Body Weight

• “Fat cells may absorb and break down common chemotherapy drugs, reducing their potency…This finding may help explain why obesity is linked to poorer outcomes in several types of cancer.”¹Obesity and cancer: Increasing risks, complicating treatments. Cancer Treatment Centers of America. February 8, 2021. Viewed September 21, 2021.

• Earlier cancer relapse (shorter time to progression) among people with metastatic colorectal cancer with fatigue and weight loss related to chemotherapy compared to those without fatigue and weight loss in a mid-sized observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study²Innominato PF, Giacchetti S et al. Fatigue and weight loss predict survival on circadian chemotherapy for metastatic colorectal cancer. Cancer. 2013 Jul 15;119(14):2564-73.

• Shorter survival among people with high-grade glioma who were either underweight (BMI less than 18.5) or obese (BMI more than 30) compared to normal BMI (between 18.5 and 29.9) during 1-5 years prior to the study interview in a large observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study³Siegel EM, Nabors LB et al. Prediagnostic body weight and survival in high grade glioma. Journal of Neuro-oncology. 2013 Aug;114(1):79-84.
• A link between increasing BMI and worse survival among people with high-grade glioma in a mid-sized observational study⁴Chambless LB, Parker SL, Hassam-Malani L, McGirt MJ, Thompson RC. Type 2 diabetes mellitus and obesity are independent risk factors for poor outcome in patients with high-grade glioma. Journal of Neuro-oncology. 2012 Jan;106(2):383-9.

• No link between mortality from breast cancer diagnosed before menopause and body mass index (BMI) in a very large meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 126 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies⁵Chan DSM, Abar L et al. World Cancer Research Fund International: Continuous Update Project-systematic literature review and meta-analysis of observational cohort studies on physical activity, sedentary behavior, adiposity, and weight change and breast cancer risk. Cancer Causes & Control. 2019 Nov;30(11):1183-1200.
• Lowest risk of overall mortality among women with breast cancer who kept their weight stable in the first few years after diagnosis, while more than 10% weight gain or loss was linked to higher mortality; excessive weight loss after diagnosis of breast cancer, especially in patients with other chronic illnesses such as cardiovascular disease, was associated with reduced overall survival—patients were more likely to die from one of the other chronic illnesses than from cancer in a very large observational study⁶Caan BJ, Kwan ML et al. Weight change and survival after breast cancer in the After Breast Cancer Pooling Project. Cancer Epidemiology, Biomarkers & Prevention. 2012 Aug;21(8):1260-71.
• 13% increase in breast cancer-specific mortality with each 5 BMI units, such as a BMI change from 25 to 30, of weight gain after diagnosis⁷Nichols HB, Trentham-Dietz A et al. Body mass index before and after breast cancer diagnosis: associations with all-cause, breast cancer, and cardiovascular disease mortality. Cancer Epidemiology, Biomarkers & Prevention. 2009 May;18(5):1403-9.
• Weak effects on a marker of proliferation (Ki-67) after tumor biopsy among nondiabetic women treated with 850 mg metformin twice per day compared to placebo, with different outcomes among women with higher body mass index or waist/hip girth-ratio compared to lower measures in a mid-sized RCT⁸Bonanni B, Puntoni M et al. Dual effect of metformin on breast cancer proliferation in a randomized presurgical trial. J Clin Oncol. 2012 Jul 20;30(21):2593-600.

Our commentary: If you find these results confusing, you’re not alone. Researchers are still trying to figure out the “obesity paradox” among breast cancer survivors. What the evidence shows us so far is this:

1. People with postmenopausal breast cancer who are obese have a worse prognosis.
2. Substantial weight gain after diagnosis is linked with a worse prognosis.
3. Excessive weight loss—more than 10% of your body weight—after diagnosis is linked to higher overall mortality, but mostly from other conditions and not from breast cancer. You will need to evaluate with your doctor your own risks of breast cancer recurrence or relapse, cardiovascular disease, diabetes, and other conditions, based on your body weight, personal health history, family history, metabolic status, and other factors for each disease. Discuss what your biggest risks are and how to manage them. 
4. Modest weight loss—up to 10% of your body weight—is not a concern and could be very beneficial in reducing metabolic and other factors contributing to worse outcomes (see Optimizing your body terrain below.)

