21: Cancer



Cancer is one of the leading causes of death worldwide, ranking first or second after cardiovascular disease, in most countries. Worldwide in 2020, it was estimated, that 19.3 million new cancer cases and 10 million cancer deaths occurred (Sung et al., 2021). Almost one‐quarter of total cancer cases as well as 19.6% and 14.2% of global cancer deaths were observed in Europe and America, respectively. Regarding cancer cases, female breast cancer was the most commonly diagnosed, while lung cancer was the leading cause of cancer death worldwide. Concerning gender, lung cancer was the most commonly diagnosed among men, while breast cancer was among women. The same was observed for cancer deaths (Sung et al., 2021).

These numbers are expected to rise, as 23.6 million new cancer cases will be diagnosed annually by 2040 due to aging and growth of the population (Jemal A et al., 2019). Therefore, optimal primary prevention and management actions should be taken to address this public health issue.


Cancer research has expanded in the last decades, increasing our understanding in the molecular pathways that lead to cancer development. Cancer development is associated with a disruption of molecular pathways and the function of specific genes that control normal cell proliferation, growth, and apoptosis through genetic and epigenetic changes. Despite the fact that there are numerous relevant molecular events, the main characteristics of most cancers are known as the “hallmarks of cancer” and are summarized in the 2018 expert report of the World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) (Figure 21.1) (WCRF/AICR, 2018).

The process of cancer development typically lasts many years. During these years, lots of different environmental factors, including diet and physical activity may interact with host factors and, as a consequence, can protect from or increase the susceptibility to cancer development (Figure 21.2) (WCRF/AICR, 2018).

Our first knowledge of the effects of environmental exposures on the risk of developing cancer dates back to the 1960s, when individuals, who moved from countries with low risk of some cancers to high risk countries were reported to have an increase in cancer rates at equal levels, or even higher, compared to the host population (Shimizu H. et al., 1987). Since then, there is abundant evidence, mainly from observational studies that have shown the importance of environmental factors, which account for 90% to 95% of cancer cases, while the remaining 5% to 10% are due to genes (Anand et al., 2008).

Schematic illustration of hallmarks of cancer and two enabling characteristics.

FIGURE 21.1 Hallmarks of cancer and two enabling characteristics.

Source: (WCRF/AICR, 2018).

According to the WHO, between 30% and 50% of all cancer cases worldwide are estimated to be prevented though lower exposure to tobacco, infectious agents, and occupational carcinogens as well as through alterations in lifestyle factors, such as adherence to a healthy diet, preventing or managing overweight or obesity, and engaging with physical activity (WHO, 2019). Considering current estimates about lifestyle, diet is attributable to 20% to 25% of cancer burden. This range seems to include a 10% to 15%, which encompasses excess body weight and physical inactivity, approximately 5% is attributed to alcohol and the remaining 5% to dietary factors (Giovannucci, 2018). Therefore, understanding the magnitude of these factors is of major importance to potentially prevent several cancer cases through lifestyle modifications.


Overweight and obesity are collectively characterized by abnormal, and excess, fat accumulation associated with the incidence of several different disease entities. Data by the WHO have shown that 1.9 billion adults and 340 million children and adolescents were living with excess body weight in 2016, and it is estimated that these numbers will be increased (WHO, 2020).

Schematic illustration of diet, nutrition, physical activity, other environmental exposures, and host factors interact to affect the cancer process.

FIGURE 21.2 Diet, nutrition, physical activity, other environmental exposures, and host factors interact to affect the cancer process.

Source: (WCRF/AICR, 2018).

Worldwide, considering lifestyle factors, obesity is ranked as the second leading preventable cause after smoking and, in general, is considered the third risk factor for cancer incidence after smoking and infections. Should obesity trends continue to rise over the next years, it is projected to lead, in the USA, to at least 500,000 additional cases annually and will be the leading modifiable risk factor of cancer, exceeding smoking. At a global level, approximately 3.9% of all types of cancers in 2012 were attributable to overweight and obesity levels in 2002 (Arnold et al., 2015), with the proportions across countries varying widely, ranging from 0.4% to 8.2%.

