Researchers discussed an update on the latest evidence regarding the cancer-lifestyle link as part of the Precision Health session: Oncology, held during the 7th International Congress of the Spanish Society of Precision Health (SESAP). The role that certain nutrients can have on tumor development was analyzed, along with the most recent data justifying the idea that the prescription of physical exercise should not be optional, but rather integrated into oncological treatment.
“Diet and lifestyle can have an influence on each of the successive stages that occur in the carcinogenesis process: initiation, promotion, and progression. Although nutritional factors and factors related to daily habits are more or less the same, the impact of these at each phase is different,” explained the dietician-nutritionist Pedro Carrera Bastos, a doctoral candidate and researcher in nutrition, metabolism, and inflammation at Lund University, Sweden. Carrera analyzed this question in his presentation “Diet and Habits in the Prevention of Carcinogenesis.”
“A deficit of certain nutrients is one of the nutritional factors that are involved in the initiation phase, including folate and B group vitamins (B12, B6, B3), which leads to chromosomal ruptures, DNA hypomethylation, and increased sensitivity to mutagens,” said Carrera. “As for vitamin C and selenium deficiency, this increases oxidative DNA damage, an effect that is also associated with inadequate levels of zinc and magnesium and vitamin D deficiency.
“We have also seen that aflatoxin has a negative impact in the initiation phase. It is present in foods of vegetable origin, such as cassava, pepper, corn, millet, rice, sorghum, wheat, sunflower seeds, or peanuts, although its effect largely depends on the way in which these foods are stored,” added Carrera.
Yet among all these agents, those most involved in this carcinogenesis phase are undoubtedly nitrous compounds, nitrites and nitrates in particular, he explained. “Those present naturally in food do not cause cancer, because biochemically they do not produce nitrosamines. We have a problem with nitrites that are added, for example, to processed meats or to sausages; these do produce nitrosamines.”
Polycyclic Aromatic Hydrocarbons
Contextualizing the link between nitrosamines and carcinogenesis, Carrera noted that these substances are also present in tobacco, although with clear differences regarding their knock-on effect. “In fact, when the effects of tobacco are compared with the effects of consuming processed meat, we see that 72% of lung cancer cases and 15% of all cancers are due to the habit of smoking, while consuming processed meat is associated with 13% of intestinal cancer cases and 1.5% of all cancers.”
The specialist stated that there are two particularly harmful types of processed foods: cured meat (which has N-nitroso compounds) and smoked meat and fish, which contain polycyclic aromatic hydrocarbons, chemical substances directly related with certain cooking methods. “We know that polycyclic aromatic hydrocarbons are formed when cooking foods of animal and also vegetable origin, since it is pyrolysis, both of organic material as well as of lipids and proteins, that generates these substances.”
To illustrate the role that the various cooking methods play, Carrera analyzed the results of one study carried out in China in which polycyclic aromatic hydrocarbons of animal and vegetable origin were compared when raw and after being grilled. “The authors observed that the increase of polycyclic aromatic hydrocarbons was much more significant in foods of animal origin. Likewise, they found that among the meats, chicken is the most prone to the formation of polycyclic aromatic hydrocarbons.”
The study also highlighted that it is possible to reduce the formation of these substances using various strategies. One strategy is “marinating the food in an acid solution for more than one hour, since through this, the formation of these hydrocarbons is reduced, as are the final products of advanced glycation, which are prooxidants and proinflammatory,” said Carrera. “Another option is to season the meat and fish before grilling them (with pepper, paprika, garlic, onion, ginger, turmeric, cumin, cinnamon, clove, fennel, star anise), cooking at a low temperature (boiling is one of the most beneficial techniques) and above all, eating the meat or fish together with a large amount of vegetables, especially from the brassica family (broccoli, cabbage, kale, turnip, brussels sprouts, mustard).”
