Strong Association Increasingly Recognized Between Obesity and Cancer Incidence/Poor Prognosis


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The rise in obesity in the United States coincides with greater recognition of the role of obesity in cancer and other diseases.1 While decades of research have indicated a strong association between obesity and cancer, “several forces have made that association increasingly recognized,” according to Rachel Ballard-Barbash, MD, MPH, Associate Director of the Applied Research Program, Division of Cancer Control and Population Science, at the National Cancer Institute.

Convincing Evidence

Contributors to this greater recognition include “larger, better designed studies that have shown the association of obesity not just with the development of cancer, but also with adverse prognosis and shorter survival in people who have some types of cancer,” Dr. Ballard-Barbash told The ASCO Post. Other studies have resulted in greater understanding of the “underlying metabolic and physiologic characteristics that we think might contribute to cancer,” Dr. Ballard-Barbash said, and some intervention studies related to weight loss are showing positive results.

“The consistency of all of those factors combined have made people both more aware of the association between obesity and cancer and more confident that the association is real and not something that is confounded by another characteristic of people who are overweight or obese,” she said.

While the association between obesity and cancer is considered strong, it is not at the intensity level of smoking and lung cancer. “The relative risk for tobacoo use and lung cancer is maybe 14-fold or more. That was very strong association,” Dr. Ballard-Barbash explained. “The relative risk or odds ratio that we see for many of the obesity and cancer-related associations are more comparable to hypertension, heart disease, osteoporosis, and osteoarthritis, and physicians are very sure that those disorders are related to obesity,” she added.

Associated Cancers

According to the 2012 update of the American Cancer Society’s Cancer Facts & Figures,2 “overweight and obesity are clearly associated with increased risk for developing many cancers, including cancers of the breast in postmenopausal women, colon and rectum, endometrium, adenocarcinoma of the esophagus, kidney, and pancreas. Overweight and obesity may also be associated with increased risk of cancers of the liver, non-Hodgkin lymphoma, multiple myeloma, cervix, ovary, and aggressive prostate cancer, and obesity also likely increases the risk of cancer of the gallbladder. In addition, abdominal fatness is convincingly associated with colorectal cancer, and probably related to higher risk of pancreatic, endometrial, and postmenopausal breast cancers.”

Cancer Facts & Figures also notes that in the United States, “it has been estimated that overweight and obesity contribute to 14% to 20% of all cancer-related mortality.” That is the same estimate given in an article about obesity and cancer published in The New England Journal of Medicine in 2003.3 Based on a prospective study, the authors of that report noted that excess weight was implicated in deaths from endometrial cancer, adenocarcinoma of the esophagus, renal cancer, colon cancer, and postmenopausal breast cancer. Background material in the U.S. Preventive Services Task Force Recommendation Statement, Screening for and Management of Obesity in Adults,4 added that cancers of the liver and prostate are among the leading causes of death in obese adults.

“We are seeing a shift in the United States,” said Dr. Ballard-Barbash. “Early on, one of the more common causes for cirrhosis of the liver was due to alcohol or viral infections, like hepatitis. Today, we are seeing that obesity is becoming a more common cause of cirrhotic liver disease and that it is a major risk factor for liver cancer,” she explained.

“Most of the studies don’t find a very strong association between obesity and prostate cancer incidence, but there is some suggestion with more recent studies that obesity may be associated with more aggressive prostate cancer,” she continued. “And some studies among prostate cancer patients and survivors suggest that obesity may be associated with a greater risk of recurrence and poorer prognosis.”

More data now link obesity and pancreatic cancer, and “a number of studies have suggested that—particularly among women—being overweight or obese may increase the risk for some types of thyroid cancers,” Dr. Ballard-Barbash added. Possible associations between weight and some of the hematopoietic cancers are also being explored.

Screening for Obese Patients?

A study in Archives of Surgery5 found that obese patients present with more aggressive and advanced forms of papillary thyroid cancer and suggested that obese patients should be screened for thyroid cancer. Although obesity may increase the risk of thyroid cancer, “I do not believe that would be a rationale for initiating screening,” Dr. Ballard-Barbash said, noting that no groups currently recommend screening for thyroid cancer.

“It is particularly important that obese patients be screened for types of cancer we already routinely screen for, such as breast and colon cancers,” she said. “But we have evidence that obese patients tend to be less likely to undergo screening according to guidelines.” In addition, some forms of screening may not be as effective for obese patients. For example, breast cancer screening can be problematic in women with very large breasts associated with obesity.

