What is known about the relationship between obesity and cancer?

Obesity is associated with increased risks of the following cancer types, and possibly others as well:

• Esophagus
• Pancreas
• Colon and rectum
• Breast (after menopause)
• Endometrium (lining of the uterus)
• Kidney
• Thyroid
• Gallbladder

One study, using NCI Surveillance, Epidemiology, and End Results (SEER) data, estimated that in 2007 in the United States, about 34,000 new cases of cancer in men (4 percent) and 50,500 in women (7 percent) were due to obesity. The percentage of cases attributed to obesity varied widely for different cancer types but was as high as 40 percent for some cancers, particularly endometrial cancer and esophageal adenocarcinoma.

A projection of the future health and economic burden of obesity in 2030 estimated that continuation of existing trends in obesity will lead to about 500,000 additional cases of cancer in the United States by 2030. This analysis also found that if every adult reduced their BMI by 1 percent, which would be equivalent to a weight loss of roughly 1 kg (or 2.2 lbs) for an adult of average weight, this would prevent the increase in the number of cancer cases and actually result in the avoidance of about 100,000 new cases of cancer.

Several possible mechanisms have been suggested to explain the association of obesity with increased risk of certain cancers:

• Fat tissue produces excess amounts of estrogen, high levels of which have been associated with the risk of breast, endometrial, and some other cancers.
• Obese people often have increased levels of insulin and insulin-like growth factor-1 (IGF-1) in their blood (a condition known as hyperinsulinemia or insulin resistance), which may promote the development of certain tumors.
• Fat cells produce hormones, called adipokines, that may stimulate or inhibit cell growth. For example, leptin, which is more abundant in obese people, seems to promote cell proliferation, whereas adiponectin, which is less abundant in obese people, may have antiproliferative effects.
• Fat cells may also have direct and indirect effects on other tumor growth regulators, including mammalian target of rapamycin (mTOR) and AMP-activated protein kinase.
• Obese people often have chronic low-level, or “subacute,” inflammation, which has been associated with increased cancer risk.

Other possible mechanisms include altered immune responses, effects on the nuclear factor kappa beta system, and oxidative stress.

Many studies have shown that overweight and obesity are associated with a modest increase in risk of postmenopausal breast cancer. This higher risk is seen mainly in women who have never used menopausal hormone therapy (MHT) and for tumors that express both estrogen and progesterone receptors.

Overweight and obesity have, by contrast, been found to be associated with a reduced risk of premenopausal breast cancer in some studies.

The relationship between obesity and breast cancer may be affected by the stage of life in which a woman gains weight and becomes obese. Epidemiologists are actively working to address this question. Weight gain during adult life, most often from about age 18 to between the ages of 50 and 60, has been consistently associated with risk of breast cancer after menopause.

The increased risk of postmenopausal breast cancer is thought to be due to increased levels of estrogen in obese women. After menopause, when the ovaries stop producing hormones, fat tissue becomes the most important source of estrogen. Because obese women have more fat tissue, their estrogen levels are higher, potentially leading to more rapid growth of estrogen-responsive breast tumors.

The relationship between obesity and breast cancer risk may also vary by race and ethnicity. There is limited evidence that the risk associated with overweight and obesity may be less among African American and Hispanic women than among white women.

Overweight and obesity have been consistently associated with endometrial cancer, which is cancer of the lining of the uterus. Obese and overweight women have two to four times the risk of developing this disease than women of a normal weight, regardless of menopausal status. Many studies have also found that the risk of endometrial cancer increases with increasing weight gain in adulthood, particularly among women who have never used MHT.

Although it has not yet been determined why obesity is a risk factor for endometrial cancer, some evidence points to a role for diabetes, possibly in combination with low levels of physical activity. High levels of estrogen produced by fat tissue are also likely to play a role.

Among men, a higher BMI is strongly associated with increased risk of colorectal cancer. The distribution of body fat appears to be an important factor, with abdominal obesity, which can be measured by waist circumference, showing the strongest association with colon cancer risk.

An association between BMI and waist circumference with colon cancer risk is also seen in women, but it is weaker. Use of MHT may modify the association in postmenopausal women.

A number of mechanisms have been proposed to account for the association of obesity with increased colon cancer risk. One hypothesis is that high levels of insulin or insulin-related growth factors in obese people may promote colon cancer development.

High BMI is also associated with rectal cancer risk, but the increase in risk is more modest.

Obesity has been consistently associated with renal cell cancer, which is the most common form of kidney cancer, in both men and women. The mechanisms by which obesity may increase renal cell cancer risk are not well understood. High blood pressure is a known risk factor for renal cell cancer, but the relationship between obesity and kidney cancer is independent of blood pressure status. High levels of insulin may play a role in the development of the disease.

Overweight and obese people are about twice as likely as people of healthy weight to develop a type of esophageal cancer called esophageal adenocarcinoma. Most studies have observed no increased risk, or even a decline in risk, with obesity for the other major type of esophageal cancer, squamous cell cancer.

The mechanisms by which obesity may increase risk of esophageal adenocarcinoma are not well understood. However, overweight and obese people are more likely than people of normal weight to have a history of gastroesophageal reflux disease or Barrett esophagus, which are associated with an increased risk of esophageal adenocarcinoma. It is possible that obesity exacerbates the esophageal inflammation that is associated with these conditions.

Many studies have reported a slight increase in risk of pancreatic cancer among overweight and obese individuals. Waist circumference may be a particularly important factor in the association of overweight and obesity with pancreatic cancer.

Increasing weight has been found to be associated with an increase in the risk of thyroid cancer. It is unclear what the mechanism might be.

The risk of gallbladder cancer increases with increasing BMI. The increase in risk may be due to the higher frequency of gallstones, a strong risk factor for gallbladder cancer, in obese individuals.

The relationship between obesity and prostate cancer has been studied extensively. The results of individual studies do not suggest a consistent association between obesity and prostate cancer. However, when the data from multiple studies are pooled, analyses show that obesity may be associated with a very slight increase in the risk of prostate cancer.

In addition, several studies have found that obese men have a higher risk of aggressive prostate cancer than men of healthy weight. Generally, risk of prostate cancer has been linked to levels of certain hormones and growth factors, especially IGF-1.

Some studies have shown a weak association between increasing BMI and risk of ovarian cancer, especially in premenopausal women, although other studies have not found an association. As with some other cancers, an association between ovarian cancer and obesity may reflect increased levels of estrogens.

Some evidence links obesity to liver cancer and to some types of lymphoma and leukemia, but additional studies are needed to confirm these associations.