Objective: Stop Inflammation
Carrera explained the reasoning behind this recommendation. “Meat cooked on the grill may contain benzopyrene, a hydrocarbon that can cause a mutation in DNA, being an indicator of carcinogenesis. Meanwhile, brassicas are rich in sulforaphane, involved in an increased expression of certain genes, among them the one that codes for the expression of glutathione s-transferase, thus favoring the elimination of benzopyrene.”
The factors that can act as promoters and progressors of carcinogenesis are many and diverse. Among them are psychological stress and circadian disruption (as several studies have demonstrated regarding the effects of shift work), physical inactivity, obesity, hyperglycemia, hyperinsulinemia and increase in concentrations of insulin-like growth factor 1 (IGF-1)/insulin-like growth factor-binding protein 3 (IGFBP-3), dysbiosis, and vitamin D deficiency.
The common element or “guiding thread” of all these factors is inflammation, since we know about active inflammatory response by various mechanisms, gene expression involved in apoptosis, increased angiogenesis, cellular proliferation, etc. “As we were able to verify in a study conducted on this topic, among the main causes of chronic systemic inflammation, we find obesity, physical inactivity, circadian disruption, chronic psychological stress, exposure to various xenobiotics or an inadequate diet,” said Carrera. “All of this can activate various proinflammatory routes, contributing to carcinogenesis.”
In parallel to the evidence on the role of inflammation on the phases of tumor promotion and progression, there is also more and more data on nutritional or lifestyle elements that can prevent or stop this effect. “One of said elements refers to fatty acids from the omega-3 family (EPA, DHA), that can bind to a transmembrane receptor, inhibiting activation of kinase proteins,” said Carrera. “These acids are a solution, especially in patients with chronic systemic low-level inflammation. There are also various phytochemicals present in foods such as ginger, green tea, turmeric, and broccoli and other brassicas that can inhibit phosphorylation of kinase proteins. But what is really important is identifying the causes of low-level chronic inflammation in each one of the patients and acting in accordance with these. This is the key objective. Likewise, lifestyle changes are much more relevant than thinking about concrete nutrients or substances, since daily rituals determine our health,” he concluded.
Exercise as Oncological Therapy
In the same session, Adrián Castillo García, graduate in physical activity and sports sciences and a researcher at the Barcelona Biomedical Research Institute (IIBB) of the Spanish National Research Council (CSIC), reviewed the latest studies that showed evidence of the importance of physical exercise during cancer treatment and its potential role in modulating the tumor microenvironment and immune function.
In his presentation “Cancer and Physical Exercise: A Battle Between High Performance Cells,” the specialist commented on the connecting points between the physiology of exercise and the physiopathology of cancer. He believes that this is an emerging field, starting more than 10 years ago and in which there are still many things to discover. “We should widen this field of study to provide clinical reasons why physical exercise would have to be an essential treatment in oncological patients,” Castillo stated.
“Cancer is a disease with a clear metabolic component, and the tumor microenvironment determines in part the development and malignancy of the disease,” he continued. “In this framework, we know that hypoxia is one of the main triggers of tumor aggression, leading to a vicious cycle that encourages protumor mutations. Therefore, it is essential to reduce levels of hypoxia in the fight against the disease. The goal of any therapy is to modulate the tumor microenvironment and metabolically combat the tumor with the aim that the treatments be much more effective.
Castillo highlighted the results of one of the more recent studies on this topic, which demonstrated that physical exercise, in combination with chemotherapy, reduces progression and tumor volume. The results position exercise as an important optimizing element of the main treatments that are applied to these patients. “Additionally, the only studies conducted on humans (concretely, in the case of pancreatic cancer) demonstrate that exercise remodels the vascular structure, even when it is recommended (in small doses) to be conducted at the home of the patient.”
Regarding the most adequate type of exercise to achieve this effect, in the opinion of Castillo, the best mitochondria that are “washers” of lactate are those associated with resistance exercise, such as cycling.
“Therefore, prescribing doses of physical activity at an established intensity and volume can be very decisive in combating the tumor microenvironment, but this preliminary evidence must be confirmed in trials on humans to ratify the role of exercise as a treatment capable of improving the efficacy of the main therapies,” concluded Castillo.