‘Murky’ Recurrence Data

Obese women treated for breast cancer were more likely to have recurrences and inferior outcomes for overall survival, according to a study in the journal Cancer.6 The study evaluated the relationship between body mass index in three adjuvant breast cancer trials coordinated by the Eastern Cooperative Oncology Group (ECOG). The investigators reported, “obesity was associated with inferior outcomes specifically in patients with hormone receptor–positive operable breast cancer treated with standard chemohormonal therapy.”

In general, however, “we don’t currently have very good data on recurrence at the national level,” Dr. Ballard-Barbash said. “Outside of randomized controlled trials, where they are actively ascertaining whether people have recurrence on an ongoing basis, our cancer registry data is very murky in terms of capturing recurrence. It captures new breast primaries and deaths very well, but it doesn’t capture recurrence.”

Benefits of Physical Activity

Several published studies have suggested that patients with cancer who regularly engage in physical activity “may experience better survival,” Dr. Ballard-Barbash said. “I just published a review in the Journal of the National Cancer Institute7 this year, summarizing the data from a number of observational studies on how physical activity is associated with cancer survival,” she said. That review about physical activity and breast cancer, described in a previous article in The ASCO Post,8 found “consistent evidence” that physical activity is associated with reduced mortality from breast cancer.

Although there have been randomized controlled trials demonstrating that physical activity can improve quality of life for patients with cancer, there have not yet been randomized controlled trials demonstrating improved survival, Dr. Barbash-Ballard noted. So physicians may be hesitant to tell patients, “you definitely will do better in terms of survival if you control your weight or are physically active.” Several randomized controlled trials have been designed to understand how physical activity can impact cancer recurrence and survival, Dr. Ballard-Barbash said, but these trials are still enrolling patients and have not yet reported results.

Patients undergoing cancer treatment may find it challenging to stay physically active, Dr. Ballard-Barbash acknowledged, “but a number of studies have shown that it is possible to help people initiate a physical activity program even during active treatment” and that as a result, quality of life is improved, she said. “In fact, there is some evidence that they are better able to tolerate a full dose of chemotherapy,” she added.

The benefits of physical activity can come from the activity itself and its effect on weight reduction. “I don’t think we know for sure,” Dr. Ballard-Barbash said. “The studies have been a little bit inconsistent. A few studies have demonstrated that the reduced risk for women who are physically active is found predominantly in those of normal weight, suggesting that a major mechanism in breast cancer may be related to reduction in fat mass. Other studies have found the benefit even among women who are overweight. And some studies in colorectal cancer have shown a benefit of physical activity across all body mass index categories. So it varies somewhat by cancer site,” she added.

“There is no question that reduction of fat mass is one mechanism by which physical activity may be beneficial, but there are many other mechanisms being examined, including improvements in insulin, glucose metabolism, and reductions in inflammation,” she continued. “Inflammation may increase risk for cancer as well as be associated with worse prognoses. So there are multiple mechanisms by which physical activity may be operating.”

Role of High Birth Weight

“A limited number of studies indicate that birth weight may be associated with cancer risk,” Dr. Ballard-Barbash said. “For many years, studies have suggested that babies with a very low birth weight are at increased risk for heart disease and diabetes.” For some cancers, however, studies have found an increased risk for babies with high birth weights. “That has been shown, for example, in breast cancer,” Dr. Ballard-Barbash said. Studies have also shown associations between high birth weight and testicular, brain, and some hematologic cancers. ■

Disclosure: Dr. Ballard-Barbash reported no potential conflicts of interest.

References

1. Trust for America’s Health/Robert Wood Johnson Foundation: F as in fat: How obesity threatens America’s future. September 2012. Available at www.healthyamericans.org/report/100. Accessed October 17, 2012.

2. American Cancer Society: Cancer facts & figures 2012. Available at www.cancer.org. Accessed October 17, 2012.

3. Calle EE, Rodriguez C, Walker-Thurmond K, et al: Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 348:1625-1638, 2003.

4. Moyer VA, on behalf of the U.S. Preventive Services Task Force: Screening for and management of obesity in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 157:373-378, 2012.

5. Harari A, Endo B, Nishimoto S, et al: Risk of advanced papillary thyroid cancer in obese patients. Arch Surg 147:805-811, 2012.

6. Sparano JA, Wang M, Zhao F, et al: Obesity at diagnosis is associated with inferior outcomes in hormone receptor-positive operable breast cancer. Cancer. August 27, 2012 (early release online).

7. Ballard-Barbash R, Friedenreich CM, Courneya KS, et al: Physical activity, biomarkers, and disease outcomes in cancer survivors: A systematic review. J Natl Cancer Inst 104:815-840, 2012.

8. Bath C: Physical activity benefits breast cancer survivors, but role in reducing breast cancer risk is less clear. The ASCO Post, September 15, 2012.


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