1 / 41

The Weight of the Issue: Obesity and Cancer

The Weight of the Issue: Obesity and Cancer. Blakely Kute , MD Hematology and Oncology Fellow February 3, 2011. Obesity and Cancer. Associated with wide range of cancer types Varying mechanisms of inducing tumorigenesis Hyperinsulinemia Inflammation

Download Presentation

The Weight of the Issue: Obesity and Cancer

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. The Weight of the Issue:Obesity and Cancer Blakely Kute, MD Hematology and Oncology Fellow February 3, 2011

  2. Obesity and Cancer • Associated with wide range of cancer types • Varying mechanisms of inducing tumorigenesis • Hyperinsulinemia • Inflammation • Increased bioavailability of steroid hormones [1]

  3. Obesity Trends* Among U.S. AdultsBRFSS,1990, 1999, 2009 (*BMI 30, or about 30 lbs. overweight for 5’4” person) 1999 1990 2009 No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30% http://www.cdc.gov/obesity/data/trends.html

  4. Measuring Adiposity • Ideally include both subcutaneous and visceral • Methods: • Hydrodensitometry • Skin folds • Waist circumference • DEXA • CT • MRI

  5. Measuring Adiposity • Body Mass Index • Most cost effective • Highly specific, but poor sensitivity • BMI > 30 failed to reveal 50% of people with excess body fat • Less sensitive in elderly – shift of peripheral fat to central • “Normal weight obesity” • Abdominal obesity • at risk for : • metabolic syndrome • hyperlipidemia • cardiovascular disease

  6. Obesity and Cancer Connection • 1970s: adiposity contributes to increased incidence and/or death from: • Colon cancer • Gallbladder cancer • Liver cancer • Pancreatic cancer • Gastroesophageal cancer • Breast cancer (post menopausal) • Endometrial cancer • Kidney (renal cell) cancer

  7. Overweight/Obesity Burden • Total health burden of obesity and overweight may exceed cigarette smoking • Past 15 years: • Smoking rates ↓ 20% • Obesity rates ↑ 48% • Life expectancy projected to continue to rise, but more slowly secondary to increasing obesity.

  8. Obesity and Cancer Incidence • IARC estimates that obesity causes: • 11% of colon cancer cases • 9% of postmenopausal breast cancer cases • 39% of endometrial cancer cases • 25% of kidney cancer cases • 37% of esophageal cancer cases

  9. Obesity and Cancer Incidence

  10. Obesity and Cancer Mortality Connection • 1970s: • 15-20% of cancer deaths attributed to overweight and obesity • 2000s: • Still attributing 14-20% of cancer deaths to obesity and overweight • BMI > 40 associated with 52% (men) and 62 % (women) higher death rates from all cancers combined Callie EE. Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N. Engl. J. Med. 2003; 348: 1625-1638.

  11. Characterizing the association • Cancer Prevention Study II • Prospective mortality study begun by the ACS in 1982. • 1,184,617 participants • Volunteer enrollment • Completion of a confidential mailed questionnaire • Report of deaths before 1988 were from personal inquires. After 1988, reports were from the National Death Index. • Subset analysis used for weight association with increased risk of death from cancer

  12. Applying the Data from Cancer Prevention Study • Baseline questionnaire – • asked current weight, weight one year previously, and height (without shoes) • Callie et al with ACS, 2003 • Subset analysis on the influence of excess body weight on the risk of death from cancer • Study Exclusions: • if you didn’t know your weight or had lost more than 10 lbs within the previous year • BMI <18.5 • previous cancer history, with the exception of non-melanoma skin cancer • if you excluded smoking or race history

  13. Applying the Data from Cancer Prevention Study II • Subset analysis from Callie et al, 2003 studying weight on cancer mortality • 404,576 men • 495,477 women • Average age 57 • 16 year follow up: • 32,303 deaths from cancer in men • 24,842 cancer deaths in women • End points: deaths from all cancers and deaths from specific sites

  14. Applying the Data from Cancer Prevention Study II • Callie et al also defined subset of non-smokers • 107,030 men • 276,564 women • Cancer deaths among non-smokers: • 5,314 deaths among men • 11,648 deaths among women • End points: deaths from all cancers and deaths from specific sites • Allowed the investigators to evaluate whether the association between BMI and mortality was subject to residual confounding by smoking status for smoking related cancers.

