BODY FAT AND CANCER
HOW DO WE MEASURE OBESITY:
In the United States the majority of adults over 20 years of age have a percent body fat that increases their risk for metabolic diseases [NHANES Results CDC and NCHS No.237.March 2016]. The definition of obesity is based on a measure called BMI – body mass index-your weight in kilograms divided by your height in meters squared. This measure is not precise since it does not distinguish lean body mass from fat body mass. For most people however, BMI can be used as a measure of relative health as follows:
In 2012 one out of three people in the United States were not just over weight but objectively obese [C.L. Ogden et al; NCHS brief no. 131; 2013]. In morbidly obese people [BMI>40] the death rates from all cancers combined are 52 percent higher for men and 62 percent higher for women when compared with the rates in men and women of normal weight [E E Calle et al; N Eng J Med 2003; 348; 1625-1638]. Thus there is a strong link between cancer and obesity.
CANCER AND OBESITY
Obesity is associated with an increased risk of many cancers.
Below is a list of known malignancies associated with obesity.
- COLON AND RECTUM
- POST MENOPAUSAL BREAST
INCREASE BREAST CANCER RISK
The data showing an increased risk of breast cancer in the obese is epidemiologic and is found in the Nurses Health Study initiated by Dr. Frank Speizer in 1976. What is known is that weight gain after menopause, increases the risk of breast cancer among postmenopausal women while weight loss after menopause is associated with a decreased risk of breast cancer. Gaining 22 lbs after menopause increased the risk of developing breast cancer by 18% [A.H. Eliassen et al; JAMA 2006; 296(2); 193-201]. In addition obese women with breast cancer have larger breast primary cancers, greater lymph node involvement, and a 30 % greater risk of breast cancer mortality than non-obese women [M. Protani et al; 2010; Breast Cancer Res Treat 123(3); 627–635].
HOW FAT CAUSES SPECIFIC CANCERS
The reasons fat cells cause specific cancers are currently under study. What is known is that fat cells produce chemical messengers or “adipokines” that communicate with other cells. These adipokines are similar to hormones or ligands and cause other cells to produce products or proteins that alter cell function.
Leptin One adipokine [product of fat cells] is called leptin. Leptin is produced by fat cells and the leptin blood level is proportional to fat cell mass. Leptin inhibits hunger and likely does much more. High levels of leptin are associated with a higher risk of breast cancer even after adjustment for obesity suggesting an independent role for leptin in the development of breast cancer [M-H Wu et al; B J Cancer 100; 2009; 578-582]. In estrogen receptor positive breast cancer cells leptin simulates DNA synthesis and acts as a tumor growth factor [C Garofalo and E Surmacz; J Cellular Physiology 207(1); 2006; 12-22]. Leptin is also implicated in prostate cancer. Leptin stimulates prostate growth, angiogenesis, and increased leptin levels are a risk factor for prostate cancer [P.Stattin et al; J Clin Endo Metab 86(3); 2000].
Resistin in humans is a product of fat cells [adipokine] and is associated with “insulin resistance”. Resistin increases the production of many molecules associated with “inflammation”. Inflammation is the activation of the bodies immune system including white blood cells and their cellular products- IL-1, IL-6, IL-12, TNF, and other “cytokines”-products of inflammatory cells. High resistin expression in breast cancer tissue is associated with a more aggressive disease and poor patient survival. High resistin predicts a poor prognosis [Y.C. Lee et al; Gynecol Oncol 2012; 125 (3); 742-750].
In postmenopausal women with high body fat there is a significant increase in estrogen production with increasing BMI [M.P.Cleary and M.P.Grossmann; Endocrinology 150(6); 2009 ]. In these obese postmenopausal women adipose tissue is the main source of estrogen biosynthesis. This is due to the presence of aromatase in fat cells whose primary job is to synthesize estrogens. Fat cells produce additional aromatase enhancing ligands-TNF alpha and IL-6. Thus high tissue estrogen levels can be found in the fatty tissues of the breast and in breast tumors [ A.A. Van Landeghem et al; Cancer Res 45; 1985; 2907-2912]. High estrogen levels increase breast cancer risk [L.Bernstein and R.K.Ross; 1993; Epidemiol Rev 15; 48-65].
COLON CANCER AND RECTAL CANCER
A meta-analysis of 30 prospective studies reveals an increased risk of colon cancer and rectal cancer in obese men. A five unit increase in BMI increases the risk of colon cancer and rectal cancer significantly. A ten cm increase in waist size also increases the colon cancer risk in men [S.C.Larsson and A.Wolk; 2007; AM J Clin Nutr 86(3); 556-565].
Obesity and the products of fat cells –adipokines-play a role in promoting the progression of established prostate cancer. The precise molecular sequence of events is not completely understood. What is known is that high levels of leptin, interleukin 6 [IL-6], and VEGF are associated with increased prostate cancer risk and increased aggressiveness. Adipokines exert a variety of biologic effects on prostate cancer cells, modulating cellular differentiation, apoptosis, proliferation, and angiogenesis [T.Mistry et al; European Urology 2007; 52(1); 46-53]. In prostate cancer IL-6 causes tumor growth through activation of the androgen receptor [K.Malinowska et al; Endocr Relat Cancer 2009; 16(1); 155-169]. In addition high TNF level increase the tumor cell survival and metastasis potential in many different cancers (F.Balkwill;Semin Cancer Biol 2004; 14(3); 155-169].
Today we know that adipose tissue is not just a storage site for energy. Adipose tissue produces many polypeptide growth factors and cytokines, known as adipokines. Fat cells form a metabolically active organ that plays an active role in cellular metabolism, energy balance, immunity, hormone production, and cancer risk.