• Poorer prognosis among people with colorectal cancer who are obese in a large meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 16 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies⁹Lee J, Meyerhardt JA, Giovannucci E, Jeon JY. Association between body mass index and prognosis of colorectal cancer: a meta-analysis of prospective cohort studies. PLoS One. 2015 Mar 26;10(3):e0120706.
• No link between short-term survival and body weight among people undergoing chemotherapy for colon cancer; neither body weight nor weight gain during treatment was linked to any change in survival over the next three years or so in a large observational study¹⁰Lee DW, Cho S, Shin A, Han SW, Kim TY. Body mass index and body weight change during adjuvant chemotherapy in colon cancer patients: results from the AVANT trial. Scientific Reports. 2020 Nov 10;10(1):19467.
• 45% higher mortality among people with stage 4 colorectal cancer who were obese in the decade before their initial diagnosis compared to normal prediagnosis body mass index in a mid-sized observational study¹¹Davis JS, Chavez JC et al. Association of prediagnosis obesity and postdiagnosis aspirin with survival from stage IV colorectal cancer. JAMA Network Open. 2022 Oct 3;5(10):e2236357.

• Substantially better survival among people with metastatic melanoma who are obese and receiving targeted therapy or immunotherapy, but not chemotherapy, compared to people of normal weight in a large observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study¹²McQuade JL, Daniel CR et al. Association of body-mass index and outcomes in patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy: a retrospective, multicohort analysis. Lancet Oncology. 2018;19(3):310-322.
• Better overall survival with increasing body weight among people with advanced non-small cell lung cancer treated with immunotherapy (atezolizumab), but not those treated with chemotherapy (docetaxel) in a large observational study¹³Kichenadasse G, Miners JO et al. Association between body mass index and overall survival with immune checkpoint inhibitor therapy for advanced non-small cell lung cancer. JAMA Oncology. 2020 Apr 1;6(4):512-518.
• Better response to treatment, progression-free survival, and overall survival among overweight or obese people with advanced non-small cell lung cancer, melanoma, renal cell carcinoma, and other types of advanced cancer treated with anti-PD-1/PD-L1 inhibitors in a mid-sized observational study¹⁴Cortellini A, Bersanelli M et al. A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: when overweight becomes favorable. Journal of ImmunoTherapy of Cancer. 2019;7(1):57.

Is this survival advantage, called the obesity paradox, due to immunotherapy’s action against targets more common in cancers linked to obesity? Researchers are trying to answer this and other questions:

• Is the survival advantage more related to having been obese for a long time or for a short term?
• Did obesity contribute to the development of a subtype of cancer with the targets that immunotherapy works against?
• Is obesity driving the advantage in survival, or do obese patients tend to have a cancer that happens to have a target against which the immunotherapy is effective?

Preliminary (conflicting) evidence of better survival among people with glioblastoma multiforme who were overweight or obese; opposite impacts of body weight are seen with high-grade glioma as noted above

• No evidence of a link between risk of glioblastoma multiforme or survival after diagnosis in a large observational study¹⁵Barami K, Lyon L, Conell C. Type 2 diabetes mellitus and glioblastoma multiforme—assessing risk and survival: results of a large retrospective study and systematic review of the literature. World Neurosurgery. 2017 Oct;106:300-307.
• Better survival among people with glioblastoma multiforme who were overweight or obese compared to normal weight in a mid-sized observational study¹⁶Potharaju M, Mangaleswaran B et al. Body mass index as a prognostic marker in glioblastoma multiforme: a clinical outcome. International Journal of Radiation Oncology, Biology, Physics. 2018 Sep 1;102(1):204-209.

Until we know some of these answers, we cannot encourage you to gain weight to improve your survival. Also note that improved survival with more body weight has been found mainly among people with advanced cancer.

The connections among obesity, uncontrolled blood sugar, and insulin resistance are widely accepted in conventional medicine. Obesity is “the major risk factor of type 2 diabetes,” and after a diabetes diagnosis, “mortality rates were superior for patients with normal weight.”¹⁷Chobot A, Górowska-Kowolik K, Sokołowska M, Jarosz-Chobot P. Obesity and diabetes—not only a simple link between two epidemics. Diabetes/Metabolism Research and Reviews. 2018 Oct;34(7):e3042.

