Obesity and its Relationship to Cancer: The consequences of carrying around that extra baggage
by Rachel Corbitt*
In the waiting room on the seventh floor of Emory University Hospital Midtown is a wide window overlooking the Atlanta skyline. The broad view isn’t the only noticeable feature of the waiting room. The seats of the chairs are also a bit wider than expected. This is the Emory Bariatric Center, where professionals help patients form individualized plans for losing weight.
The importance of achieving a healthy weight cannot be overstated considering that a bigger waistline means a bigger risk of cancer and other diseases 1. The center, however, receives very few patients sent from oncologists. “It’s a shame that we don’t get more,” says Medical Director of the Emory Bariatric Center, Dr. Arvinpal Singh. “It’s a critical issue and there’s a strong correlation between diet, obesity and various cancers, but I can’t say we’ve gotten a whole lot of referrals for that specific reason.”
Approximately 35% of men, 40.4% of women, and 17% of youth (ages 2-19) in the United States are obese, according to reports published in 2016 by the Journal of the American Medical Association 2, 3. Hospitals can’t even accommodate some of these patients. “Some of the scanners we have need to be bigger because a lot of our patients don’t fit through the CAT scans and the MRIs,” says Dr. Ira R. Horowitz, Chairman of the Department of Gynecology and Obstetrics at Emory University Hospital, “and they have to go elsewhere for an open MRIAlso: nuclear magnetic resonance imaging (NMR). Magnetic Resonance Imaging is a non-invasive imaging procedure that utilizes strong magnets and radio waves to visualize tissues. Subtle differences in the ways that the tissues and organs absorb and reflect the waves enable the detection of many different disorders., or to the zoo, or to the vet school.”
Patients who are unable to keep track of an expanding waistline have an increased likelihood of developing tumors. For those who already have cancer, obesity makes treatment more limited and problematic. The American Cancer Society estimates that a fifth of all cancer deaths are caused by excess weight 4.
“Some of the scanners we have need to be bigger because a lot of our patients don’t fit through the CAT scans and the MRIs, and they have to go elsewhere for an open MRI, or to the zoo, or to the vet school.”
Researchers report growing evidence that obesity alters the body in ways that can directly lead to cancer. Adipose, or fat tissue, produces molecules that are released to the rest of the body 5. Some of these molecules, including hormones like leptin, can trigger tumor growth 6. Fat tissue doesn’t just keep people warm and store energy says cancer researcher Dr. Latonia Taliaferro-Smith.
“What we’ve come to learn is that in addition to those roles, adipose and fat tissue actually secrete biologically active molecules,” explains Smith, a breast cancer specialist at Winship. “And these biologically active molecules, the majority of them are pro-tumorgenic. They promote cancer growth.”
Body weight impacts the production of these molecules and can affect whether or not someone develops cancer. In her studies, Smith found that two molecules secreted by fat tissue, adiponectin and leptin, work in opposite ways with respect to breast cancer 7.
Leptin, which is present at high levels in obese patients, can stimulate breast cancer cells to grow and invade other tissues 8. Adiponectin, however, serves a protective role against obesity-related diseases like cancer 9.
Adiponectin does a couple things to prevent high leptin levels from causing problems in the body. It stops the activation of two molecules (ERK and Akt) that are normally turned on by leptin and that would lead to cancer progression 7. Adiponectin also increases the activity of a tumor suppressorA gene that functions in the control of cell division. Tumor suppressors normally work to limit cell division and may be contrasted with oncogenes. geneA stretch of DNA that leads to the production of an RNA. The RNA is produced during the process of transcription. This RNA can be used to guide the formation of a protein via translation or can be used directly in the cell. called LKB1. The LKB1 proteinOne of the four basic types of biomolecule. Proteins are polymers made up of strings of amino acids. Proteins serve many functions in organisms including transport of molecules, structure, cell adhesion and as signaling molecules such as hormones. Many transcription factors, including p53 and Rb are proteins. prevents leptin signaling from occurring in the first place 7, 9.
