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Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms

Abstract

The prevalence of obesity is rapidly increasing globally. Epidemiological studies have associated obesity with a range of cancer types, although the mechanisms by which obesity induces or promotes tumorigenesis vary by cancer site. These include insulin resistance and resultant chronic hyperinsulinaemia, increased bioavailability of steroid hormones and localized inflammation. Gaining a better understanding of the relationship between obesity and cancer can provide new insight into mechanisms of cancer pathogenesis.

Key Points

  • The International Agency for Research on Cancer has determined that, based on results from epidemiological studies, people who are overweight or obese are at increased risk of developing several cancer types, including adenocarcinoma of the oesophagus, colon cancer, breast cancer (in postmenopausal women), endometrial cancer and kidney (renal-cell) cancer.

  • Epidemiological evidence also indicates that cancers of the liver, gallbladder and pancreas are obesity related, and that obesity might also increase risk for haematopoietic cancers and for aggressive prostate cancer. No association is seen between obesity and lung cancer. Results for other cancers have been inconsistent.

  • Insulin resistance develops as a metabolic adaptation to increased levels of circulating free fatty acids released from adipose tissue, especially intra-abdominal adipose. Insulin resistance is generally compensated by increased pancreatic insulin secretion. There is mounting epidemiological and experimental evidence to indicate that chronic hyperinsulinaemia increases risk of cancers of the colon and endometrium, and probably other tumours (for example, of the pancreas and kidney).

  • Serum levels of insulin-like growth factor 1 (IGF1) are also associated with different forms of cancer. However, there is no simple, direct relationship between circulating levels of IGF1 and the degree of adiposity.

  • Circulating levels of oestrogens are strongly related to adiposity. For cancers of the breast (in postmenopausal women) and endometrium, the effects of overweight and obesity on cancer risk are largely mediated by increased oestrogen levels.

  • In 4–8% of premenopausal women, obesity and ensuing insulin resistance can either cause or aggravate syndromes of ovarian androgen excess (polycystic ovary syndrome) and chronic progesterone deficiency. There is strong evidence that such syndromes, along with reduced progesterone production, increase the risk of endometrial cancer.

  • Successful intervention strategies for weight loss and maintenance at the individual and community level are needed to reduce cancer risk.

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The authors declare no competing financial interests.

Correspondence to Eugenia E. Calle.

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Glossary

TRIGLYCERIDE

A fat that is synthesized from carbohydrates and stored in animal adipose cells. On hydrolysis, it releases free fatty acids into the blood.

ANTHROPOMETRIC

A measurement of the size or proportions of the human body; for example, weight, height and waist circumference.

RELATIVE RISK

The risk of cancer (or other disease) in a group of exposed persons divided by the risk in a group of unexposed persons. The relative risk is a commonly used measure of association in epidemiological studies.

CENTRAL ADIPOSITY

The storage of adipose tissue preferentially in adipocytes on or within the trunk rather than the extremities.

ANOVULATORY

A menstrual cycle that is not accompanied by the discharge of an egg from the ovary.

PROXY RESPONDERS

Also called surrogate responders, individuals who provide information regarding exposure in place of the individual involved in the study.

SEX STEROIDS

A family of hormones that all share a basic chemical (steroidal) structure. These hormones include androgens, oestrogens and progesterone, and have important effects on sexual development and reproductive functions.

FASTING AND NON-FASTING GLUCOSE LEVELS

Glucose is the end product of carbohydrate metabolism and the chief source of energy for living organisms; its utilization is controlled by insulin. It is found in the blood of all animals. Fasting plasma glucose levels are a measurement of the concentration of glucose in the plasma after the patient has not eaten for at least 8 hours.

BIOAVAILABLE

The portion of a substance that can be used physiologically by target tissues.

NON-ALCOHOLIC STEATOHEPATITIS.

A liver lesion characterized by liver cell injury and death, and hepatic inflammation that can be accompanied by progressive hepatic fibrosis.

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Further reading

Figure 1: Obesity trends.
Figure 2: Effects of obesity on growth-factor production.
Figure 3: Effects of obesity on hormone production.
Figure 4: Obesity, hormones and endometrial cancer.