Modest evidence of better blood sugar and insulin sensitivity among people losing weight

Preliminary evidence of more weight loss among obese people who reduced high blood sugar levels

• Lower markers of insulin resistance, with a weak trendan apparent change due to a therapy, close to but not achieving full statistical significance (this is the CancerChoices definition; other researchers and studies may define this differently toward lower fasting glucose, among children who were obese who lost weight in a large meta-regression of intervention studies¹⁸Matson RI, Perry R et al. Change in obesity-related metabolic abnormalities associated with body mass index improvement through life-style intervention: a meta-regression. Pediatric Diabetes. 2020 Mar;21(2):173-193.
• Higher risk of developing insulin resistance and type 2 diabetes among people who are obese compared to people of normal weight in reviews of studies¹⁹Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006 Dec 14;444(7121):840-6; Kahn BB, Flier JS. Obesity and insulin resistance. Journal of Clinical Investigation. 2000 Aug;106(4):473-81.
• Lower levels of adiponectin, a protein linked to better insulin sensitivity, among people who are obese compared to people of normal weight in a review of studies²⁰Lihn AS, Pedersen SB, Richelsen B. Adiponectin: action, regulation and association to insulin sensitivity. Obesity Reviews. 2005 Feb;6(1):13-21.
• Better insulin sensitivity and lower HOMA-IR levels among young adult women who were overweight or obese and reduced their body weight compared to matched controls, women who relapsed to overweight or obesity, or their matched controls in a small observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study²¹Clamp LD, Hume DJ, Lambert EV, Kroff J. Enhanced insulin sensitivity in successful, long-term weight loss maintainers compared with matched controls with no weight loss history. Nutrition & Diabetes. 2017 Jun 19;7(6):e282.
• More weight loss among obese people participating in a weight-loss program of diet, education, and moderate exercise who reduced high blood sugar (hyperglycemia) compared to people with persistent high blood sugar in a small observational study²²Zalejska-Fiolka J, Birková A et al. Successful correction of hyperglycemia is critical for weight loss and a decrease in cardiovascular risk in obese patients. Journal of Nutritional Biochemistry. 2022 Aug;106:109021.

The connection between obesity and hormone imbalance is widely accepted in conventional medicine. “Fat cells have a tendency to produce high levels of estrogen that may increase the risk of breast and gynecologic cancers.”²³Obesity and cancer: Increasing risks, complicating treatments. Cancer Treatment Centers of America. February 8, 2021. Viewed September 21, 2021.

Obesity-related immune cell infiltration, along with inflammation and increased oxidative stress, promote metabolic impairments in insulin-sensitive tissues, leading eventually to insulin resistance, organ failure, and premature aging.²⁴Daryabor G, Atashzar MR, Kabelitz D, Meri S, Kalantar K. The effects of type 2 diabetes mellitus on organ metabolism and the immune system. Frontiers in Immunology. 2020 Jul 22;11:1582.

During obesity, the insulin signaling pathway is deregulated, establishing a state of low-grade systemic inflammation.²⁵Ieronymaki E, Daskalaki MG, Lyroni K, Tsatsanis C. Insulin signaling and insulin resistance facilitate trained immunity in macrophages through metabolic and epigenetic changes. Frontiers in Immunology. 2019 Jun 12;10:1330. As the main inducer of systemic low-level inflammation, obesity is a main risk factor for type 2 diabetes. Obesity-related inflammation, along with immune cell infiltration and increased oxidative stress, promote metabolic impairments in insulin-sensitive tissues, leading eventually to insulin resistance, organ failure, and premature aging.²⁶Daryabor G, Atashzar MR, Kabelitz D, Meri S, Kalantar K. The effects of type 2 diabetes mellitus on organ metabolism and the immune system. Frontiers in Immunology. 2020 Jul 22;11:1582.

Good evidence of a link between obesity and inflammation

Modest evidence of less inflammation among people losing excess weight

• Low-grade chronic inflammatory state among people who are obese compared to people of normal weight in a review of 19 studies rated as excellent quality²⁷Battineni G, Sagaro GG et al. Impact of obesity-induced inflammation on cardiovascular diseases (CVD). International Journal of Molecular Sciences. 2021 Apr 30;22(9):4798.
• Lower marker of inflammation (C-reactive protein) among children who were obese with weight loss compared to baseline in a meta-regression of 68 intervention studies²⁸Matson RI, Perry R et al. Change in obesity-related metabolic abnormalities associated with body mass index improvement through life-style intervention: a meta-regression. Pediatric Diabetes. 2020 Mar;21(2):173-193.

