Nutrition-related factors play a complex role in the etiopathogenesis of human cancers. It is estimated that nutrition (diet), physical inactivity and obesity are responsible for the development of at least 35% of human cancers. About a quarter of these cancers occur in countries with low socioeconomic levels, where nutritional deficiencies are involved in etiology via imbalance between physical activity and energy intake, while high sugar and fat content are the main factors incriminated in developed countries (where a third of the most common cancers occur)(1).
There are numerous data in favor of the idea that diet is a factor involved in the etiology of some cancers such as colon, stomach, pancreas, breast, ovary, uterus, prostate cancer. Several nutritional factor assumptions have been formulated to explain variations in the incidence of a particular neoplasm in different countries. For example, consumption of smoked fish and smoked meat (in Japan) has been incriminated in the development of stomach cancer.
Nutritional factors are estimated to contribute to about 40% of all cancers in Western European countries, and even to 60% of women’s cancers in countries with increased incidence of breast cancers(2).
Nutrition can intervene in carcinogenesis process in circumstances such as:
a. Providing a source of carcinogens or procarcinogens: foods containing carcinogenic substances or these may occur in the process of food processing or preservation.
b. Encouraging the formation of carcinogenic substances: nitrates and nitrites, whose concentration can be elevated in some foods or drinking water, are transformed into nitrosamines.
c. Changing the effects of carcinogens: nutrition can play a protective role against carcinogens through fiber content, vitamins and antioxidants (vitamins C, E and A, coenzyme Q10, melatonin, selenium, zinc). Selenium and vitamin E reduce the risk of prostate cancer.
d. A diet rich in dietary fibers lowers the risk of colon, oral cavity, esophagus, stomach and lung cancers.
e. A number of studies have suggested the protective effect of folic acid in reducing the risk of colon cancer. This effect can be explained by two theories: (1) the synthesis of radicals, donors of methyl groups mediated by folate with methylation of DNA and regulation of gene expression; (2) there is a conversion of uracil to thiamine facilitated by folate, a mechanism involved in DNA repair(3).
Epidemiological data suggest that increased consumption of fat, protein, salt and a diet with low dietary fibers content (USA, Western Europe) are associated with an increased risk of colon cancer. The incidence of breast cancer is also high in countries where there is an increased consumption of saturated fats (USA, Scandinavia). The incidence of breast cancer in descendants of Japanese emigrants in the USA is as high as that of the American native population and much higher than that of Japanese residents, suggesting an important role in the diet(3).
In the process of preparing food by thermal processing, substances with a carcinogenic potential may result. Thus, benzopyrene and other aromatic polycyclic hydrocarbons may result from the process of thermal processing (pyrolysis) of foods, for example, when the meat is roasted or smoked. Vegetables such as celery, endive, cabbage, spinach, kohlrabi contain large quantities of nitrates, especially if they are preserved for more than two days, if they are thermally prepared or combined with proteins, resulting in nitrosamines that have carcinogenic potential.
A number of substances such as preservatives or those intended to give color, taste, flavor or a certain consistency can cause potentially mutagenic effects, which is why some of these have been removed from the market. For example, an increased content of saccharin determines bladder cancer in mice. There is no clear epidemiological evidence in humans concerning the involvement of saccharin in the etiology of cancers. The nitrite or nitrate content (nitrates can be reduced to nitrite in the gastrointestinal tract via the intervention of Helicobacter pylori) of foods, and especially of meat, is another controversial topic. The fact that nitrites combine with secondary amines to form nitrosamines in the gastrointestinal tract is an essential argument for diminishing the consumption of nitrite as food additives(3,4).
The factors in the diet can also play a protective role. Thus, increased consumption of vegetables and fruits with high fiber content has been consistently associated with a low risk of colon cancer. Such arguments are also available for stomach cancers and other epithelial cancers such as lung, pharynx, larynx, esophagus and breast cancers(3,4).
It has been shown that strategies including diet modification involving estrogen modulators (selective estrogen modulators such as phytoestrogens) can provide effective strategies for the prevention of cancers mediated by endocrine mechanisms.
Aflatoxin – a mycotoxin of Aspergillus flavus and A. parasiticus fungus, contaminating cereals (rice) stored under unsuitable conditions – has demonstrated a carcinogenic potential, particularly for aflatoxin B, in the induction of hepatocarcinoma(3).
The carcinogenic role of the hepatitis B and C viruses, as well as the presence of aflatoxin in food is correlated with the increased incidence of liver cancer in Asian and African rice-consuming countries (stored under humid conditions, rice is contaminated with the Aspergillus flavus fungus which secretes aflatoxin, a strong carcinogen involved in hepatocarcinoma etiopathogenesis)(3,4).