  15. More results • Proportion of cancer deaths attributable to overweight and obesity: • Men: 4.2 to 14.2 percent • Women: 14.3 to 19.8 percent • Lower risks based on entire population studied • Higher risks based on nonsmoking population • Potentially, more than 90,000 US deaths from cancer might be avoided if adults could maintain BMI under 25.0 throughout life

  16. Abdominal Obesity • Definition: • ≥ 88 cm in women and ≥ 102 cm in mne • Incidence: • ≥ 70% of women and ≥ 50% of men aged 50-79 years • Importance • Visceral adipocytes: • more metabolically active • high lipolytic activity • release large amounts fatty acids • Increases incidence of (independent of BMI): • Pancreatic, endometrial and postmenopausal breast cancer

  17. Abdominal Obesity • Weight circumference subset of Cancer Prevention Study II • Correlated independently of BMI with: • elevated inflammatory markers • type 2 diabetes and insulin resistance • Dyslipidemia • Increasing waist circumference associated with progressively higher risk of all cause mortality in men and women (after adjustment for BMI)

  18. Proposed mechanisms • Adipose tissue constitutes an active endocrine and metabolic organ resulting in: • Chronic hyperinsulinemia • Elevated endogenous sex steroids • Chronic inflammation • Non-alcoholic fatty liver disease • Increased incidence of GERD • ?? Vit D deficiency

  19. Proposed mechanisms

  20. Chronic Hyperinsulinemia • Associated with colon, breast, pancreatic, and endometrial cancers • Tumorigenic effects: • Directly mediated from receptors on (pre)neoplastic cells • Indirectly via changes in hormone metabolism • Androgens, estrogens, progesterone, IGF-1 and its binding proteins

  21. Increased Endogenous Steroids • Associated with endometrial and post-menopausal breast cancer

  22. Endometrial cancer • Most closely linked cancer with obesity and overweight

  23. Chronic Inflammation • Associated with: • Multiple Myeloma • Non-Hodgkin’s lymphoma • Liver • Increased TNF-alpha, IL-6 and STAT3

  24. Colon cancer • Obese men more likely than obese females to develop colon cancer • Theories: • Abdominal obesity, more prevalent in men, is a greater risk factor than peripheral fat • Offsetting beneficial effect of obesity from elevated endogenous hormones • Theory based on decreased rates of CRC in women on postmenopausal hormone therapy • Highly associated with increased insulin levels

  25. Post-menopausal Breast Cancer • Obesity may increase rates 30-50% • Adult weight gain associated with ↑ risk • Obesity associated with increased likelihood of recurrence, regardless of menopausal status, after adjustment for stage/treatment • “Very obese” (BMI > 40) have death rates 3X higher than “very lean” (BMI <20.5) • Some theories regarding delayed diagnosis in obese patients

  26. Specific cancers • Endometrial cancer • 1st cancer to be found to be related to obesity • Direct relationship • 2-3.5-fold increase in risk of incidence • Renal Cell carcinoma • Association of obesity seems to be independent of hypertension

  27. Specific cancers • Esophageal, adenocarcinoma • Indirectly via increased reflux • Proposed direct mechanism too • Hepatocellular cancer • Likely related to the spectrum of NASH -> cirrhosis-> HCC • Gallbladder • Not shown to be consistently related, but related to increased risk of gallstones -> chronic inflammation

  28. Specific cancers • Lung cancer • Inversely associated • Theory: Smoking is primary cause of lung cancer and smoking is inversely related to BMI • Prostate cancer • No firm relationship, but suggestion • Likely related to hyperinsulinemia • More likely to have aggressive disease that recurs

  29. Specific cancers • Ovarian cancer • No firmly established link • May be some increased link to certain pathologies (endometrioid) • Cervical cancer • Not enough data to confirm link • Several studies showing decreased compliance with PAP smears with increasing body weight

