Harvard Reports on Cancer Prevention
Volume I: Human Causes of Cancer
Cancer Causes & Control:
An International Journal of Studies of Cancer in Human Populations
Official Journal of the International Association of Cancer Registries
Volume 7 Supplement November 1996 ISSN 0957-5243

Obesity

Introduction
In scientific literature, the term obesity is defined as the excess storage of energy in the body in the form of fat.¹ It is a term that often is used interchangeably with the word overweight, which implies weighing more than a standard level for a given height and gender. Accumulation of body fat is the way in which most Americans become overweight.

Body weight and fat content of human beings result from multiple interrelated factors, including health status, basal metabolism, diet, physical exercise, hormonal factors, race, and heredity.² Further, body weight and fat composition can change over time due to these same factors. Because of this, the timing (for instance, child hood, adolescence, or adulthood) or duration of obesity (recent compared with long-term) may be important to health risk. Some key questions that must be considered when studying the health risk of obesity are: How much extra weight or body fat is too much? Is the location of extra fat (for instance, on the abdomen or on the hips and thighs) important? Does height, which is correlated with weight, play a role? Is being overweight an indication of eating too much of certain types of foods?

The rise in the proportion of the adult American population that is overweight has given additional impetus to studying the health risks associated of being overweight. In studies over the period from 1971 to 1980, the overall prevalence was slightly over 25 percent, but by the late 1980s, the prevalence had increased substantially. Based on data collected by the United States National Center for Health Statistics from 1988 to 1990, Kuczmarski and colleagues³ found that about 31 percent of men and 35 percent of women in the US were overweight. Overweight has been defined as weighing more than 20 percent above the gender-specific 'ideal' weight as determined by the Metropolitan Life Insurance Company's 1983 height and weight tables. These types of increases are occurring in developed countries all over the world, including Great Britain, Canada, and Japan.^1,4 Improvements in the socioeconomic status of populations result in increased body size, both in height and weight.^4,5 (It is important to note that improvements in the standard of living over the last century have contributed greatly to increased life span by reducing infant and maternal mortality and mor tality from infectious disease. However, these improvements may contribute to chronic disease later in life.⁴) Although not all obese people develop chronic illness, as the number of obese people increases, the number who become afflicted with obesity-induced illness will also rise.

A landmark study on the relationship between cancer and obesity was conducted by the American Cancer Society.⁶ Over a 13-year period from 1959 to 1972, body weight, smoking, and cancer mortality information was collected for 750,000 Americans living in 26 states. After accounting for the effects of age and cigarette smoking, people whose body weight was 40 percent higher than average had an overall increased risk of cancer death—a 33 percent increase in men and a 55 percent increase in women. Overweight males experienced significantly higher rates of colorectal and prostate cancer; whereas, overweight women experienced higher rates of gallbladder, breast, cervix, endometrium, uterus, and ovarian cancers. Hundreds of other studies have been performed since then,^{2, 7-12} and many have had the same general result, linking obesity—at least mildly—to cancer, particularly these specific types. Not all studies have found such a link, however.

Around the world, colon cancer rates vary 20-fold,¹² and breast cancer rates vary fivefold (8). The highest rates are in the developed world - North America, Western Europe, and Australia. Age-adjusted colon cancer incidence rates in developed countries range from 25 to 35 per 100,000 people.¹² Breast cancer rates range from 50 to 80 cases per 100,000 in the same geographic areas.⁹ Historically, Mexico and Japan have had relatively lower rates of breast and colon cancer. However, among Mexican and Japanese immigrants to the US, cancer rates reach those of the US within one or two generations.^4,9,10 This implies that there may be something about the American or so-called Western lifestyle—such as becoming obese—that affects risk. On the other hand, colon cancer as well as breast cancer have long been known to occur more frequently in some families, and there are several rare genetic syndromes that carry an excess risk of colon cancer.^13,14 Thus, breast and colon cancer are complex diseases that may be the consequence of a combination of genetic predisposition, lifestyle characteristics, and even environmental exposures.