Epidemiological studies have shown, however, that patients with a high body mass index (BMI) tend to have relatively low levels of adiponectin and high levels of leptin. In contrast, lean patients have higher levels of adiponectin and lower levels of leptin 6, 7. “It’s definitely in the best interest of anybody in general, but especially breast cancer patients to reduce their fat level, reduce their BMI, and ultimately reduce their chance of getting metastaticThe term for a cancer that has spread beyond its point of origin. Metastatic disease is responsible for the majority of cancer deaths. tumors,” says Smith.
Another fat-derived molecule that has been shown to promote the growth of cancer cells is the hormoneA chemical produced by cells that alters the activity of other cells. The chemicals may be lipids, such as testosterone and estrogen or proteins like insulin. Hormones may act at locations far from their site of origin. Estrogen, for example, is produced primarily by cells in the ovaries but acts on cells in the breast and elsewhere. estrogenA steroid sex hormone. Estrogen's structure is closely related to cholesterol. Produced by the ovaries, estrogen has effects on the reproductive, cardiovascular and skeletal systems. Estrogen is also a growth factor for some types of cells, including breast cells. Inhibitors of estrogen function such as tamoxifen and arimidex are used to block the growth effects of estrogen. See also, estrogen receptor.. In fact, the cancer drug tamoxifen is effective in breast cancer because it blocks estrogen receptors on breast cells. This action prevents these cells from being over-activated by estrogen 10.
Estrogen therapy has been used as a treatment for symptoms of menopause. During menopause, production of the hormones estrogen and progesterone by the ovaries is halted. The resulting lower estrogen levels cause the hot flashes, vaginal dryness, and increased osteoporosis risk associated with menopause 11.
In terms of endometrialRefers to the endometrium, the inner lining of the uterus. The endometrium is a common site of cancer. cancer, however, estrogen replacement alone turned out to be dangerous when not given in combination with progesterone 12. “If you just have unopposed estrogen, what you end up with is stimulation of the lining of the uterus, and then conversion to a cancer,” explains Horowitz. “We no longer give unopposed estrogen, meaning we give you estrogen and progesterone, which is going to mimic more of the physiology in your body.”
Obesity can lead to excessive estrogen levels because fat tissue produces a protein (aromatase) that converts precursor molecules into estrogen 13. “That just now results in estrogen that’s stimulating the breast, stimulating the uterus, increasing your risk of cancer,” says Horowitz.
InsulinA protein hormone secreted by the pancreas. Insulin controls glucose levels in the body by increasing uptake of glucose into cells of the body. Insulin also stimulates the formation of glycogen and alters fat and protein metabolism.-like growth factorA substance that stimulates cell division. Growth factors are usually small proteins or steroid hormones. They may be secreted by the same cells on which they act or by cells that reside in a different part of the body than the target cells. Some examples of growth factors include estrogen, a growth factor for breast cells, and VEGF, a growth factor that causes the development of blood vessels. Several different anti-cancer treatments are designed to inhibit the activity of growth factors.-1 (IGF-1Insulin like growth factor type 1. A potent growth factor. Elevated levels of IGF-1 have been found in the blood of patients with certain types of cancer, including breast cancer.) is an additional bioactive compound secreted by adipose tissue. When this compound binds to a tumor cell, it triggers a signaling pathway that leads to cell division 6. “When you are an adult, your cells aren’t really supposed to be growing and growing and growing because you’ve reached your adult size,” says Singh. “Anything that’s stimulating uncontrolled growth of cells can lead to cancer.”
Too much of this growth factor is especially bad when the patient also has insulin resistance, which is often the case for obese people 8. The cells in a patient with insulin resistance don’t respond to insulin to the extent that they should. To compensate, the pancreas churns out even more insulin. Insulin then goes and prevents other proteins from binding to and blocking the growth factor IGF-1 14, 13.
In other words, the extra insulin molecules in obese patients make the growth factor better at finding and triggering cancer cells.
Between producing many biologically active molecules, including carcinogenic levels of leptin, estrogen, and insulin-like growth factor-1, fat cells stay busy. They certainly aren’t sitting silently on the waistline of America.