  30. Additional complications of obesity • Dosing chemotherapy • Actual verses adjusted BSA • Potential for difficulty with radiation dosimetry and higher rate of complications • Increased surgical complications: • Increased OR time, impaired respirations, difficult intubations, poor exposure to operative field, increased blood loss • Postoperative complications: increased risk for DVT, poor wound healing, and pulmonary complications

  31. Can weight loss help? • Bariatric surgery population studied • Varying results • Mean weight loss 14-27%in US and Swedish group showed up to 38% lower cancer death rates • Decrease in post-menopausal breast ca rates • Other studies do not demonstrate such effects • Weight loss after menopause significantly decreases breast cancer risk

  32. Is extra weight ever helpful • Surgical studies • Protective in premenopausal breast cancer • BMI >28

  33. Implications on Kentucky 1. Mississippi 33.8% 2. Alabama 31.6%3. Tennessee 31.6%4. West Virginia 31.3% 5. Louisiana 31.2%6. Oklahoma 30.6%7. Kentucky 30.5% 8. Arkansas 30.1%9. South Carolina 29.9%10. North Carolina 29.4% 10. Michigan 29.4% 12. Missouri 29.3% 13. Ohio 29.0% 13. Texas 29.0% 15. South Dakota 28.5% 16. Kansas 28.2% 17. Pennsylvania 28.1% 17. Georgia 28.1% 17. Indiana 28.1% 2010 Obesity Rates

  34. 2009 Obesity Data No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

  35. Implications on Kentucky • Education and Prevention are key • 2009 KY started school nutrition programs • Do not have mandate regarding school physical activity • Louisville had Health Promotion Schools of Excellence • Better BMI documentation and obesity discussions • UK study showed only 61% of patients in a large primary health care group had BMI documented • Those with high BMIs had poorer control of HTN, HLD, and glucose than did their normal BMI counterparts

  36. References • Calle EE and R Kaaks. Overweight, Obesity and Cancer: Epidemiological Evidence and Proposed Mechanisms. Nat Rev Cancer 2004. 4(8). • http://www.cdc.gov/obesity/data/trends.html • Okorodudu DO, Jumean MF, Montori VM, Romero-Corral A, Somers VK, Erwin PJ, Lopez-Jimenez F. Diagnostic performance of body mass index to identify obesity as defined by body adiposity: a systematic review and meta-analysis. Int J Obes 2001; 34(5):791-799. • Romero-Corral A, Somers VK, Sierra-Johnson J, Korenfeld Y, Boarin S, Korinek J, Jensen MD, Parati G, Lopez-Jimenez F. Normal weight obesity: a risk factor for cardiometabolic dysregulation and cardiovascular mortality. Eur Heart J. 2010; 31(6):737-746. • Callie EE. Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N. Engl. J. Med. 2003; 348: 1625-1638. • Wolin KY, Carson K, Colditz GA. Obesity and Cancer. The Oncologist 2010; 15:556-565. • Stewart ST, Cutler DM, Rosen AB. Forecasting the effects of obestiy and smoking on U.S. life expectancy. N Engl J Med 2009; 361:2252-2260. • International Agency for Research on Cancer. Weight Control and Physical Activity, Volume 6, Lyon: International Agency for Research on Cancer, 2002:1-315. • Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008;371:569-578. • Jacobs EJ, Newton CC, Wang Y, Patel AV, McCullough ML, Campbell PI, Thun MJ, Gapstar SM. Waist Circumference and All-Cause Mortality in a Large US Cohort. Arch Intern Med 2010; 170:1293-1301. • Langunova Z, Porojnicu AC. Grant WB, Bruland O, Moan JE. Obesity and increased risk of cancer: Does decrease of serum 25-hydroxyvitamin D level with increasing body mass explain some of the association? Mol. Nutr. Food Res. 2010;54:1127-1133. • Modesitt SC and vanNagell JR. The Impact of Obesity on the Incidence and Treatment of Gynecologic Cancers: A Review. Obstetrical and Gynelogical Survey 2005; 60(10):683-692. • Msnbc.com • http://www.statehealthfacts.org/profileind.jsp?ind=52&cat=2&rgn=19 • http://www.ket.org/commonhealth/models/healthpromo.htm

More Related