|Julia Draznin Maltzman, MD|
|Abramson Cancer Center of the University of Pennsylvania|
At the start of a new year, many people resolve to loose those extra pounds gained during the past twelve months. In addition to the aesthetics of a lean body, and prevention of the diseases known to be associated with obesity such as diabetes, heart disease and stroke, there is a new and growing body of literature implicating cancer as another consequence of obesity. Cancers of the breast, colon, kidney, endometrium and prostate have well known associations with obesity. Recently, evidence has been growing implicating gall bladder cancer and certain types of esophageal cancer with obesity. Some associations are tenuous at best. For example, esophageal cancer is thought to be caused by chronic acid reflux, which occurs often in the obese patient. Reflux is certainly exacerbated by excess weight. However tenuous some associations maybe, research in animal models of cancer development, has undisputedly shown, that maintaining a lean body mass can and does delay the onset of cancer.
The most extensive data on the association of obesity with cancer has been published in the field of breast cancer. A nurses health study in Boston found that post menopausal women just 44 pounds overweight double their risk of breast cancer. Before menopause, the ovaries produce estrogen, a hormone that regulates the menstrual cycle and other sexual functions. After menopause, when the ovaries are no longer functioning, fat becomes the primary source of estrogen in the body. Exposure to estrogen has been proven to stimulate cells to divide and grow rapidly which can be associated with increased risk of breast cancer. Obesity is also considered a risk factor for pre-menopausal breast cancer. One thought is that hormones such as insulin and insulin-like growth factor 1 (IGF-1), that are present in excess amounts in the obese individual, promote rapid growth of certain breast cancers. Moreover, insulin and IGF-1 can lead to an earlier age at puberty and menarche (onset of menstruation). A younger age of menarche is a well-accepted risk factor for breast cancer. Some suggest that obese, post-menopausal, women, have excess estrogen and insulin, may more than double their risk of breast cancer.
Unfortunately, obese women are less likely to have their breast cancer tumors detected at an early stage. Delay in diagnosis can result in a less treatable stage of disease and therefore a worse outcome. Obese patients are also more likely to endure more complications with some common medical treatments such as surgery. Wound healing is impaired and overall survival is decreased in obese patients when compared with normal weight individuals.
Colorectal cancer is the third most common cancer in the US. In multiple studies, consumption of excess calories has been associated with increased risk for colon cancer. Unused caloric energy is stored by the body as fat. Excess fat eventually results in a condition known as insulin resistance. In normal, physiologic circumstances, the pancreas produces insulin to help muscle, liver, and brain cells metabolize glucose or carbohydrates. Muscle, liver, and brain cells of obese individuals are less sensitive to insulin. As a result, these people cannot convert the carbohydrates they eat into usable body energy for these cell types. The body tries to compensate for this by signaling the pancreas to make and secrete even more insulin. Insulin and its cousin, IGF-1 when present in such great amounts, act as growth factors and stimulate cells to grow and divide in much the same was as estrogen does. Some studies have shown that excess insulin stimulates colon epithelium cells to grow and divide rapidly and therefore increase the risk of colon cancer. The colon cancer risk that is associated with excess insulin seems to be more pronounced in men. Men tend to have most of their excess fat stored around the abdomen, as opposed to women who harbor most of their fat on their hips and bust. Abdominal fat, it seems, is associated with particularly high levels of insulin and IGF-1.
Endometrial cancer is generally seen in postmenopausal women and the fourth most common cancer in American females. Weight gain during adulthood seems to be associated most often with this type of malignancy. Prostate cancer, the most common cancer among men, is also associated with similar hormonal conditions. Centrally located fat inciting the production and secretion of insulin, IGF-1, testosterone, and other growth factors, may act to stimulate prostate cells to grow quickly and therefore increase the risk of cancer. Although rare, kidney cancer has a two-fold increase in relative risk in the obese population.
Multiple animal studies demonstrated that restricted caloric diets increase longevity and can prevent cancer. Some argue that this effect is due to a decrease in IGF-1 levels. IGF-1, a hormone, has many tasks, including formation of long bones during puberty and acting as a growth factor to many different cell types. This hormone has been associated with the development of colon, breast, prostate, lung, and ovarian cancers. Animal studies show that high levels of IGF-1 offer an advantage to tumor growth. Calorie restricted diets as well as exercise can reduce levels of IGF-1.
There is a protein called IGF-1 binding protein 3 (IGFBP 3) that binds IGF-1 thus preventing it from interacting with its complementary receptor. Some researchers suggested that high levels of this binding protein, therefore, might be protective in some IGF-1 driven cancers.
Researchers are looking at putative human obesity genes for insight as to how these may contribute to cancer. This task is made difficult by the fact that there are no obvious single mutation genetic aberrations responsible for obesity. Rather, obesity seems to be the result of the interaction of several genes as well as influences of life style and diet.
Risk of Death
The American Cancer Society (ACS) has recently released the largest study to date evaluating the relationship between cancer and obesity. This was a sixteen-year follow up of nearly a million men and women examining the link between baseline body mass and cancer. In this time period, 57,145 cancer deaths were identified among 900,000 participants. None of the people participating in this study had cancer at the time of enrollment. The study remarked that 14% of all cancer deaths among men and 20% of all cancer deaths among women were somehow associated with being obese or overweight. Obese men and women alike, demonstrated significantly more deaths due to cancer of the esophagus, colon, breast, rectum, liver, gallbladder, pancreas, kidney, endometreum, and non-Hodgkin?s lymphoma and multiple myeloma, than normal weight controls. The heaviest men were 52% more likely to die of cancer than their normal weight counterparts; and the most obese women were 62% more likely to die than thin/normal weight women. The implications of this study to the general public are enormous. This means, that in this country alone, 90,000 cancer deaths per year could be avoided by maintaining a normal body weight. The body mass index (BMI) is a measure of fat and is the weight in kilograms divided by the square of the height in meters. This is what physicians use to define obesity. A BMI of 18.5-14.9 is considered to be normal. Overweight and obesity are defined by BMIs of 25.0-29.9 and >30.0 respectively.
A more recent study out of Johns Hopkins showed that people with impaired glucose tolerance, as in obesity, have an increased adjusted relative risk of cancer mortality. The authors concluded that in the U.S., impaired glucose tolerance is an independent predictor for cancer mortality.
Exercise has been shown to reduce the risk of multiple cancers in various studies. A more recent study conducted by a researcher at the Fred Hutchinson Cancer Research Center in Seattle looked at physical activity in approximately 75,000 women around the US and compared it to the incidence of breast cancer. Women who participated in regular physical activity at the age of 35, had a 14% decreased risk of breast cancer. Similar studies for other malignancies have consistently shown physical activity to be protective against cancer.
Our wishes to you
We, at OncoLink, wish you all much luck and success with all of your New Year resolutions.