Obesity induces oxidative stress.²⁹Ieronymaki E, Daskalaki MG, Lyroni K, Tsatsanis C. Insulin signaling and insulin resistance facilitate trained immunity in macrophages through metabolic and epigenetic changes. Frontiers in Immunology. 2019 Jun 12;10:1330. This increased oxidative stress, along with immune cell infiltration and inflammation, promote metabolic impairments in insulin-sensitive tissues, leading eventually to insulin resistance, organ failure, and premature aging.³⁰Daryabor G, Atashzar MR, Kabelitz D, Meri S, Kalantar K. The effects of type 2 diabetes mellitus on organ metabolism and the immune system. Frontiers in Immunology. 2020 Jul 22;11:1582.

Obesity is linked to lower microbial diversity.³¹Gérard C, Vidal H. Impact of Gut Microbiota on Host Glycemic Control. Frontiers in Endocrinology (Lausanne). 2019 Jan 30;10:29.

• A change in the ratio of some microbes, with fewer beneficial microbes and more harmful ones, with weight gain beyond a normal body weight, and then a reversal in the ratio with weight loss, in a review of studies³²Mathur R, Barlow GM. Obesity and the microbiome. Expert Review of Gastroenterology & Hepatology. 2015 Jun;9(8):1087-1099.
• Changes in the composition of the intestinal microbiota linked to obesity in a review³³Hartstra AV, Bouter KE, Bäckhed F, Nieuwdorp M. Insights into the role of the microbiome in obesity and type 2 diabetes. Diabetes Care. 2015 Jan;38(1):159-65.
• Partial reversal of obesity-associated microbial and metabolic changes with weight loss among both humans and mice who are obese in a review of studies³⁴Liu R, Hong et al. Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention. Nature Medicine. 2017 Jul;23(7):859-868.

• Higher risk of low vitamin D levels among people with high body mass index compared to other people in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 4 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies³⁵Xu J, Yuan X et al. Association of circulating 25-hydroxyvitamin D levels with colorectal cancer: an updated meta-analysis. Journal of Nutritional Science and Vitaminology (Tokyo). 2018;64(6):432-444.

Longer chromosomal telomeres are strongly linked to longer survival.³⁶von Zglinicki T, Saretzki G, Passos J. Aging and telomeres. Reference Module in Biomedical Sciences. Elsevier. 2014.

Good evidence of a link between telomere length and body mass index

• Shorter telomere length, especially in younger individuals, among people with higher body mass index (BMI) in a very large meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 87 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies³⁷Gielen M, Hageman GJ et al; TELOMAAS group. Body mass index is negatively associated with telomere length: a collaborative cross-sectional meta-analysis of 87 observational studies. American Journal of Clinical Nutrition. 2018 Sep 1;108(3):453-475.

• Bigger improvements in scores in five cognitive domains among postmenopausal women with breast cancer and not taking metformin with the highest baseline BMIs participating in a weight-loss intervention compared to no intervention and compared to lower baseline BMIs in a mid-sized RCTrandomized controlled trial, a study design in which people are randomly assigned to either an experimental group or a control group to compare the outcomes from different treatments; an RCT is considered a strong design for determining a therapy’s effects³⁸Hartman SJ, Nelson SH et al. The effects of weight loss and metformin on cognition among breast cancer survivors: evidence from the Reach for Health study. Psycho-Oncology. 2019 Aug;28(8):1640-1646.

• A link between a large waist-to-hip ratio and depression among middle-aged women in a mid-sized observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study³⁹Wing RR, Matthews KA, Kuller LH, Meilahn EN, Plantinga P. Waist to hip ratio in middle-aged women. Associations with behavioral and psychosocial factors and with changes in cardiovascular risk factors. Arteriosclerosis and Thrombosis. 1991 Sep-Oct;11(5):1250-7.

• Higher risk of treatment-related lymphedema among people with breast cancer who are obese compared to normal-weight survivors in a review of 60 clinical studies⁴⁰Paskett ED, Dean JA, Oliveri JM, Harrop JP. Cancer-related lymphedema risk factors, diagnosis, treatment, and impact: a review. Journal of Clinical Oncology. 2012 Oct 20;30(30):3726-33.

