A growing concern; Obesity, metabolic syndrome and cancer risk

By: Saritha Uppala, M.D. Internal Medicine Grandview Medical Group


Common chronic diseases include Diabetes, stroke, cancer, heart disease & Osteoporosis. Cancer and cardiovascular disease is the major cause for morbidity and mortality worldwide, with cancer expected to results in 571,950 deaths per year in US. Most common leading cause of cancer continues to be related to tobacco use. Evidence shows that obese men and women are at greater risk of developing cancer and worsening of chronic conditions than non-obese.

Obesity is defined as body mass index (BMI > 30Kg/m2) or greater. In the past 30 years, its prevalence increased worldwide, more than 35% of adults and 20% of children are currently obese in United States. Majority of these obese individuals meet the criteria for metabolic dysfunction characterized by increased waist circumference, insulin resistance, hyperglycemia, hypertension and hypertriglyceridemia.

Which cancers link to obesity, diet or physical activity?

In 2007 AICR (American Institute of Cancer Research) expert report examined the evidence linking various lifestyle factors including diet, physical activity and body weight to cancer at 17 body sites using systematic literature review. There is strong evidence lifestyle linked to more than 12 cancers in men and women, including colon, rectal, pancreatic, gallbladder, renal, malignant melanoma, breast, endometrial cancer, non-Hodgkin’s lymphoma, esophageal, leukemia, multiple myeloma, thyroid cancer, liver prostrate etc. Another comprehensive report complimented to these findings is meta-analysis ( Dobbins et al )of 98 studies done 18 countries from 1985 to 2011 -revealed 8 tumor sites in men and 5 in women has strong association between obesity and cancer . Another 16 year prospective study done in 900, 000 US population done from 1982 till 1998, revealed risk of mortality from these cancers high in men and women with BMI higher than 35. In individuals with colon cancer , BMI greater than 40 has higher risk of mortality than others

 Higher the BMI, higher the risk of colon and rectal cancer in men and colon cancer in women. It was shown a risk association of 9% increase in colon cancer for every 5 Units of BMI increase as compared to individuals with normal BMI , similar impact was seen in pancreatic cancer and increased abdominal fat and waist circumference .


Are there possible mechanisms linking obesity and cancer?

Excess body weight can elevate insulin levels, high triglycerides leading increased levels of metabolic hormones like IGF -1 , leptin and adiponectin. Especially in insulin resistance , disrupted glucose metabolism leading to enhancements in chronic, low grade inflammatory state may contribute to growth signaling , vascular signal , cell enrichment for cancer susceptibility , tumor initiation and invasion and metastasis , poor prognosis. These inflammatory markers include interleukin-1beta, IL -6, TNF –alfa, MCP -1. PAI -1 , a serine protease inhibitor is also produced by visceral adipose tissue , increase levels commonly found in obese people associated with risk of atherogenesis, CVD risk and caner.

The magnitude of the association between cancer and obesity risk is noteworthy and could be avoided with reduction in obesity.


Does weight loss improve outcomes?

Weight loss itself has been shown to decrease cancer risk and when we add other life style modifications including exercise has beneficial affect -by altering metabolism thereby slowed tumor growth.

In 2001 International Agency for Cancer Research Committee reports looked at levels of evidence and physical activity and their data supports physically active life style lowers colon cancer risk and also substantial evidence in decrease in breast cancer up to 20 -40% in most active women compared to sedentary women.

Up to 12% decrease in colorectal cancer in individuals who did 30 minutes of recreational physical activity which is equivalent to brisk walking. Increase in physical activity reduces insulin resistance , chronic inflammatory state and also releases circulatory myokines which are anticancer (SPARC and calprotectin)

 Patient who achieved weight loss demonstrated significant improvement in a variety of metabolic conditions such as hypertriglyceridemia, Diabetes, HDL 40% decrease in longterm mortality from any cause.