There is consistent data over the last several decades that support the association between overweight, obesity, and cancer risk. The 2018 WCRF/AICR expert report concluded that being overweight or obesity in adulthood increases the risk of some types of cancers, including colorectum, post‐menopausal breast, kidney, endometrium, adenocarcinoma of esophagus, liver, pancreas, advanced prostate, gastric cardia, oral, oropharyngeal, and larynx, while weight gain in adults is strongly associated with a high risk of post‐menopausal cancer (WCRF/AICR, 2018).

Endometrial cancer has one of the strongest associations with obesity, with each 5 kg/m2 increase in body‐mass index (BMI) related to a 54% higher risk of cancer (D. Aune et al., 2015). Moreover, the International Agency for Research on Cancer (IARC) Handbook reported evidence that excess body weight is further associated with a high risk of thyroid cancer, meningioma, and multiple myeloma (Lauby‐Secretan et al., 2016). On the other hand, it seems that being overweight or obesity in young adulthood (i.e.,18–30 years) protects against both pro‐ and post‐menopausal breast cancer, although the higher risk of post‐menopausal breast cancer later in life outweighs any potential benefit (WCRF/AICR, 2018).

Given the burden of overweight and obesity, there were interesting data from recent observational studies regarding weight management and the risk of developing cancer. A pooled analysis of prospective studies with regard to diet and cancer (Teras et al., 2020) including approximately 180,000 women aged ≥50 years, reported that women who sustained weight loss (more than 2 kg between baseline and the first follow up, that was not regained after a 10‐year final follow up) had a lower risk of breast cancer compared with women whose weight was stable. In general, this study demonstrated that the greater the weight loss, the lower the risk of breast cancer. In the same context, the UK women’s cohort study (Moy et al., 2018) concluded that women who lost weight had a lower risk of post‐menopausal breast cancer compared to women who gained weight or had a stable weight. Moreover, the women’s health initiative study demonstrated lower risks of both endometrial and breast cancers’ incidence in women with weight loss compared with those whose weight remained stable (Chlebowski et al., 2019; Luo et al., 2017).

Moreover, data from the Look AHEAD trial demonstrated, that individuals with overweight or obesity and type 2 diabetes, who successfully achieved weight loss by reducing energy intake and increasing physical activity, had a 16% lower risk of cancers related to obesity (Yeh et al., 2020). There are, also, few data regarding the beneficial effects of bariatric surgery in cancer risk. According to a 2019 systematic review and meta‐analysis of eight population‐based cohort studies that included 635,642 patients (114,020 patients who have undergone bariatric surgery and 521,622 controls), bariatric surgery was significantly associated with a 45% lower incidence of obesity‐associated tumor types (Wiggins et al., 2019).

Multiple mechanisms have been proposed to explain the link between excess body weight and cancer incidence (Figure 21.3). In obesity, hypoxia of the adipose tissue contributes to a chronic low grade inflammatory state, which leads to changes in its structural and functional damage, such as abnormal adipokines secretion, e.g., adiponectin and leptin. Increased leptin levels, as observed in obesity, have been shown to trigger tumor initiation and further metastasis in several types of cancer, including liver, lung, breast, colorectal, kidney, and prostate cancers (Ghasemi et al., 2019; Sánchez‐Jiménez et al., 2019).

Furthermore, hyperinsulinemia, insulin resistance, and abnormalities in the insulin‐like growth factor‐1 (IGF‐1) axis have been proposed as important mechanisms. Insulin can promote carcinogenesis through direct and indirect stimulation of cells. It can increase the circulation levels of the IGF‐1 through a reduction in the circulating levels of its binding proteins. IGF‐1 and insulin can activate mechanisms related to proliferation, angiogenesis, and inhibition of apoptosis, all of which are associated with tumorigenesis (Hopkins et al., 2020; Jiramongkol & Lam, 2020). It is well‐established that both insulin resistance and hyperinsulinemia are common in obesity, and as a result they can increase cancer risk in obese individuals.

