Obesity and Cancer

May 15th, 2012 by MorganDowney Leave a reply »

I testified last week at the FDA AdCom on lorcaserin. I prepared my testimony to talk about cancer in humans, rather than cancer in rats, which I knew would be the topic of the meeting. I didn’t deliver all of the following testimony. I only had about 4 minutes so I go through about half.

M. Downey Prepared statement before Endocrinologic and Metabolic Advisory Committee on lorcaserin, May 10, 2010.

Mr. Chairman, thank you for this opportunity to appear before the Advisory Committee. I have no financial relationship with the sponsor and no one paid for my participation at this hearing.

This morning we learned a lot about tumors in rats. Thank you. I learned a lot. Over several years, the committee has discussed the health effects of obesity but I do not recall many discussions about the effects of obesity on human cancer. I have three quick points:

  • Obesity/low physical activity is associated with increased risk of cancer in both men and women

  • Mechanisms of action in different cancers is unknown

  • Weight management appears useful for cancer survivors

Mortality

One study, using NCI Surveillance, Epidemiology, and End Results (SEER) data, estimated that in 2007 in the United States, about 34,000 new cases of cancer in men (4 percent) and 50,500 in women (7 percent) were due to obesity. Recent studies indicate that obesity and being overweight may increase the risk of death from many cancers, accounting for up to 14 percent of cancer deaths in men and 20 percent of cancer deaths in women. NCI:Fact Sheet:Obesity

Epidemiology

Not only is obesity increasing, the normal weight population is totally collapsing. This is an unique change in human physiology.

This is the graph of changes in the US from 1971 to 2008.

However, new projections show that in two decades, the overweight/obese population will increase by 33% and the severe/morbidly obese population will increase by a staggering 138%, according to a new publication by Finkelstein and colleagues at RTI and CDC. AJPM:Finkelstein:Projections_2030

According to the Annual Report to the Nation on the Status of Cancer:

  • Considerable evidence suggests that excess weight may be associated with increased risk of other cancers, including gallbladder, liver, thyroid, and hematopoietic cancers.

  • Lack of physical activity is associated with increased risk of colon, endometrial and postmenopausal and maybe premenopausal breast cancer.

    Excess weight is associated with poorer survival among patients with breast cancer and colorectal cancer.” Eheman C, et al Annual Report to the Nation on the Status of Cancer, 1975-2008, Cancer 2012 May 1;118(9):2338-66

The connection between obesity and cancer have been attributed to:

  • Hormones

  • Growth Factors

  • Inflammation

However, no definitive path of causality has been established.

A study by Ma and colleagues has found starkly increased death rates due to cancer, as well as cardiovascular disease, in a large cohort of 112,000  Americans aged 18-39, followed for 16 years.  Ma J, et al,

But obesity does not appear to have a blanket effect on all types of cancers, nor to affect cancer risk the same in men and women. One study found that obesity increases the risk of dying from all cancers by about 52% in men, but nearly doubled the risk of dying from any type of cancer in women.” PubMed:Calle_2003

In 2011, the Institute of Medicine National Cancer Policy Forum held a workshop on the impact of obesity on cancer survivorship, the general trend of the dialogue was that:

  • It is still an open question on recommending and implementing weight loss among cancer survivors

  • But sufficient evidence of general benefit of lower weight on health and increased risk of recurrence with obesity

  • Practical problems of cancers survivors attempting to lose weight.

Current research:

  • Imayama et al examined the effects of diet and exercise on inflammatory biomarkers in 439 postmenopausal women. The women were randomized to 1 year of caloric restriction diet, aerobic exercise or combined diet and exercise. Women in the diet and diet + exercise group with a 5% or more weight loss reduced inflammatory biomarkers compared with controls. The diet only and diet plus exercise groups showed reductions. Inflammation has been hypothesized to be a mechanism for cancer in obese patients. Cancer Research : Effect of Caloric Restriction

    • Last year, the same research team found that a combined diet and exercise intervention had positive effects on health related quality of life (HRQOL) in overweigh/obese postmenopausal women. Weight loss predicted improvements in physical functioning, vitality and mental health. Improved HRQOL led to positive changes in depression, stress and social support. PubMed: Dietary weight loss and exercise effect on HRQOL

    • A study published last November showed that a high body mass index BMI) at the time of diagnosis of breast cancer is associated with higher mortality, as is weight gain at later times. A low-fat diet rich in fruit, vegetables and fiber seems to be weakly associated with a better prognosis. There was no evidence of any benefit from micronutrients, supplements or antioxidant foods. Alcohol consumption did not affect outcomes in breast cancer. PubMed: Effect of overweight on breast cancer prognosis

    • Early stage overweight and obese endometrial cancer survivors randomized to 6 month lifestyle intervention or usual care. Adherence was 84%. Difference in weight at six months was -4.4kg and -4.6 at 12 months conclusion, behavior change and weight loss are achievable but clinical implications unclear. PubMed: Survivors of Uterine Cancer, SUCCEED Trial

    • A study published last November showed that a high body mass index BMI) at the time of diagnosis of breast cancer is associated with higher mortality, as is weight gain at later times. A low-fat diet rich in fruit, vegetables and fiber seems to be weakly associated with a better prognosis. There was no evidence of any benefit from micronutrients, supplements or antioxidant foods. Alcohol consumption did not affect outcomes in breast cancer. PubMed: Effect of overweight on breast cancer prognosis

    • Early stage overweight and obese endometrial cancer survivors randomized to 6 month lifestyle intervention or usual care. Adherence was 84%. Difference in weight at six months was -4.4kg and -4.6 at 12 months conclusion, behavior change and weight loss are achievable but clinical implications unclear. PubMed: Survivors of Uterine Cancer, SUCCEED Trial

    • A study published last November showed that a high body mass index BMI) at the time of diagnosis of breast cancer is associated with higher mortality, as is weight gain at later times. A low-fat diet rich in fruit, vegetables and fiber seems to be weakly associated with a better prognosis. There was no evidence of any benefit from micronutrients, supplements or antioxidant foods. Alcohol consumption did not affect outcomes in breast cancer. Hauner D, et al, The effect of overweight and nutrition on prognosis in breast cancer. Dtsch Arztebl Intl 2011 Nov. 108(47):795-801/ PubMed: Effect of overweight on breast cancer prognosis

    • Early stage overweight and obese endometrial cancer survivors randomized to 6 month lifestyle intervention or usual care. Adherence was 84%. Difference in weight at six months was -4.4kg and -4.6 at 12 months conclusion, behavior change and weight loss are achievable but clinical implications unclear. Von Gruenigen V et al, Survivors of uterine cancer empowered by exercise and healthy diet (SUCCEES): A randomized controlled trial, Gyneco Oncol 2012 Mar 28 PubMed: Survivors of Uterine Cancer, SUCCEED Trial

 

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