Obesity increases risk of breast cancer only among postmenopausal women.^7,8,15 For example, in a 1980 study of over 5,000 women in the San Francisco Bay area (California), those in the heaviest weight class had nearly a 40 percent increased risk of breast cancer compared with women in the lowest weight group.⁷ Most cases of endometrial cancer are also diagnosed in older women,⁷ but some studies report that obese younger women are more likely to develop endometrial cancer than leaner women.¹⁵

Estrogen has been shown to be an important growth factor for cells of the breast and ovary and has been implicated in cancer of reproductive tissues.¹⁵ Adipose tissue is capable of converting androstenedione (a major hormone secreted by the adrenal gland) to estrone, which is a form of estrogen.⁷ In fact, for postmenopausal women, this is the primary source of estrogen. Further, obese women tend to produce less sex-hormone-binding-globulin (SHBG), and postmenopausal women also produce less progesterone. These two hormones regulate estrogen's activity in the body.¹⁵ Thus, overweight, postmenopausal women may be exposed to relatively more estrogen, which could increase breast cancer risk.

Colon cancer has been associated consistently with increased consumption of red meat and some types of fats, decreased consumption of vegetables, and physical inactivity.^12,13 Most studies have shown that obese men are at higher risk of colon cancer but that obese women are not.^6,10,11 The reason for this gender difference is not known. One hypothesis is that men are more likely to accumulate fat tissue in the abdomen, while women are more likely to accumulate fat tissue around the hips and thighs.¹³ Abdominal fat is more biologically active (for instance, by affecting insulin levels). The risks associated with obesity may overlap somewhat with the risks of physical inactivity and nutrient intake.¹³ For example, some people gain weight when they eat more calories than they expend, in part because they are not physically active. Also, overweight people tend to consume more meat and fat than leaner persons.¹⁶

Insulin
Over the last several years, new research has begun to identify a potential common pathway by which adult obesity plays a role in causing both colon and breast cancer. The pancreas secretes insulin in order to help metabolize glucose and carbohydrates.^13,17 When a non-diabetic person consumes excessive calories and gains weight, tissues become insensitive to insulin, and the body becomes less able to convert glucose into energy and other metabolites. One study has shown a decline in insulin sensitivity (or effectiveness) of 30 to 40 percent when a person exceeds 35 to 40 percent above their ideal weight.¹⁷ The body compensates by producing more insulin, a condition called hyperinsulinemia. Many studies have shown that obese adults have much higher insulin levels in their blood than leaner people.

Insulin and insulin-like growth factors (IGFs) also have been linked to cell development and proliferation. IGFs have been identified as growth factors for colonic mucosal cells. They also play a role in the development of colonic carcinoma cells¹³ and mammary tissue development. Studies have shown that estradiol (a type of estrogen) and IGF work together in the development of certain types of breast cancer. Thus, chronic excessive exposure to insulin, brought about by obesity, may play a role in carcinogenesis.

Body frame size
Recent studies have also shown a link between adult height or body frame size and breast and colon cancer risk. Taller, larger framed people appear to have a some what greater propensity for disease.^4,5,8,13 Adult stature is a direct consequence of growth and maturation during childhood and adolescence. Height is determined genetically but also is influenced by nutrition and physical activity; therefore, weight and height trajectories during childhood and adolescence may influence adult cancer risk.

There are several ways growth and maturation could affect adult cancer risk. First, children who are obese are at a greater risk of becoming obese adults.⁴ Second, taller persons have been exposed to more growth factors.⁵ Third, people genetically inclined to insulin resistance and/or insulin hypersensitivity may be more likely to develop these syndromes during the normal gain in weight and height associated with puberty.⁵

Conclusion
The relationship between obesity and cancer is complex and not completely understood. It is likely that obesity in conjunction with other risk factors (such as menopausal status, low activity level, and predisposition to insulin resistance) places men and women at higher risk of disease. Many obese people will never develop cancer, and some lean people will be diagnosed with the disease. However, many studies indicate that the likelihood is greater among those who weigh more than 35 percent above their ideal body weight. For a woman whose recommended weight is 120 pounds, weighing 35 percent over the ideal would amount to about 40 additional pounds. Similarly for a man whose ideal weight is 180 pounds, 35 percent excess body weight would be about 60 additional pounds. It is possible that future studies will show that even smaller amounts of excess weight confer some risk of cancer.

Obesity is a well-established risk factor for many other diseases, such as stroke, cardiovascular disease, and diabetes.^2,17,18 Maintaining a healthy adult weight by eating well and exercising regularly will reduce the risk of these diseases and simultaneously may reduce cancer risk. Further, maintaining proper diet and weight gain during childhood and adolescence may reduce risk of cancer during adulthood.

Summary Points

Suggestions

Suggested Further Reading

References