Surgery outcomes:

Good evidence of longer surgery times, higher illness (morbidity) after surgery, and higher rates of conversion from laparoscopic to open surgery among people who are obese

• Longer surgery time, more blood loss, and higher incidence of intra-abdominal infection during stomach cancer surgery among people who are obese compared to other people in a mid-sized observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study⁴¹Kodera Y, Ito S et al. Obesity and outcome of distal gastrectomy with D2 lymphadenectomy for carcinoma. Hepatogastroenterology. 2004 Jul-Aug;51(58):1225-8.
• Higher conversion from laparoscopic to open surgery, longer laparoscopic colorectal surgery time, and higher morbiditya state of being unhealthy due a particular disease or situation after surgery among people who are obese compared to others in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 8 observational studies⁴²Zhou Y, Wu L, Li X, Wu X, Li B. Outcome of laparoscopic colorectal surgery in obese and nonobese patients: a meta-analysis. Surgical Endoscopy. 2012 Mar;26(3):783-9.
• Substantially longer surgery time and higher rates of conversion from laparoscopic colorectal surgery to open surgery, higher morbidity, more surgical site infection, and more anastomotic leakage among people with more visceral fat compared to other people in a meta-analysis of 4 observational studies⁴³Yang T, Wei M, He Y, Deng X, Wang Z. Impact of visceral obesity on outcomes of laparoscopic colorectal surgery: a meta-analysis. ANZ Journal of Surgery. 2015 Jul-Aug;85(7-8):507-13.
• Longer surgery time and greater blood loss during radical prostatectomy among people with obesity (BMI of 30 or higher) compared to other people in a mid-sized observational study⁴⁴Lindner U, Lawrentschuk N, Abouassaly R, Fleshner NE, Trachtenberg J. Radical prostatectomy in obese patients: improved surgical outcomes in recent years. International Journal of Urology. 2010 Aug;17(8):727-32.

Good evidence of higher risk of infection and other complications related to surgery among people who are obese

Modest evidence of higher risk of surgical site infection among people who are obese

• Higher risks of wound infection after esophageal surgery among people with excess body weight compared to people of normal weight in a large meta-analysis of 19 studies⁴⁵Gao H, Feng HM et al. Impact of high body mass index on surgical outcomes and long-term survival among patients undergoing esophagectomy: a meta-analysis. Medicine (Baltimore). 2018 Jul;97(28):e11091.
• Three times the risk of complications and blood transfusions during surgery, plus greater risk of incontinence after surgery, among men treated with radical prostatectomy for prostate cancer with obesity compared to normal body weight in a mid-sized observational study⁴⁶Gucci M, Sebastianelli A et al. Role of abdominal obesity for functional outcomes and complications in men treated with radical prostatectomy for prostate cancer: results of the Multicenter Italian Report on Radical Prostatectomy (MIRROR) study. Scandinavian Journal of Urology. 2014 Apr;48(2):138-45.
• Higher risk of sternal wound infection during bilateral internal mammary artery grafting among people who are obese compared to other people in a mid-sized observational study⁴⁷He GW, Ryan WH, Acuff TE, Bowman RT, Douthit MB, Yang CQ, Mack MJ. Risk factors for operative mortality and sternal wound infection in bilateral internal mammary artery grafting. Journal of Thoracic and Cardiovascular Surgery. 1994 Jan;107(1):196-202.
• Higher risk of surgical site infection among people who are obese in a large observational study⁴⁸Barber GR, Miransky J et al. Direct observations of surgical wound infections at a comprehensive cancer center. Archives of Surgery 1995;130(10):1042-7.

Good evidence of higher risks of cardiovascular complications after surgery among people with excess body weight

• Higher risks of cardiovascular complications after esophageal surgery among people with excess body weight compared to people of normal weight in a large meta-analysis of 19 studies⁴⁹Gao H, Feng HM et al. Impact of high body mass index on surgical outcomes and long-term survival among patients undergoing esophagectomy: a meta-analysis. Medicine (Baltimore). 2018 Jul;97(28):e11091.

Good evidence of substantially higher risk of blood clots after surgery among women with body mass index (BMI) of 25 or higher

• Substantially higher risk of blood clots after surgery among women with body mass index (BMI) of 25 or higher, and increasing risk as BMI increased, compared to BMI less than 25 in a very large observational study⁵⁰Parkin L, Sweetland S et al. Million Women Study Collaborators. Body mass index, surgery, and risk of venous thromboembolism in middle-aged women: a cohort study. Circulation 2012;125:1897–904.