Schematic illustration of proposed mechanisms for the association between body fatness and cancer progression.

FIGURE 21.3 Proposed mechanisms for the association between body fatness and cancer progression. IGF‐1 = insulin growth factor‐1; IGFBP1 & 3 = insulin growth factor binding proteins‐1 & 3.

Source: (Wilson et al., 2022).

Finally, in the context of obesity, higher levels of estrogens are observed due to the higher activity of the enzyme aromatase in adipose tissue. Consequently, higher conversion rates of androgens to estradiol are observed. Elevated levels of estrogens can promote carcinogenesis and have been shown to increase breast cancer risk (Fortner et al., 2016) as well as endometrial cancer (Shaw et al., 2016).


Alcoholic beverages have been classified as carcinogenic to humans since 1988 (IARC, 1988). Only in 2012 was it estimated that 5.5% of new cancer cases was attributed to alcohol consumption (Praud et al., 2016). Recently, both the updated IARC monographs and the 2018 WCRF/AIRC report concluded that there is sufficient evidence that alcohol consumption increases the risk of several types of cancer, including cancers of upper aerodigestive tract, e.g., mouth, larynx, pharynx, esophagus (squamous cell carcinoma), and cancers of the liver, colorectum, stomach, and female breast (WCRF/AICR, 2018; Wild CP, 2020). According to the 2018 WCRF/AIRC report, there is probable evidence that alcoholic drinks consumption is associated with a higher risk of cancers of the pancreas, lung, and skin (basal cell carcinoma and malignant melanoma), although, this relationship may be confounded by other lifestyle factors, such as smoking. On the other hand, the same report concluded that there is probable evidence showing an inverse association between moderate alcohol consumption (up to 2 alcoholic drinks per day) and risk of kidney cancer (WCRF/AICR, 2018).

Both the amount of alcohol consumed and the type of cancer may affect the magnitude of the increase of cancer risk. The greater risks are observed in heavy (namely ≥3 drinks per day or ≥8 drinks per week for women; ≥4 drinks per day or ≥15 drinks per week for men) and moderate (defined as ≤1 drink per day for women and ≤2 drinks per day for men) alcohol consumption categories (LoConte et al., 2018). However, the risk for some types of cancer is present even at low levels of consumption, as reported in a meta‐analysis of observational studies of approximately 92,000 light drinkers (up to 1 drink/d), in which drinking no more than one alcoholic beverage per day was associated with a higher risk of oropharyngeal cancer, female breast cancer, and esophageal cancer (squamous cell carcinoma) (Bagnardi et al., 2013).

Alcohol contains a plethora of substances. Some of them, such as resveratrol, a phytochemical found in red wine, have been shown in laboratory studies to associate with anticarcinogenic properties (Dybkowska E. et al., 2018). However, human studies have not reported benefits from drinking red wine regarding cancer prevention. The 2018 WCRF/AIRC report concluded that the devastating effects of alcoholic beverages in cancer risk have been observed consistently, regardless of the type of alcoholic drink.

There is an emerging body of research showing that despite the presence of several carcinogenic compounds, the major cause of the relationship between alcohol consumption and cancer development is ethanol. Its metabolite, acetaldehyde, is characterized as human carcinogen that can rapidly bind to DNA and cause mutations (Liu et al., 2015). Furthermore, through its metabolism, reactive oxygen species are generated and as a consequence, DNA damage is observed. Moreover, it is considered that ethanol can act as a solvent that enhances the penetration of carcinogenic compounds into cells. People exposed to the concurrent use of alcohol and tobacco have higher risks of cancers of the respiratory tract and upper digestive area. A further mechanism that may explain the higher risk of breast cancer and hormone sensitive cancers in general, is the increase of estrogen circulating levels and the higher proliferation of estrogen receptors (Liu et al., 2015).


Unprocessed meat, such as beef, lamp, pork, mutton, goat, and veal meat are referred to as red meat. The term “processed meat” includes meat that has been processed through smoking, curing, salting, and fermentation as well as procedures used to preserve foods or enhance flavor. This can include bacon, ham, salami, and sausages, except for fresh sausages that may not always be included as processed meat (Bouvard et al., 2015).

