Reducing Cancer Risk

We Can't Breathe Easy Yet

Breast and Ovarian Cancer Prevention in High-Risk Women

The Anticancer Properties of Selective COX-2 Inhibitors

Radical Prostatectomy and its Impact on the Effectiveness of Screening for Prostate Cancer

Patient Selection for Breast Cancer Screening

News from the NCI

Issues & Insights

Cancer Prevention Clinical Trials

Cancer Prevention Legislation (Federal)

Cancer Prevention Legislation (State)

Make Your Voice Heard

Other Information Resources

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, and thus represents a major public health burden. Regular physical activity helps avoid weight gain and independently may reduce the risk of these diseases.

Obesity rates have been increasing dramatically for more than 20 years in the US and other westernized countries, amounting, in fact, to an epidemic.(1) During this period, the percentage of overweight adolescents in the US increased more than 3-fold, from 4.6% to 15.5%, and the percentage of younger children, ages 6-11 years, increased from 5% to 15.3%(2) Physical inactivity has contributed to this epidemic. One US 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.(3) Computer usage obviously compounds this problem.

Overweight children will likely become overweight adults. Among US adults, 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, greater among Hispanics and African-Americans than whites, and also increasing with age.(4-5) The prevalence of individuals in the overweight category has remained relatively constant during this time. 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.(6)

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 (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). (1)

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

Studies consistently show that, as BMI increases, the risks of postmenopausal breast cancer, colon cancer (particularly among men), endometrial cancer, kidney cancer, and esophageal adenocarcinoma also increase. Individuals with a physically active lifestyle have reduced risks of breast and colon cancer; evidence is accumulating that physical inactivity is also associated 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.(1) Overweight and obesity account for 39% of endometrial cancers, 37% of esophageal cancers, and about 10% of colon and breast cancer. Recent results from the American Cancer Society cohort of more than 900,000 US men and women who were followed for 16 years indicate that among nonsmokers, overweight and obesity account for 14% of all cancer deaths among men and 20% of all cancer deaths among women.(7) Estimates indicate that physical inactivity accounts for 11% of breast cancer and 13% to14% of colon cancer incidence.(1) The data also suggest that physical inactivity may account for about 11% of endometrial cancers.

*BMI (body mass index) > 25 kg/m^2.

The adverse impact of overweight and obesity on colon cancer risk is stronger for the distal than for the proximal colon and stronger among men.(1) A possible explanation for this gender difference is that hormone replacement therapy appears to reduce women's colon cancer risk. This protection may also apply to endogenous estrogen that overweight and obese postmenopausal women produce through the reaction between an enzyme produced in body fat and the adrenal androgen, androstenedione. Weight earlier in life appears to be no more important than recent weight, suggesting that immediate weight reduction efforts could impact colon cancer risk. This is borne out by the fact that fairly recent physical activity practices have greater impact on colon cancer risk than activity during early adulthood. However, neither BMI nor physical activity appears to impact rectal cancer risk. Several mechanisms have been proposed to explain the relationships of obesity and inactivity to colon cancer risk, including alterations in prostaglandin activity and insulin sensitivity, changes in growth factor profiles, and a decrease in stool transit time through the colon.

Obesity and weight gain during adult years are both associated with increased postmenopausal breast cancer risk; risk is not increased in premenopausal women.(1) In fact, being heavy may reduce the breast cancer risk for this group. 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 estrone. 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 an increase in insulin levels, which also may impact circulating hormone levels. Exercise activity has been studied extensively in relation to breast cancer risk, with many large case-control and cohort studies finding protective effects. Exercise activity may protect premenopausal women by reducing exposure to ovarian hormones and protect postmenopausal women by maintaining or lowering body weight in addition to exerting independent effects on estrogen levels.

Adult obesity has been consistently associated with increased endometrial cancer risk; nevertheless, the impact of obesity may depend on age and menopausal status. Among premenopausal women, the effect may be restricted to those in the obese category (>= 30 kg/m²); 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. Thus, it is not surprising that obesity is associated with greater risk of endometrial cancer, particularly among postmenopausal women, for the reasons cited above in relation to breast cancer. Heavier postmenopausal women are exposed to excess levels of estrogen in the absence of progesterone, which would counteract the proliferative effects of estrogen on endometrial tissue. Obesity and physical inactivity also increase insulin resistance, which appears to play a role in endometrial cancer development.

An epidemic of esophageal adenocarcinoma, which was extremely rare 30 years ago, has paralleled the epidemic of obesity in developed countries.(1) Over the past 30 years, rates of esophageal adenocarcinoma have 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 epithelium that lead to Barrett's esophagus (a lesion of columnar cells in the squamous cell lined esophagus), which is a precursor to cancer. The impact of physical activity on this cancer has not been studied.

Obesity increases kidney cancer risk, as do diabetes and hypertension, which are both obesity-related.(1) The impact may be greater among women and it appears to be independent of blood pressure. The few studies of physical activity in relation to kidney cancer risk that have been conducted provide no conclusive results.

Obesity does not seem to be an important predictor of prostate cancer development, yet physical activity may reduce risk.(1) Although little information is available on risk factors for pancreatic cancer, two cohort 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(8). Further studies of this relationship are needed.

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.

References

1. International Agency for Research on Cancer. IARC Handbooks of Cancer Prevention, Volume 6. Weight Control and Physical Activity. Lyon, France: IARC Press, 2002.
2. Ogden CL, Flegal KM, Carroll MD, et al. Prevalence and trends in overweight among US children and adolescents, 1999-2000. JAMA. 2002;288:1728-1732.
3. Andersen RE, Crespo CJ, Bartlett SJ, et al. Relationship of physical activity and television watching with body weight and level of fatness among children: results from the Third National Health and Nutrition Examination Survey. JAMA. 1998;279:938-942.
4. Flegal KM, Carroll MD, Kuczmarski RJ, et al. Overweight and obesity in the United States: prevalence and trends, 1960-1994. Int J Obes Rel Metab Disord. 1998;22:39-47.
5. Flegal KM, Carroll MD, Ogden CL, et al. Prevalence and trends in obesity among US adults 1999-2000. JAMA. 2002;288:1723-1727.
6. Mokdad AH, Bowman BA, Ford ES, et al. The continuing epidemics of obesity and diabetes in the United States. JAMA. 2001;296:1195-1200.
7. Calle EE, Rodriguez C, Walker-Thurmond K, et al. Overweight, obesity and mortality from cancer in a prospectively studied cohort of U.S. adults. New Engl J Med. 2003;348:1625-1638.
8. Michaud DS, Giovannucci E, Willett WC, et al. Physical activity, obesity, height and the risk of pancreatic cancer. JAMA. 2001;286:921-929.