Anxiety: good evidence of a link between obesity and anxiety (not specific to cancer)

• A link between greater anxiety and obesity in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 16 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies not specific to cancer⁵¹Gariepy G, Nitka D, Schmitz N. The association between obesity and anxiety disorders in the population: a systematic review and meta-analysis. International Journal of Obesity (London). 2010 Mar;34(3):407-19.
• Increased frequency of anxiety among people with increasing body weight in meta-analysis of 25 observational studies not specific to cancer⁵²Amiri S, Behnezhad S. Obesity and anxiety symptoms: a systematic review and meta-analysis. Neuropsychiatrie. 2019 Jun;33(2):72-89. English.

Depression: preliminary evidencesignificant effects in small or poorly designed clinical studies OR conflicting results in adequate studies but a preponderance of evidence of an effect (this is the CancerChoices definition; other researchers and studies may define this differently) of a link between a large waist-to-hip ratio and depression among middle-aged women (not specific to cancer)

• Higher incidence of a large waist-to-hip ratio among middle-aged women with higher levels of depression compared to others in a mid-sized observational study⁵³Wing RR, Matthews KA, Kuller LH, Meilahn EN, Plantinga P. Waist to hip ratio in middle-aged women. Associations with behavioral and psychosocial factors and with changes in cardiovascular risk factors. Arteriosclerosis and Thrombosis. 1991 Sep-Oct;11(5):1250-7.

Pain: modest evidence of higher risk of pain (not specific to cancer) among people with obesity and less pain among those losing weight

Obesity is a risk factor for chronic pain.⁵⁴Totsch SK, Waite ME, Sorge RE. Dietary influence on pain via the immune system. Progress in Molecular Biology and Translational Science. 2015;131:435-69.

• Higher risk of pain among people who experience overweight/obesity early in life compared to other people, and treatments for obesity reduce pain secondary to weight loss in a review of observational studies⁵⁵Janke EA, Collins A, Kozak AT. Overview of the relationship between pain and obesity: What do we know? Where do we go next? Journal of Rehabilitation Research & Development. 2007;44(2):245-62.
• More weight loss and less pain among people with knee osteoarthritis participating in an intensive low-energy diet maintained by frequent consultations with a dietician compared to minimal attention in a small RCT⁵⁶Bliddal H, Leeds AR, Stigsgaard L, Astrup A, Christensen R. Weight loss as treatment for knee osteoarthritis symptoms in obese patients: 1-year results from a randomised controlled trial. Annals of the Rheumatic Diseases. 2011 Oct;70(10):1798-803.
• Higher risk of chronic pain among elderly obese people (BMI 30–34.9) and four times the risk among severely obese people (BMI≥35) compared to elderly people of normal weight (BMI 18.5–24.9) in a mid-sized observational study⁵⁷McCarthy LH, Bigal ME, Katz M, Derby C, Lipton RB. Chronic pain and obesity in the elderly: results from the Einstein aging study. Journal of the American Geriatrics Society. 2009 Jan;57(1):115-9.
• Substantially higher risk of pain among people with central obesity compared to other people in a mid-sized observational study⁵⁸Ray L, Lipton RB, Zimmerman ME, Katz MJ, Derby CA. Mechanisms of association between obesity and chronic pain in the elderly. Pain. 2011 Jan;152(1):53-59.

Stress: no evidence of an effectoverall, one or more studies did not demonstrate that a treatment or intervention led to an expected outcome; this does not always mean that there is no effect in clinical practice, but that the studies may have been underpowered (too few participants) or poorly designed. Larger, well-designed studies provide more confidence in making assessments. of moderate weight loss (about 8 pounds) on self-reported stress among adults with excess weight or obesity in a combined analysis of studies (not specific to cancer)

• No effect on self-reported stress with diet-induced weight loss averaging about 8 pounds among adults with excess weight or obesity compared to those who did not lose weight in a meta-analysis of 10 RCTs⁵⁹Booth AO, Wang X, Turner AI, Nowson CA, Torres SJ. Diet-induced weight loss has no effect on psychological stress in overweight and obese adults: a meta-analysis of randomized controlled trials. Nutrients. 2018 May 14;10(5):613.