Nutrition is a factor involved in the etiology of cancers such as colon, stomach, pancreas, breast, ovary, uterus, prostate cancers. Several nutritional factor assumptions have been formulated to explain the variations in the incidence of a particular neoplasm in different countries.
Some substances (xenobiotics) from food have been associated with cancers, such as:
increased fat consumption (colon, prostate, endometrium and breast cancers);
polycyclic amines identified in well roasted meat have been involved in the development of gastric, colorectal, pancreatic and breast cancers;
high calorie diets (breast, endometrium, colon, prostate and gallbladder cancers);
animal proteins, particularly red meat (breast, endometrial and colon cancers);
alcohol, particularly in smokers (cancers of the oral cavity, pharynx, larynx, esophagus and liver);
salted diets with smoked foods (esophagus and stomach cancers);
nitrates and food additives (intestinal cancer)(4,5).
After reviewing all epidemiological studies in the last 30 years, The International Agency for Research on Cancer (IARC) concludes that obesity represents a causal link for various forms of cancer. It is believed that obesity causes death in one of seven men and in one in five women in the USA, while in the European Union it causes 4% of male cancers and 7% of cancers in women. The association between obesity and various cancers is complex(6).
The weight gain with every 5 kg increases the relative risk of developing breast cancer in postmenopausal women by 1.08. Increasing the Body Mass Index (BMI) by one unit increases the risk of breast cancer by 3%. In the USA, obesity contributes to the development of 20% of all postmenopausal breast cancers and to 50% of all postmenopausal breast cancer deaths(2,6).
Overweight is one of the most important risk factors for cancers such as colon, breast (after menopause), endometrium, esophagus (adenocarcinoma), pancreas, and kidney cancer; most likely, for gallbladder cancer also(2,6).
Typical cancers in relationship to obesity are:
a. Endometrial cancer – there is a strong correlation between obesity and uterine cancer. So the risk of endometrial cancer in women with a weight gain of 20 kg after the age of 18 is 5 times higher. Both obesity and weight gain are associated with an increased risk of endometrial cancer.
b. Colon cancer – the incidence of colon cancer increases in obese people.
c. Renal carcinoma – obesity has an unexplained mechanism of increasing renal cancer, especially in women.
d. Esophageal cancer of the adenocarcinoma type – obesity is considered to increase the risk of esophageal adenocarcinoma, with the increase in the prevalence of gastroesophageal reflux and the consecutive development of the Barett esophagus (metaplastic precursor lesion) of adenocarcinomas. Some studies have shown that obesity contributes to the increase of esophageal carcinoma independent of reflux disease.
e. Other cancers that associate a lower risk with obesity are: pancreatic cancer (it doubles the risk), hepatocellular carcinoma, cardial gastric cancer (due to gastroesophageal reflux with Barett metaplasia), ovarian and cervical cancer (limited data) and lymphomas; further studies are needed to fully define these relationships(4).
Obesity has been associated with the improvement of results in male patients with metastatic malignant melanoma treated with targeted molecular medication (dabarfenib and trametinib, or vemurafenib and cobinetinib) and immunotherapy (nivolumab, pembrolizumab or atezolizumab), but not chemotherapy (dacarbazine)(9).
The pathophysiological mechanisms by which obesity increases the risk of developing cancers are poorly understood.
There is evidence that associates the physical inactivity and obesity with an increased risk of developing colon cancer. Several studies suggest that the association between lifestyle factors and colon cancer is mediated by hyperinsulinemia and insulin resistance via the insulin-like growth factor (IGF)(6,7).
Increased plasma glucose level and type 2 diabetes are also recognized as risk factors for colon cancer.
Two main mechanisms are incriminated:
endocrine disturbances such as the installation of insulin resistance;
metabolic changes (metabolic X syndrome)(2,6).
Factors that influence cancer-obesity relationship
The risk of cancer attributed to excess body mass (Body Mass Index; kg/m2) in Europe is estimated at 3% for men and 9% for women. An increase in these cancers is estimated due to the dramatic increase in BMI in the population. Normal BMI values are considered between 18% and 25%(2,6,7).
Optimal physical activity is relevant in the primary and secondary prevention of colorectal and breast cancers. Independent of other factors, physical activity reduces the risk of colorectal cancers and protects against postmenopausal breast cancers and endometrial cancer. The mechanism is not elucidated, but it is believed that the weight loss affects sex hormones and specific endogenous growth factors. Moderate physical activity is recommended equivalent to a physical activity of at least 30 minutes per day, for obese people being recommended 60 minutes a day(7).
Since dietary factors have been estimated to be involved in about 40% of all cancers (according to World Health Organization), it has been suggested that certain dietetic strategies involving foods containing modulators of estrogen activity (e.g., phytoestrogens) may be an important method of preventing endocrine-mediated cancers(3,4).
