The obvious but still unanswered link between obesity and cancer
The second leading cause of death in the United States is cancer.1 Many studies are performed or in progress to prevent cancer, improve treatment and/or prolong life expectancy for people diagnosed with cancer. It has been shown that several diet patterns and components, particularly those of which are considered to promote obesity, are related with increased cancer risk. More than 30% of the cancers could be prevented with exclusion of these diet patterns and habits.2 The American Institute of Cancer Research even listed seven obesity-related cancers, including breast cancer, colorectal cancer, endometrial cancer, renal cancer, gallbladder cancer, esophageal cancer and pancreatic cancer.2 This correlation seems obvious since obesity causes an increased risk of multiple chronic diseases, including type 2 diabetes, chronic inflammation and various types of cancer. Furthermore, obesity patients possibly have a lower response rate to anti-cancer therapies.3 The connection between nutrition science and scientific cancer prevention research has been found in multiple literature studies but the scientific results regarding the mechanisms are not well described. This review highlights the different kinds of studies done regarding the obesity-cancer link.
Multiple nutrition studies examine the obesity-cancer link with the aid of the body mass index (BMI). Hakimi et al. investigated the relationship between BMI and cancer-specific mortality looking at molecular tumor features and nutrition status. Their statistical results suggested that tumors which were developed in obesity patients may be more indolent.4 However, scientific researchers contradict this method. Hopkins et al. claimed that BMI refers to the amount of adiposity but ignores the unit of weight composition, which differs in cancer patients. Furthermore, the BMI value of smokers is usually lower than the value of non-smokers. This is contradictory, since it is generally known that smoking also induces oncogenetic processes that could cause cancer development. 5 This leads to unreliable results.
Recent technologies were developed for advanced monitoring of tumor progression in patients and accurate measurements for adiposity, bones and muscle mass and led to new insights concerning the obesity and cancer link.5 Hopkins et al. found that the signaling network, which maintains energy balance, is dependent from the adipose tissue and communicates via the hormonal endocrine system. The hormone insulin is responsible for multiple processes, for example, the glucose metabolism and influence the glucose uptake, activation of protein synthesis and growth factor signaling. The growth factor signaling functions via the insulin-like-growth factor (IGF) which regulates growth and development processes by promoting growth and/or survival of cells. Because of the excessive adiposity, the functions of the IGF could impact many cancer cells developing processes including continued proliferative signaling and inhibition of anti-growth signals.5
Smith et al. suggested two other mechanisms concerning
the obesity-cancer link. Cancer cells need more glucose for adenosine triphosphate (ATP) production explained in the "Warburg effect". Energy, in the form of glucose, is stored as lipid in adiposity tissue, so more glucose is available for ATP production in obesity patients. From this, it can be concluded that cancer cell growth is fueled by obesity.6 Hopkins et al. confirmed these results and added that the growth of cancer cells is also fueled because of the availability of surplus amount of substrates for lipid membrane generation and ATP production.5 Another cancer stimulating process induced by obesity is autophagy. Autophagy is a process which provides the cancer cells to proliferate during low nutrient circumstances through the digestion and recycling of the cellular substances. A combination of calorie restriction and autophagy inhibition resulted in reduced tumor growth.6 These results are promising for an extensive research concerning dietary ways to prevent obesity-cancer development.
The extensive research was done by the nutrition sciences which investigated the influence of ketogenic diets to cancer prevention and treatment. Branco et al. showed that ketogenic diets can reduce the side effects of the chemotherapy. Furthermore, it resulted to an improved response rate to the chemotherapy. Patients will therefore require a lower dose of radiation therapy, which is less harmful to the rest of the body. However, they also stress the risks of the utilization of a ketogenic diet as potential for improved cancer therapy response rate.7 Hopkins et al. acknowledged the use of an ketogenic diet for improved cancer therapy but contradicts this study by claiming that ketogenic diets reduces body weight which increases toxicity to chemotherapy leading to reduced response to chemotherapy.5
In conclusion, different studies are performed to determine the link between obesity and cancer. It is stating the obvious to say that an unhealthy lifestyle, leading to obesity, stimulates obesity-associated cancer development. However, the intersection between nutrition sciences and cancer prevention research sciences regarding the obesity-cancer link, is not that obvious. A lot of nutrition sciences has been published regarding the obesity-cancer link, but research scientist claimed that these publications were not reliable because of their lack of large trials, big influence of small studies and inconsistencies.8 The inconsistencies were, for example, various exposure levels and durations, different eating patterns and small cohorts leading to unreliable statistical results. The literature regarding research findings in nutrition sciences should be ordered hierarchically by the number and quality of evidence.
Cancer prevention research scientists showed that obesity induces various signaling pathways involving oncogenic processes. Several dieting methods for reduced body weight are described by nutrition sciences for induced response rate to cancer treatments. However, research scientists rejected these methods because these results were from poorly designed trials or resulted in an increased sensitivity to chemotherapeutic toxicity. Moreover, obesity is often not the only cause of cancer, other factors, for example, smoking, alcohol consumption and family history, could also induce the mechanisms described by the scientific researchers. The correlation and mechanism between obesity, without the influence of the other risk-factors, and cancer is therefore difficult to determine. This gap in the literature should be further explored. More research is required to track down this mechanism and discover new therapies to prevent cancer development and/or improve the quality of life of cancer patients. A suggestion would be to assemble a multidisciplinary team consisting of, for example, oncologists, nutritionists and cancer biologists, for the design and procedure of clinical trials.