• 17% higher risk of breast cancer diagnosis after menopause with each 5 BMI units, such as a BMI change from 25 to 30 of adult weight gain in a very large meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 126 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies⁶¹Chan DSM, Abar L et al. World Cancer Research Fund International: Continuous Update Project-systematic literature review and meta-analysis of observational cohort studies on physical activity, sedentary behavior, adiposity, and weight change and breast cancer risk. Cancer Causes & Control. 2019 Nov;30(11):1183-1200.
• 14% higher risk of a breast cancer diagnosis among postmenopausal white women genetically predisposed to breast cancer with body mass index (BMI) of 25 or higher in a large observational study⁶²Al Ajmi K, Lophatananon A, Mekli K, Ollier W, Muir KR. Association of nongenetic factors with breast cancer risk in genetically predisposed groups of women in the UK Biobank Cohort. JAMA Network Open. 2020;3(4):e203760.
• Higher risk of breast cancer with larger waist circumferences (14 studies) or waist-to-hip ratio (15 studies) among postmenopausal women, but not premenopausal women, in a meta-analysis of observational studies⁶³Chen GC, Chen SJ et al. Central obesity and risks of pre- and postmenopausal breast cancer: a dose-response meta-analysis of prospective studies. Obesity Reviews. 2016 Nov;17(11):1167-1177.
• A moderately higher risk of breast cancer with larger waist-to-hip ratio among women, with a slightly higher risk with premenopausal women compared to postmenopausal women in a meta-analysis of observational studies⁶⁴Connolly BS, Barnett C, Vogt KN, Li T, Stone J, Boyd NF. A meta-analysis of published literature on waist-to-hip ratio and risk of breast cancer. Nutrition and Cancer. 2002;44(2):127-38.
• Lower risk of breast cancer with weight loss in a very large meta-analysis of 139 observational studies⁶⁵Hardefeldt PJ, Penninkilampi R, Edirimanne S, Eslick GD. Physical activity and weight loss reduce the risk of breast cancer: a meta-analysis of 139 prospective and retrospective studies. Clinical Breast Cancer. 2018 Aug;18(4):e601-e612. Our note: We assume weight loss is beneficial if you’re overweight at baseline.
• 10–15% lower risk of breast cancer—both before and after menopause—with adult weight loss in a very large meta-analysis of 126 observational studies⁶⁶Chan DSM, Abar L et al. World Cancer Research Fund International: Continuous Update Project-systematic literature review and meta-analysis of observational cohort studies on physical activity, sedentary behavior, adiposity, and weight change and breast cancer risk. Cancer Causes & Control. 2019 Nov;30(11):1183-1200.
• Higher risk of second primary cancers among people with breast cancer with higher BMI in a large observational study⁶⁷Feigelson HS, Bodelon C, Powers JD et al. Body mass index and risk of second cancer among women with breast cancer. Journal of the National Cancer Institute. 2021 Apr 5:djab053.
• 14% lower risk of premenopausal breast cancer with each increase of 5 BMI units, such as a BMI change from 25 to 30, among women aged 18–30, but adult weight gain and greater overweight or obesity increased breast cancer risk in postmenopausal women, but only for HR+ but not HR- breast cancers ia very large meta-analysis of 126 observational studies⁶⁸Chan DSM, Abar L et al. World Cancer Research Fund International: Continuous Update Project-systematic literature review and meta-analysis of observational cohort studies on physical activity, sedentary behavior, adiposity, and weight change and breast cancer risk. Cancer Causes & Control. 2019 Nov;30(11):1183-1200.
• 18% lower risk of breast cancer among women 50 years and older not using postmenopausal hormones with weight loss of more than 4.4 pounds (2 kilograms), increasing to 32% lower risk among women losing 20 pounds (9 kilograms), sustained over approximately 10 years or more in a large observational study⁶⁹Teras LR, Patel AV et al. Sustained weight loss and risk of breast cancer in women ≥50 years: a pooled analysis of prospective data. Journal of the National Cancer Institute. 2019;djz226.

