Several possible mechanisms have been suggested to explain how obesity might increase the risks of some cancers.
Obese people often have chronic low-level inflammation, which can, over time, cause DNA damage that leads to cancer.
Overweight and obese individuals are more likely than normal-weight individuals to have conditions or disorders that are linked to or that cause chronic local inflammation and that are risk factors for certain cancers.
For example, chronic local inflammation induced by gastroesophageal reflux disease or Barrett esophagus is a likely cause of esophageal adenocarcinoma.
Obesity is a risk factor for gallstones, a condition characterized by chronic gallbladder inflammation, and a history of gallstones is a strong risk factor for gallbladder cancer.
Chronic ulcerative colitis (a chronic inflammatory condition) and hepatitis (a disease of the liver causing inflammation) are risk factors for different types of liver cancer.
Fat tissue (also called adipose tissue) produces excess amounts of estrogen, high levels of which have been associated with increased risks of breast, endometrial, ovarian, and some other cancers.
Obese people often have increased blood levels of insulin and insulin-like growth factor-1 (IGF-1). (This condition, known as hyperinsulinemia or insulin resistance, precedes the development of type 2 diabetes.)
High levels of insulin and IGF-1 may promote the development of colon, kidney, prostate, and endometrial cancers.
Fat cells produce adipokines, hormones that may stimulate or inhibit cell growth.
For example, the level of an adipokine called leptin, which seems to promote cell proliferation, in the blood increases with increasing body fat.
And another adipokine, adiponectin—which is less abundant in obese people than in those of normal weight—may have antiproliferative effects.
Fat cells may also have direct and indirect effects on other cell growth regulators, including mammalian target of rapamycin (mTOR) and AMP-activated protein kinase.
Other possible mechanisms by which obesity could affect cancer risk include changes in the mechanical properties of the scaffolding that surrounds breast cells and altered immune responses, effects on the nuclear factor kappa beta system, and oxidative stress