Products of plant origin
Most foods with a protective role against cancers are of plant origin. The consumption of starch-free vegetables protects against upper gastrointestinal cancers – oral cavity, pharynx, larynx, esophagus (epidermoid carcinomas only) and gastric (adenocarcinoma), colorectal, pancreatic, breast and bladder cancers. Fruit consumption protects against oropharyngeal, oesophageal, colorectal and bronchopulmonary cancers. Garlic probably protects against colorectal cancers, and the consumption of tomatoes protects against prostate cancers (through the lycopene content). Vegetables and fruits are sources of fiber, vitamins and phytochemicals.
The protective effects of vegetables and fruit are also due to the content of dietary fibers, specific vitamins, and bioactive components such as carotene (red vegetables), folate (green vegetables), glucosinolates (brassica) and alkyl sulfates (garlic)(3,4).
The current recommendations state a consumption of 400-800 g/day of vegetables and the consumption of two fruits per day.
Some recommendations on vitamins:
Fruits with the highest levels of natural antioxidants are: strawberries, wild strawberries, raspberries, blackberries (“small and red fruits”).
Natural antioxidants are vitamins C, E and A, coenzyme Q, lycopene, melatonin, quercetin, selenium and zinc.
Vitamin C has a powerful antioxidant and anti-cancer effect, and is present in fruits like berries, rosehip, broccoli, red cabbage (because all vitamins are photosensitive, fruits must be stored in the dark).
Thiamine and vitamin C are sensitive to heat. Vitamin C protects vitamins A, E and B complex, and increases the absorption of iron and folic acid. A balanced consumption of fresh vegetables and vegetables cooked at low temperatures is preferable!
Vitamin A is found as ß-carotene in carrots, spinach, broccoli and green cabbage. Heavy smokers (with more than one pack of cigarettes per day) should not consume vitamin A supplements because this vitamin increases the risk of bronchopulmonary cancer.
Vitamin E is present in polyunsaturated fatty acids from eggs, meat, fish, but also in cereals, seeds, nuts, soybeans. Some studies suggest a protective effect against prostate cancer.
Lycopene is found in tomatoes when heated slowly over longer periods of time.
Selenium is an essential element found in organic and inorganic forms, in cereals, meat, fish or eggs; elevated levels of selenium correlate with low risk of prostate cancer and reduced incidence and mortality by cancer in general(3,4).
Vegetables such as endive, celery, lettuce, spinach and parsley have an increased content of nitrates when stored for more than two days, especially in winter: when these vegetables are heated and combined with proteins, nitrosamines result, which are potentially carcinogenic(9).
A diet rich in dietary fibers can lower the risk of breast, colon, rectum and pancreas cancers. For these reasons, a consumption of 600-800 g/day is recommended.
Starch-free vegetables have a low energy content, and a diet rich in these products protects against weight gain. Current recommendations are to consume at least 400 g/day of starch-free vegetables, fruits or unrefined seeds in five daily servings. It is recommended to limit the consumption of refined products with increased starch concentrations(8).
Patients with stage III operated colorectal cancers who regularly consume nuts or peanuts at least once a week demonstrate a 42% improvement in disease-free survival (DFS) and a 57% increase in overall survival(10).
Consumption of red meat
Consumption of red meat (beef, pork, lamb and horse), as well as processed meat products (red meat preserved in smoke, roasting, salting or adding preservatives – such as salami, ham, pemmican, bacon etc.) increases the risk of colorectal, breast, pancreatic, renal and prostate cancers. Red meat consumption more than once a week increases the risk of colorectal cancer by about 40%. For processed meat, the risk of colorectal cancer increases by about 20% for every 50 g/day(3,4).
One of the potential mechanisms involved in the risk of eating red meat (including fresh meat) could be the increased iron content of hemoglobin that could have an irritating effect on the colorectal mucosa and electrophilic aggression, which causes the initiation of carcinogenesis. Another mutagenic effect could be due to aggressive xenobiotic substances resulting from the thermal processing of foods (such as aromatic polycyclic hydrocarbons) with a definite role in carcinogenesis. Nitrates and nitrites added for food preservation can form carcinogens via the N-nitroso component. These components can form endogenously in the intestine by degradation of amino acid products (e.g., from meat) by reacting with nitrates or nitrites, a reaction that can be catalysed by the iron-containing heme from red meat. It is recommended to limit the consumption of red meat to 500 g/week (5 servings of meat/week) and avoiding the consumption of roasted meat(11,12).