In 2015, IARC experts reported that processed meat was classified as a Group 1 carcinogen (strong evidence that it causes cancer), whereas red meat as a Group 2A carcinogen (it probably causes cancer), based on sufficient data with regard to colorectal cancer (IARC, 2015). A meta‐analysis published in 2011 included 10 cohort studies and concluded that there was a significant 17% increased risk of colorectal cancer per 100 g/d of red meat, and an 18% increased risk per 50 g/d of processed red meat (Chan et al., 2011). Similarly, the 2018 WCRF/AICR report demonstrated that there is strong evidence that processed meat “convincingly” increases colorectal cancer incidence, whereas red meat is “probably” associated with an increased risk of colorectal cancer. The analysis of the available data reported that per 100 g/d of red meat, the risk of colorectal cancer increases by 12%, whereas per 50 g/d of processed red meat, it increases by 16% (WCRF/AICR, 2018). Notably, except for colorectal cancer, there is growing, but still limited evidence that a higher consumption of red and processed meat may be associated with an increased risk of other types of cancer, such as stomach, prostate and breast cancers (IARC, 2015; Inoue‐Choi et al., 2016; Wu et al., 2016). In a systematic review and meta‐analysis of 148 prospective studies, the high intake of total red and processed meat further increased the risk of lung and renal cancers by approximately 20% and 19%, respectively (Farvid et al., 2021).

Schematic illustration of proposed mechanisms linking processed and red meat to colorectal cancer development.

FIGURE 21.4 Proposed mechanisms linking processed and red meat to colorectal cancer development. PAHs = polycyclic aromatic hydrocarbons; HAAs = heterocyclic aromatic amines.

Source: (Turesky, 2018 / with permission of Swiss Chemical Society).

There is mounting evidence for the potential biological mechanisms that explain these associations (Figure 21.4). Processing meat, for example during smoking and curing, produces several carcinogens, including polycyclic aromatic hydrocarbons and N‐nitroso compounds, while cooking meat at high temperature, such as grilling or barbecuing, leads further to the formation of heterocyclic amines. Besides, it is suggested that the heme iron, which is present at high levels in red and processed meat, can promote carcinogenesis through lipid peroxidation and the formation of DNA adducts and N‐nitroso compounds (Joosen et al., 2009; Sinha et al., 1998).


Dietary fiber, which could be defined briefly as the constituents of the plant walls that are not digested in the small intestine, is found mainly in plant foods, such as whole‐grain products, fruits, vegetables, nuts, seeds, and legumes. Their intake is considered probably related to a reduced risk of colorectal cancer, with an increase of 10 g/d of dietary fiber associated with a 9% reduced risk of colorectal cancer (WCRF/AICR, 2018).

Their intake through the consumption of whole plant foods has been also associated with a reduced likelihood of gaining weight and overweight or obesity, which results in a lower risk of obesity‐related types of cancers (WCRF/AICR, 2018). Dietary fiber reduces gastrointestinal transit time, dilutes carcinogens in the colon, and reduces their absorption and contact with the epithelial cells. Furthermore, fiber promotes the avoidance of gut microbial dysbiosis as well as the fermentation of intestinal bacteria and the increase of production of short‐chain fatty acids, like butyrate, which has been shown to inhibit cell proliferation and promote apoptosis (Baena & Salinas, 2015; de Vries, 2015; Romaneiro & Parekh, 2012).

