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Leslie Bernstein, PhD
Professor, Preventive Medicine
AFLAC, Inc. Chair in Cancer Research
University of Southern California/Norris Comprehensive Cancer Center and Keck School of Medicine
Los Angeles, California

The US and other developed countries are experiencing two parallel and interrelated epidemics, one of obesity and one of physical inactivity. Obesity is associated with a number of chronic diseases including cancer, but regular physical activity helps avoid weight gain and by itself may reduce risk of these diseases.


The Problem Starts Early

During the past two decades, the percentage of overweight adolescents in the US increased more than 3-fold, from roughly 4% to just over 15%; the same dramatic increase occurred in children between age 6 and 11 years-from 5% to over 15%. Part of the problem is physical inactivity--one study has shown that children who engage in the least amount of vigorous physical activity or the greatest amount of television viewing tend to be the most overweight. Playing computer games obviously compounds this serious problem.

Overweight children will likely become overweight adults. Adult obesity rates have more than doubled, from 15% to just over 30%, since the late 1970s, with the prevalence of obesity greater among women than men and also greater among Hispanic- and African-Americans than Caucasians. It also increases with age. Surveys of physical activity in 2000 indicate that 27% of US adults did not engage in any physical activity and another 28% were not regularly active.


Who's Overweight? Who's Obese? And How Does It Relate to Cancer Risk?

Studies examining body size and disease risk use a measure--body mass index (BMI: (weight in kilograms divided by height in meters squared)--to evaluate the impact of obesity on health outcomes. The World Health Organization (WHO) has established BMI categories that define overweight and obesity; these are shown in Table 1, which also includes popular descriptions of individuals in these categories and weight in pounds for individuals at two heights in inches (65 and 72 inches) that would place an individual at the upper limit of each category.

WHO = World Health Organization; BMI = body mass index weight in kg divided by height in m².

BMI is important because studies consistently show that as it increases, the risk of various malignancies--postmenopausal breast cancer, colon cancer (particularly among men), endometrial cancer, kidney cancer, esophageal adenocarcinoma--also increases. There's also growing evidence that physical inactivity is linked with increased endometrial cancer risk. The percentage of cancer incidence that can be attributed to being overweight or obese and to physical inactivity is shown in Table 2.

*BMI (body mass index) > 25 kg/m².

Colon Cancer
It's never too late to take the weight off when it comes to reducing colon cancer risk. Putting on excess weight earlier in life appears to be no more important than recent weight gain, suggesting that immediate weight reduction efforts could impact colon cancer risk. This is borne out by the fact that fairly recently begun physical activity practices have greater impact on colon cancer risk than activity during early adulthood. The greater impact obesity and overweight have on increased colon cancer risk for men may be due to the fact that the female hormone, estrogen, lowers women's risk. Women who use hormone replacement therapy have lower colon cancer risk. Overweight and obese postmenopausal women produce an estrogen through the reaction between an enzyme produced in body fat and the adrenal androgen, androstenedione, and thus, this aspect of being overweight could partly counteract other hazardous effects for women.

Breast Cancer
Obesity and weight gain during adult years are both associated with increased postmenopausal breast cancer risk. But, for premenopausal women, being heavy may reduce risk. These women may have menstrual cycle disturbances, which reduce their exposure to ovarian hormones (estradiol and progesterone) that are known to impact breast cancer risk. After menopause, when the ovaries no longer produce estrogen and progesterone, the enzymatic reaction in body fat converts androstenedione into an estrogen. Heavier women also produce less sex-hormone binding globulin, a protein that inactivates estrogen, resulting in higher levels of circulating estrogen. Obesity is also associated with increased insulin levels, which also may affect circulating hormone levels. Exercise may protect premenopausal women by reducing their exposure to ovarian hormones and may protect postmenopausal women by maintaining or lowering body weight in addition to exerting independent effects on estrogen levels.

Endometrial Cancer
Although obesity has been consistently associated with increased endometrial cancer risk, its impact may depend on age and menopausal status. Among premenopausal women, the effect may be restricted to the obese (>- 30 kg/m ²); among postmenopausal women, risk seems to increase linearly with increasing BMI. Endometrial cancer is a hormone-dependent cancer and estrogen therapy after menopause is a known cause of this cancer. Heavier postmenopausal women are thus exposed to excess levels of estrogen in the absence of progesterone, which ordinarily would counteract the effects of estrogen on endometrial tissue. Obesity and physical inactivity also increase insulin resistance, which appears to play a role in endometrial cancer development.

Esophageal Adenocarcinoma
An epidemic of esophageal adenocarcinoma, which was extremely rare 30 years ago, has paralleled the epidemic of obesity in developed countries; over the past 30 years, rate of this cancer has increased more that 350%. Studies have consistently indicated that obesity increases risk of this disease. Gastroesophageal reflux--common in obese patients--induces changes in the esophageal lining that lead to a condition called Barrett's esophagus, which is a precursor to cancer.

Other Cancers
Obesity increases kidney cancer risk, as do diabetes and hypertension, which are both obesity-related. The impact may be greater among women and it appears to be independent of blood pressure. While obesity does not seem to be an important risk factor for prostate cancer, physical activity may reduce risk. Two studies, one of men and the other of women, have shown that pancreatic risk is greatest among those who are obese and that, among those who are overweight or obese, physical activity appears to decrease risk.


Controlling Risk

In addition to cigarette smoking, obesity and physical inactivity may be the most important avoidable causes of cancer. Exercise can be an effective means for maintaining an ideal body weight or for reducing weight. It is important to encourage children to engage in regular exercise programs, as individuals who were active as children are more likely to be active as adults, whereas sedentary adults find it difficult to mount and then maintain an adequate exercise program.