Norat published a European study that included a population of 478,040 men and women followed-up between 1992 and 1998 (4.8 years), observing a strong correlation between the high consumption of red or thermally transformed meat (more than 160 g/day) versus lower consumption (less than 20 g/day) and the incidence of colorectal cancer, that is increased by 35% in those who consume higher amounts of red meat. On the contrary, comparing the increased consumption of fish meat (more than 80 g per day) versus lower consumption, he observed a 31% reduction in the risk of colorectal cancer(13).
Men consume more often and in larger quantities alcoholic beverages. Also, ethanol consumption is age-related: it is increased in adults and it is declining in elderly. The economically underprivileged social classes tend to consume cheap alcohol products. In Europe, the recommended limit for the consumption of ethanol is 20 g for men and 10 g for women (one drink = 10-13 g of ethanol)(4,11).
According to World Health Organization, alcohol consumption is among the top 10 risk factors, being in a causal relationship with cancers of the oral cavity, pharynx, larynx, esophagus and liver. Alcohol acts synergistically in combination with smoking in determining some of the aforementioned cancers. In case of liver cancers, there are strong arguments that it causes cirrhosis, which is a determining factor of hepatocarcinomas, due to the action of chronic lesions caused by alcohol abuse. The association between alcohol consumption and the increased risk of breast cancer is attributed to the association with estrogen action(2).
Major enzymes involved in ethanol metabolism are: alcohol dehydrogenase (ADH), which oxidizes ethanol to acetaldehyde, and ALDH (aldehyde-dehydrogenase), which metabolizes acetaldehyde to acetate. The homozygotes of the ALDH2 allele, whose product is inactive, are usually abstinent because the absence of the enzyme causes significant facial erythema, physical discomfort and severe toxic reactions. Heterozygotes have no severe side effects, but have an increased risk for alcohol-induced neoplasms(2).
Alcohol is a carcinogen substance because it is metabolized by the alcohol dehydrogenase enzyme to form acetaldehyde, which binds directly to DNA, forming mutant DNA adducts. Alcohol exerts its carcinogenic effects through tissue lesions (such as liver cirrhosis and chronic inflammatory status), or by facilitating assimilation of carcinogens into the exposed tissues (in oral cavity and esophageal cancers). Other possible mechanisms are: a) the content of N-nitrosamines in alcoholic beverages, b) the action of solvent that facilitates the absorption of carcinogens from cigarette smoke, and 3) the carcinogenic effect due to acetaldehyde, the major metabolite of ethanol. At a daily consumption of 50g of pure alcohol, there is a relative risk of 1.5 of breast cancer compared to non-consuming women. The same amount of ethanol increases the relative risk of colon and rectal cancer by 1.4. There seems to be no relationship with stomach, pancreas or lung cancers. About 3.6% of cancers worldwide, including 7-19% of oral cancers, are attributed to alcohol consumption(2).
Preservation, processing and the preparation of food
Some methods of preserving, processing and preparing food can increase the risk of cancer. Salt and the process of food preservation through salting are very likely to be one of the causes of gastric cancer. There is an increased salt consumption associated with preservatives used for meat and fish in some countries (e.g., smoke preservation). Current recommendations are to avoid foods preserved in salt and to provide less than 6 g of salt per day (2.4 g of sodium)(13).
Other food groups
Phosphoric calcium could reduce the risk of colon cancer by binding bile acids and free fatty acids, blocking their action on the intestinal epithelium.
Milk consumption could increase the risk of prostate cancer by increasing blood calcium levels and insulin-like growth factor-1 (IGF-1). Increased levels of calcium inhibit the formation of 1.25-dihydroxyvitamin D, that could stimulate prostate cell proliferation(14). A study showed that men consuming EPA, DPA and DHA, the three fatty acids from fish oil, have a 43% increase in the probability of developing prostate cancer.
Once again, it is demonstrated that excess nutritional supplements can be dangerous(15).
Omega-3, polyunsaturated fatty acids from fish oil, has a protective role against some cancers and a cardiovascular protective role. However, one study draws the attention to the fact that an increased consumption of omega-3 fatty acids may increase the risk of prostate cancers(15).
A recommendations guide on reducing the incidence of cancer via dietary measures is presented in Table 1.
Exposure to exogenous factors, including natural products or agents of industrial products present in water, soil and food, increases the risk of cancer, although the cancers caused by these agents are far less common compared to lifestyle-related factors, including the diet(16).
The link between cancer and diet is as complex as the neoplastic disease itself. Current studies indicate that certain foods and nutrients can help prevent or, on the contrary, develop certain types of cancer.
Although there are many factors that increase the risk of cancer, and which cannot be changed, such as genetics and the environment, there are others that can be controlled. In fact, current estimates suggest that less than 30% of a person’s cancer risk results from factors that cannot be controlled. For other risk factors we have the possibility to change them, including diet.
Conflict of interests: The author declares no conflict of interests