Whole grains, according to the American Association of Cereal Chemists (AACC), are defined as consisting of the “intact, ground, cracked, or flaked caryopsis, whose principal anatomical components, including the starchy endosperm, germ, and bran are present in the same relative proportions as they exist in the intact caryopsis” (AACC, 2000). Retaining the original kernel makes whole grains rich in several substances and dietary factors, such as vitamins, dietary fibers, and phytochemicals and is one of the reasons why their consumption has been consistently associated with lower cancer risk, with the strongest evidence for colorectal, pancreatic, gastric, and esophageal cancers based on a systematic review of meta‐analyses of observational studies (Gaesser, 2020). The 2018 WCRF/AIRC report states that the consumption of whole grains is strongly associated with a lower risk only of colorectal cancer. Each 90 g/d increase in the consumption of whole grains has been reported to reduce the risk of colorectal cancer by 17% (WCRF/AICR, 2018). In the same context, in a meta‐analysis of nine prospective studies, the risk of colorectal cancer was reduced by 5% for each 30 g/d increase in intake (Schwingshackl et al., 2018).

Nutrients, substances, and bioactive compounds of whole grains have been demonstrated to have potential anticarcinogenic properties, reduce oxidative stress, and ameliorate levels of insulin and proinflammatory cytokines (Fardet, 2010; Slavin, 2003; Song et al., 2015). In addition, whole‐grain intake is associated with lower excess body weight and as a result they could have a beneficial role in lowering the risk of adiposity‐related type of cancers (Harland & Garton, 2008).

Considering fruits and vegetables, older studies demonstrated strong and convincing evidence between their consumption and reduced cancer risk. However, the results of long‐term studies in the last decade weaken this association. Therefore, the 2018 WCRF/AIRC report concluded that the greater consumption of whole fruits and/or non‐starchy vegetables was “probably” associated with a lower incidence of aerodigestive cancers, such as mouth, pharynx, larynx, nasopharynx, and esophagus as well as stomach and lung cancers (WCRF/AICR, 2018). There are, also, some promising results on specific‐tumor subtypes, as demonstrated in a systematic review and meta‐analysis of prospective studies published in 2021, in which total fruits and vegetables consumption was associated with a 9% lower overall breast cancer risk, but also with 11% and 26% lower risk of estrogen‐receptor and progesterone‐receptor positive and negative breast cancer, respectively (Farvid, Barnett, et al., 2021).

As plant‐based foods, fruits and vegetables contain numerous nutrients and bioactive compounds that have been reported to protect against cancer development. Furthermore, they are low energy‐dense foods, high in dietary fiber, and their consumption has been shown to likely increase satiety and reduce the likelihood of weight gain, overweight, and obesity (WCRF/AICR, 2018).

Although the intake of whole grains, vegetables, and legumes seems to be beneficial, it should be noted that there are some factors to be considered. For example, grains and legumes can be contaminated by aflatoxins, that are produced by some molds, and it is observed mainly in low and middle income countries (Wild et al., 2020). Aflatoxin is classified as carcinogenic to humans according to the IARC and has been shown to strongly increase the incidence of liver cancer (WCRF/AICR, 2018; Wild et al., 2020). Except for aflatoxin, the positive effects of the consumption of these plant foods may be disrupted by the consumption of preserved non‐starchy vegetables. The 2018 WCRF/AIRC report demonstrated, that higher intake of foods preserved by salting, including preserved vegetables, such as those, which are pickled or salted can probably increase the risk of developing stomach cancer (WCRF/AICR, 2018). Hence, given these results, individuals should be aware of the safety and quality of the plant foods they consume to be protected against cancer.


The association between dairy products, calcium and cancer risk is complicated, because there are several data indicating reduced risk of some cancers and increased risk of others. Indeed, the 2018 WCRF/AICR report supports an inverse association between intake of dairy and the risk of colorectal cancer risk (WCRF/AICR, 2018). Regarding dairy consumption, for each 400 g the risk was reduced by approximately 13%. Moreover, it reported that diets high in calcium may reduce breast cancer risk, although the evidence is considered as limited/suggestive. On the other hand, there is limited evidence that diets high in dairy products and calcium may increase the risk of prostate cancer. For each 400 g of dairy consumption, prostate cancer risk was estimated to increase by 7%. However, it should be noted that the more pronounced positive associations with calcium are observed in higher intakes (approximately more than 1500 mg per day) compared to the Recommended Dietary Allowance (1000–1200 mg) and even higher doses (> 2000 mg) has been associated with advanced prostate cancer (Aune et al., 2015; Wilson et al., 2015).