“Adipose and fat tissue actually secrete biologically active molecules, and these biologically active molecules, the majority of them are pro-tumorgenic—they promote cancer growth.”
After a patient’s cancer diagnosis, obesity complicates the work of the surgeon 15. “I might want to give them radiationIn cancer biology: A cancer treatment in which high energy beams are used to kill cancer cells. Radiation can also cause genetic damage that can lead to cancer. As an example, skin cancer is believed to be greatly increased by exposure to ultraviolet (UV) radiation from the sun. or hormones before I operate on a 500-pound patient,” says Horowitz. “It’s hard. You can’t see, they bleed more, and you can cut other organs.”
Putting these patients under anesthesia is especially tricky. “We’re learning more and more now when we’re looking at those patients who are high risk to have problems with anesthesia, [it’s] because they’re obese patients,” says Horowitz.
Many patients with obesity suffer from obstructive sleep apnea, which means their airways are obstructed by excess fat tissue 16. Intubation with a respiratory tube on these patients is more difficult for the anesthesiologist 17. The extra tissue also blocks airflow and limits the amount of oxygen the patients can receive during and after sedation 15.
Anesthesiologists have to be especially cautious when administering sedatives to obese patients. These patients show less predictable responses to medications. Plus, the anesthetic drugs require more time to disappear because the drugs linger in the fatty tissue 18.
The large body mass of obese cancer patients also poses a difficulty when prescribing chemotherapyTreatment of cancer patients with anticancer drugs. Commonly called 'chemo'. These drugs work by attacking cell growth or division. Often these agents are used in combination to take advantage of their different modes of attack on cell division. dosages. The clinical trials needed to determine standards haven’t been performed. “Do we know what the bioavailability of that drug is going to be with someone who weighs 500, 700 pounds? No,” says Horowitz. “We don’t have the thousand people who weigh 600 pounds.”
That isn’t to say those thousands of people don’t exist. Over a third of Americans are overweight or obese 2. Singh emphasizes that this isn’t simply a personal problem for Americans. “I think that’s a gross oversimplification. We live in what a lot of people call an obesogenic environment or an obesogenic society,” comments Singh. “Everything in our society is geared towards promoting weight gain.”
Specifically, Singh refers to the high density of fast foods in lower socioeconomic areas, unhealthy foods being cheaper or more affordable than healthier foods, subsidies to processed products versus a lack of subsidies to organic and fresh whole foods, junk food advertisements on billboards, faulty food guidelines, the involvement of the meat and dairy industry with the government, and technology reducing physical activity. “I mean, so many factors. I could go on and on,” Singh says.
As for the genetic components of obesity and cancer, Singh cautions that it shouldn’t be blown out of proportion. “Genes aren’t what cause people to be obese. Genes just kind of load the gun for you, so to say.” Horowitz echoes this sentiment. “I think a lot of cancers we have some control over. It’s environment, it’s lifestyle, so that includes exercise, spiritual health, diet.”
Dr. Singh says patients can control their chances of getting cancer by forming responsible eating habits. “Hopefully they’re eating better, they’re eating higher-nutrient foods, and there are of course links to food and diet and cancer,” he says. “There is no medication or no pill patients can ever take that’s more potent that what food they put in their bodies.”
With special thanks to interview sources:
Dr. Arvinpal Singh, M.D.
Medical Director of the Emory Bariatric Center
Dr. Ira R. Horowitz, M.D.
Chief Medical Officer of Emory University Hospital
Chairman of the Department of Gynecology and Obstetrics
Member of Winship Cancer Institute and the Division of Gynecologic Oncology
Dr. LaTonia D. Taliaferro-Smith, PhD
Breast Cancer Researcher, Winship Cancer Institute
*The above feature story was contributed by former undergraduate of Emory University, Rachel Corbitt, for her "Health and Science Writing" class. Rachel majored in Biology and Chemistry and is currently attending the Medical College of Georgia at Augusta University.
Learn more about the role of obesity in cancer.
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