Why is Obesity a Modifiable Risk Factor for Cancer?

Abida Taher, MD, PhDSeptember 03, 2023

Know the link between obesity and cancer to reduce your risk of cancer.

“As we become more successful with tobacco control, we are left with obesity as a dominant cause of cancer, and the United States is leading the world in the level of overweight and obese people.”
- Graham A. Colditz, MD, DrPH, MPH, Associate Director of Prevention and Control at the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri, and Chair of the IARC working group.

Being overweight or obese describes having more body fat (adipose tissue) than what is considered healthy. More than one-third of adults in the US have obesity, which is defined as having a BMI (Body Mass Index) greater than 30.

Being overweight or having obesity is, among other things, linked with a higher risk of getting 13 types of cancer. These cancers make up nearly 40% of all cancers diagnosed in the United States each year, including but not limited to breast cancer in postmenopausal women, esophageal, colon, rectal, uterine, stomach, and gallbladder cancer.

According to research from the American Cancer Society, excess body weight is thought to be responsible for about 11% of cancers in women and about 5% of cancers in men in the United States, as well as about 7% of all cancer deaths.

“Obesity may be as important as smoking as a contributor to overall mortality and cancer, and may even surpass it. Obesity, particularly visceral fat, leads to physiological changes and a range of effects, including insulin resistance, chronic inflammation and an unhealthy gut microbiome, that contribute to cancer.” - Moffitt Cancer Center epidemiologist Dr. Kathleen Egan. (Link to article)

The connection between obesity and an increased risk of cancer is highly complex and not entirely understood. The risk of cancer increases with the more excess weight a person gains and the longer a person is overweight.

There are, however, other issues that bear consideration while assessing the correlation between obesity and cancer, including the fact that the biology of fat cells and how they interact with other tissues in the body is much more informative than BMI alone.

About 10% of obese patients are metabolically healthy and approximately one-third of patients with a normal BMI are metabolically unhealthy.

There is new research trying to understand the interplay of these factors.

Generally, based on epidemiological data and scientific research, it is thought that in obese people:

Excess fat tissue creates an environment in the body that can result in chronic low-level inflammation. This pro-inflammatory state results in the elevation of certain proteins called cytokines, such interleuken-6 (IL-6) and tumor necrosis factor α (TNFα), which are produced at higher levels as compared to people who are not obese.
This chronic inflammatory state results in changes to the cellular microenvironment, including DNA mutations, which may result in uncontrolled cell growth and the formation of tumors.
Excessive fat tissue can alter the production of hormones, especially estrogen and insulin, that raise cancer risk.
This has been studied quite in detail in the case of breast cancer. Before menopause, most estrogens in the body are produced in the ovaries. After menopause, the ovaries no longer produce much estrogen, and estrogens mainly come from fat tissue.
Fat tissue contains an enzyme called aromatase that converts hormones called androgens (made mostly in the adrenal glands) to estrogens.
So, heavier women have higher blood estrogen levels than leaner women. Women with higher estrogen levels have an increased risk of breast and uterine cancer compared to women with lower estrogen levels.
Higher levels of insulin may increase the risk of colorectal, kidney, and other cancers.
Fat cells can directly affect hormones or proteins that regulate cell growth and division. This may cause cells to divide and grow out of control, eventually forming tumors.
We also know that carrying excess fat, particularly around the abdomen [called visceral fat], is associated with metabolic and hormonal disorders, including insulin resistance, which may be related to cancer development.
Obesity may also weaken T-cells found near tumor cells by altering their metabolism. These changes alter the immune cells’ ability to attack and kill cancer cells.

The next blog will talk about changing your diet to decrease your cancer risk and maintain a healthy weight.