Dairy products may lead to a reduced risk of colorectal cancer mainly due to their calcium concentration. The main mechanisms include the binding of calcium to the potentially toxic free fatty acids and secondary bile acids, the preservation of integrity of epithelial cells and the reduction of intestinal inflammation (Norat & Riboli, 2003; Song et al., 2015). In contrast, considering prostate cancer, the principal mechanism involves the increase in IGF‐1 levels, although it is not completely understood. There is some evidence demonstrating that milk intake may increase IGF‐1 levels and as a consequence the risk of prostate cancer (Harrison et al., 2017). The other suggested mechanism includes the downregulation of the 1,25‐dihydroxyvitamin D formation, which is the active form of vitamin D (Abu el Maaty & Wölfl, 2017). In this regard, cellular proliferation in the prostate is increased.


Both sugar‐sweetened drinks, which include liquids with added sugars, such as sodas, energy, and sports drinks, as well as fast foods tend to be high energy‐dense and have a low impact on satiety. Their consumption has been associated with higher risk of long‐term weight gain, overweight and obesity, and as a consequence indirectly may be a cause of cancer development (WCRF/AICR, 2018). However, data from PREDIMED study demonstrated a significant positive association between simple sugars in liquid form and cancer risk, regardless of BMI and energy intake, which should be further researched in the future (Laguna et al., 2021). Moreover, there are interesting data from the Nutrinet‐Santé prospective cohort study (approximately 105,000 adults were assessed) with regard to ultra‐processed foods (e.g., cookies, cakes, soft drinks, salty snacks) demonstrating that a 10% increase in the intake of those foods has been associated with a 12% greater risk in overall cancer risk (Fiolet et al., 2018).


Examining the effects of single nutrients or food groups in cancer risk is a proposed reason why some relevant studies have failed to show consistent results. Therefore, in the last several decades there is a shift in nutrition research to more holistic dietary patterns, which can take into consideration all the interactions between food components. To this context, there is some data demonstrating that a priori dietary patterns and numerous dietary indices have been associated with either reduced or higher risk of various cancer types. The strongest evidence has been shown with regard to colorectal and breast cancer, with the healthy eating index (HEI‐2005 or HEI‐2010), Mediterranean diet score and dietary approaches to stop hypertension (DASH) associated with a reduced risk (Steck & Murphy, 2020). Furthermore, there are numerous prospective and case‐control studies that have assessed the effects of a posteriori dietary patterns in cancer incidence. Two main patterns were found, including “healthy” or “prudent” and “unhealthy” or “Western” patterns. The former has been associated with a lower risk of colorectal, breast, and lung cancers and the latter has been consistently related to an increased risk of colorectal cancer, while there are inconsistent results regarding breast, pancreatic, and prostate cancers. Hence, case‐control studies have reported a positive association while prospective studies have demonstrated no consistent results (Steck & Murphy, 2020). Considering single nutrients and foods, healthy patterns include mainly fruits and vegetables, whole grains, legumes, nuts/seeds, fish, and poly‐unsaturated fats, while they are characterized by low amounts of red and processed meat, added sugars, saturated and trans fats. On the other hand, unhealthy patterns are characterized by the opposite features (Grosso et al., 2017).

Notably, while the evidence regarding the direct association of Mediterranean diet (MD) and Western diet with lower and higher cancer risk, respectively, is inconclusive, the 2018 WCRF/AIRC report suggest that MD is “convincingly” associated with a reduced risk of weight gain, overweight, or obesity. On the other hand, a Western dietary pattern is “probably” associated with an increased risk of being overweight or obese. Therefore, these patterns may, also, indirectly have a huge impact on cancer development. Furthermore, the same report concluded that diets with high glycemic load are “probably” associated with a higher risk of endometrial cancer, with one unit increment to be related with a 15% higher risk. Considering the relevant mechanisms, a diet higher in glycemic load can increase the postprandial glucose and insulin levels in the short‐term, while in the long‐term it may be associated with a higher risk of obesity and diabetes, which may further increase the risk of endometrial cancer (WCRF/AICR, 2018).


