body of evidence regarding the role of diet, individual foods, alcoholic beverages, vitamins, body fatness, physical activity, and dietary supplements in terms of their classification as preventative or causative in the development of CRC. In addition, the strength of scientific evidence will be alluded to, as well as the modulating pathways responsible for reaping protective benefits or promoting carcinogenesis. Inconsistent findings across scientific literature related to dietary prevention of CRC include but are not limited to discrepancies in study design, dietary interventions assessed, baseline eating patterns,

Dietary fiber refers to carbohydrate polymers of plant origin that may or may not be associated to plant lignin [7]. There is convincing evidence that consuming wholegrains and foods containing dietary fiber decrease the risk of developing CRC [8]. A meta-analysis of prospective studies noted a 10% reduction in CRC risk for every 10 g of total dietary fiber consumed on a daily basis [9]. An analysis of specific sources of dietary fiber found that cereal fiber was associated with a dosedependent reduction in risk of 10% for every 10 g consumed; however, fruit fibers, vegetable fibers, and legume fibers were not associated with a significant reduction in risk. A meta-analysis of case-control studies and cohort studies on dietary fiber

intake and the incidence of CRC adenoma reported similar findings [10].

limited by dietary intake assessment conducted at baseline [12].

The European Prospective Investigation into Cancer and Nutrition (EPIC) supports the protective effect of dietary fiber, as the consumption of cereal fiber was significantly and inversely associated with colorectal cancer, colon cancer, and rectal cancer [11]. A significant inverse association was also noted between colon cancer and combined fruit and vegetable fiber intake, although the study was

The HELGA prospective study agrees with previous studies, as a 26% reduction in colon cancer risk in men was reported for every 10 g of dietary fiber consumed on a daily basis. However, the association was not significant in women, thereby suggesting that dietary fiber may be protective against CRC, but other factors such as phytochemicals, energy intake, body weight, and genetics may be equally influential, as is general dietary pattern [13]. This finding serves to demonstrate that consuming dietary fiber from a variety of sources (cereals, fruits, and vegetables)

**10**

Dietary fiber found in wholegrains may protect against the development of CRC by increasing fecal bulk through binding water and decreasing colonic transit time, thereby reducing the potential for fecal mutagens to interact with the colon mucosa, lowering the concentration of potential carcinogens, and exposing the colon mucosa to potential carcinogens for shorter period of time [4, 12, 14–17]. In addition, dietary fiber is fermented by intestinal microbiota into short-chain fatty acids (SCFAs) such as butyrate, which in experimental studies was shown to have antiproliferative and pro-apoptosis properties [4, 14–18]. SCFAs also lower fecal pH in the colon, thus providing a healthy intestinal environment [18], as well as inhibit chronic inflammation and cancer cell migration/invasion in the colon. However, these activities are only effective within certain physiological concentration ranges of SCFAs [18].

Other mechanisms include a reduction in secondary bile acid production [14], as well as enhancing the health of colonocytes [12] by modifying the composition of gut microbiota that can enhance immunity [18]. High-fiber diets may also reduce insulin resistance, a risk factor for CRC [7, 8, 14–16], by decreasing insulin growth factor (IGF)-1 activity, decreasing systemic inflammation via the production of SCFAs, and enhancing levels of colonic microbiota, thereby strengthening the intestinal barrier [4, 15, 16]. The anticarcinogenic properties of wholegrains also include being a source of antioxidants such as vitamin E, selenium, copper, zinc, and phytochemicals, as well as decreasing body adiposity [4, 14]. Wholegrains are also sources of lignans, phytoestrogens, and phenolic compounds [14], with many of these bioactive compounds being largely found in the bran and germ of the grain. To illustrate the plausible anticarcinogenic properties of several phenolic acids, experimental studies have showcased their ability to stimulate anti-oxidative activity [19].