• 18% higher risk of colon cancer among young adults who are overweight or obese compared with those with normal weight, but less association among women and rectal cancer, in a very large meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 15 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies⁷⁰Lei X, Song S, Li X, Geng C, Wang C. Excessive body fat at a young age increases the risk of colorectal cancer: a systematic review and meta-analysis. Nutrition and Cancer. 2021;73(9):1601-1612.
• 23-59% higher risk of colorectal cancer (depending on the specific site) with higher body mass index (BMI) in a meta-analysis of 30 observational studies⁷¹Robsahm TE, Aagnes B et al. Body mass index, physical activity, and colorectal cancer by anatomical subsites: a systematic review and meta-analysis of cohort studies. European Journal of Cancer Prevention. 2013 Nov;22(6):492-505.
• 20% higher risk of colorectal cancer among people with obesity compared with people without obesity in a meta-analysis of 103 observational studies⁷²Huxley RR, Ansary-Moghaddam A, Clifton P, Czernichow S, Parr CL, Woodward M. The impact of dietary and lifestyle risk factors on risk of colorectal cancer: a quantitative overview of the epidemiological evidence. International Journal of Cancer. 2009 Jul 1;125(1):171-80.
• 40% higher risk of colorectal serrated polyps with high body mass index (BMI) in a meta-analysis of observational or interventional studies⁷³Bailie L, Loughrey MB, Coleman HG. Lifestyle risk factors for serrated colorectal polyps: a systematic review and meta-analysis. Gastroenterology. 2017 Jan;152(1):92-104.
• Higher risk of colorectal cancer-specific mortality among people who are obese before diagnosis compared to people of normal weight in a large meta-analysis of 16 observational studies⁷⁴Lee J, Meyerhardt JA, Giovannucci E, Jeon JY. Association between body mass index and prognosis of colorectal cancer: a meta-analysis of prospective cohort studies. PLoS One. 2015 Mar 26;10(3):e0120706.

Esophageal cancer: good evidence of higher risk of esophageal squamous cell carcinomas but not adenocarcinomas among people with higher body mass index

• Higher risk of esophageal squamous cell carcinomas, but lower risk of esophageal adenocarcinomas with higher body mass index (BMI) in a review of 100 meta-analysesa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies⁷⁵Castro C, Peleteiro B, Lunet N. Modifiable factors and esophageal cancer: a systematic review of published meta-analyses. Journal of Gastroenterology. 2018 Jan;53(1):37-51.

Gallbladder cancer: good evidence of moderately higher risk of gallbladder cancer among people with excess body weight

• 24% higher risk of gallbladder cancer with higher body weight in a very large meta-analysis of 19 observational studies⁷⁶Campbell PT, Newton CC et al. Body size indicators and risk of gallbladder cancer: pooled analysis of individual-level data from 19 prospective cohort studies. Cancer Epidemiology, Biomarkers & Prevention. 2017 Apr;26(4):597-606.

• 6% increased risk of ovarian cancer with each 5 BMI units, such as a BMI change from 25 to 30, of excess weight in a large meta-analysesa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 25 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies⁷⁷Continuous Update Project. Diet, Nutrition, Physical Activity and Ovarian Cancer. World Cancer Research Fund International. Revised 2018. Viewed September 22, 2021.

• Moderately higher risk of pancreatic cancer mortality among people without cancer at baseline with higher body mass index (BMI) during early adulthood, and slightly higher risk with higher waist-to-hip ratio or waist circumference in a very large pooled analysis of 20 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies⁷⁸Genkinger JM, Kitahara CM et al. Central adiposity, obesity during early adulthood, and pancreatic cancer mortality in a pooled analysis of cohort studies. Annals of Oncology. 2015 Nov;26(11):2257-66.

• 94% higher risk of recurrence risk after prostatectomy with weight gain after a prostate cancer diagnosis in a large observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods study⁷⁹Joshu CE, Mondul AM et al. Weight gain is associated with an increased risk of prostate cancer recurrence after prostatectomy in the PSA era. Cancer Prevention Research (Philadelphia, Pa.). 2011 Apr;4(4):544-51.

• 35% higher risk of thyroid cancer among people with high body mass index (BMI) in a meta-analysisa statistical analysis that combines the results of two or more research studies; the results of smaller research studies addressing the same or similar questions can be analyzed as though they are one bigger, more powerful study of 42 observationala type of study in which individuals are observed or certain outcomes are measured, but no attempt is made to affect the outcome (for example, no treatment is given); an example is a study that records people’s diets, but doesn’t try to alter their diets, and looks for patterns of disease or other outcomes related to different foods studies⁸⁰Yin DT, He H et al. The association between thyroid cancer and insulin resistance, metabolic syndrome and its components: a systematic review and meta-analysis. International Journal of Surgery. 2018 Sep;57:66-75.