Although there is evidence that a high intake of plant‐based foods, including fruits and vegetables may lower the cancer risk, the evidence regarding the use of vitamin supplements for cancer prevention is limited. Notably, despite the limited evidence in terms of higher plasma levels of vitamin D and lower colorectal cancer risk, the results of its supplementation are inconsistent (Dimitrakopoulou et al., 2017; Manson et al., 2019; WCRF/AICR, 2018). Consequently, to date, there is no recommendation to assess vitamin D levels and provide supplementation, in case of deficiency, to prevent cancer incidence. Furthermore, there is strong evidence that high‐doses of beta carotene can “convincingly” increase the risk of lung cancer in individuals who smoke or used to smoke as well as that high‐doses of vitamin E may increase prostate cancer incidence (WCRF/AICR, 2018). For these reasons, no dietary supplement is recommended for cancer prevention, instead individuals should obtain nutrients and these compounds from foods that provide the potential for synergistic effects against cancer (Rock et al., 2020; WCRF/AICR, 2018).


Sedentary behavior is defined as “any waking behavior that characterized by an energy expenditure less than or equal to 1.5 Metabolic Equivalents of Task (METs) while in a sitting or reclining posture” (Sedentary Behaviour Research Network, 2012). In the last several decades, sedentary behavior has been evaluated with regard to cancer risk and now it seems to be a further important modifiable risk factor, especially given that some data demonstrate that physical inactivity is attributable to approximately 2.9% of all cancer cases in the United States (Islami et al., 2018).

In a meta‐analysis that includes 14 observational studies, a 24% higher risk of cancer has been shown when high levels of time were spent sitting compared to low, after adjusting for physical activity (Biswas et al., 2015). Considering the types of cancer, the strongest evidence has been demonstrated for colon, breast, and endometrial cancers. In a meta‐analysis of 43 observational studies, each increase of 2 h/d sitting time was associated with 8% and 10% greater risk of colon and endometrial cancer, respectively (Schmid & Leitzmann, 2014).

The 2018 WCRF/AIRC report concluded that sedentary behavior increases the risk only of endometrial cancer and graded the evidence as “limited‐suggestive” (WCRF/AICR, 2018). The 2018 physical activity guidelines advisory committee (PAGAC) report demonstrated that there is moderate evidence for a significant association between increased levels of sedentary behavior and a greater risk of colon, endometrial, and lung cancer (PAGAC, 2018).

The relevant mechanisms are not fully understood. Although, there are inconsistent data, sedentary behavior may increase the risk of weight gain, overweight, or obesity that may lead to cancer development.


Research about physical activity and cancer has emerged in the past decade and, to date, evidence was derived mainly from multiple observational epidemiological studies showing that higher levels of physical activity are consistently associated with a lower risk of several cancers. Almost all the available data in the literature focused on aerobic physical activity, and they are summarized and evaluated by the 2018 PAGAC and 2018 WCRF/AIRC expert reports (PAGAC, 2018; WCRF/AICR, 2018). After thorough evaluation, they concluded that there is some evidence demonstrating a reduced risk of 13 types of cancer, when comparing the individuals in the highest category of physical activity to those in the lowest. More specifically, the PAGAC concluded that there is strong evidence that being physically active reduces the risk of breast, bladder, endometrial, colon, esophageal adenocarcinoma, gastric cardia, and renal cancers. It is also demonstrated moderate evidence for lung cancer, although smoking may be an important confounder, and limited for hematologic, ovary, head and neck, pancreas and prostate cancers (PAGAC, 2018). Given the different criteria for grading, the 2018 WCRF/AICR report found strong evidence regarding a “convincing” association between physical activity and a reduced risk of colon cancer as well as a “probable” association with a lower risk of endometrial and post‐menopausal breast cancers. In a meta‐analysis of the available cohort studies published by WCRF/AICR, researchers found that when comparing the highest levels of total physical activity with the lowest, risk was reduced by 20% and 13% in colon cancer and post‐menopausal breast cancer, respectively (WCRF/AICR, 2018). Moreover, in the same report, the association between physical activity and decreased risk of esophagus, liver, post‐menopausal breast, and lung cancers was graded as “limited”. In 2019, the American College of Sports Medicine (ACSM) published an expert review demonstrating similar conclusions compared with the 2018 PAGAC report, except for an additional protective role of physical activity against liver cancer incidence. The magnitude of the reductions in relative risks for most cancer types ranges from approximately 10% to 20% (Patel et al., 2019).

Schematic illustration of mechanisms linking physical activity to decreased cancer risk.

FIGURE 21.5 Mechanisms linking physical activity to decreased cancer risk.

Source: (McTiernan, 2008).

Furthermore, regarding the intensity and the type of physical activity, and given the different methods reported in the literature for measuring its levels, it is difficult to determine the precise levels and type of exercise training that can reduce the risk of most cancer types. However, in this context, and according to the 2018 WCRF/AICR report, there is strong evidence that vigorous (>6 METs or >60% of peak heart rate) physical activity is “probably” associated with 21% and 10% lower risk of premenopausal and post‐menopausal breast cancer risk, respectively, when comparing the highest and lowest levels (WCRF/AICR, 2018).

An emerging body of research suggests a variety of mechanisms though which physical activity can have a beneficial role in developing cancer (Figure 21.5). Exercise training may have direct effects on minimizing chronic inflammation and improving function of the immune system. Moreover, it may indirectly prevent weight gain as well as being overweight or obese through the management of body weight and the maintenance of healthy body fat levels. It may, also, be associated with the reduction of bioavailable sex‐hormones levels, the improvement of insulin sensitivity, and the consequent reduction of insulin levels. Furthermore, considering the risk of colon cancer, exercise may lead to a decreasing transit time and, as a result, a reduced exposure of intestinal epithelial cells to carcinogens (Hojman et al., 2018).


Regarding diet, nutrition, and cancer prevention, the available recommendations are the updated 2018 WCRF/AIRC recommendations and the 2020 American Cancer Society (ACS) guidelines on nutrition and physical activity (Tables 21.1 and 21.2, respectively). Briefly, they promote a body weight within the healthy range and a healthy dietary pattern rich in vegetables, fruits, whole grains, and beans, while suggesting the limitation of red and processed meat, sugar‐sweetened drinks, processed foods, fast foods, and refined grains consumption. They also recommend against the use of supplements for cancer prevention. Furthermore, regarding alcohol consumption, both recommend individuals limit their consumption to national guidelines (e.g., in the United States: 1 drink per day for women, 2 drinks for men), although the WCRF/AIRC suggests even to avoid drinking. Moreover, the 2018 WCRF/AIRC recommendations suggest specific quantities of some foods and nutrients, as at least 30 g/d of fiber and 400 g/d of non‐starchy vegetables and fruits as well as consumption of red meat with no more than three portions (350–500 g) per week (Rock et al., 2020; WCRF/AICR, 2018).

Table 21.1 The 2018 WCRF/AICR recommendations for cancer prevention. AICR = American Institute for Cancer Research; BMI = body‐mass index; WCRF = World Cancer Research Fund; WHO = World Health Organization.

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Oct 25, 2023 | Posted by in CARDIOLOGY | Comments Off on 21: Cancer

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Recommendations Details Goals
Be a healthy weight Keep your weight within the healthy range and avoid weight gain in adult life.

  • Ensure that body weight during childhood and adolescence projects toward the lower end of the healthy adult BMI range.
  • Keep your weight as low as you can within the healthy range throughout life.
  • Avoid weight gain (measured as body weight or waist circumference) throughout adulthood.
Be physically active Be physically active as part of everyday life and life—walk more and sit less.

  • Be at least moderately physically active and follow or exceed national guidelines.
  • Limit sedentary habits.
Eat a diet rich in wholegrains, vegetables, fruit, and beans Make wholegrains, vegetables, fruit, and pulses (legumes) such as beans and lentils a major part of your usual diet.