About one-third of adults in the U.S. are obese. While the risks of diabetes and cardiovascular disease in these individuals have long been known, obesity also carries a significantly higher risk of cancer. Researchers are still delving into why this is so.

The “why” of the obesity-cancer link is what Manjula Gupta, PhD, and Ofer Reizes, PhD, both from the Cleveland Clinic Foundation, will address in their Short Course, Obesity and Cancer (72223), offered at the 68th AACC Annual Scientific Meeting & Clinical Lab Expo on August 1 from 2:30 p.m. – 4 p.m.

CLN Stat talked with Gupta about the underlying mechanisms that increase the risk of cancer in obese people.

The relationship, she said, begins with higher amounts of dysfunctional adipose tissue. “In addition to lipid storing capacity, adipose tissue is a highly active endocrine organ made of various cell types such as adipocytes, preadipocytes, fibroblasts, and macrophages.”

People who are obese have higher and more active levels of adipocytes, which secrete various cancer-promoting bioactive molecules known as adipokinins (leptin, adiponectin) and cytokines (TNFα and IL-6), Gupta explained. This, in turn, leads to increased leptin production, which promotes cell proliferation via leptin receptors expressed in cancer stem cells.

Meanwhile, adiponectin, which has insulin-sensitizing effects in liver and skeletal muscles and antiproliferative effects, is less abundant in obese people. This, in turn, contributes to insulin resistance and allows unchecked growth of cancer cells, according to Gupta.

Other contributors to insulin resistance, she said, include increased free fatty acids and the inflammatory effects of cytokines. This leads to higher levels of insulin-like growth factor-1, which promotes cancer development and growth.

Other underlying mechanisms of the cancer/obesity duet include increased aromatase expression, which boosts estradiol levels and promotes the growth of estrogen-dependent cancers; and enhanced chronic inflammation and oxidative stress, which also contributes to the higher risk of cancer.

There are several promising lines of research in this area, she said. For instance, a greater understanding of the molecular mechanisms of leptin and adiponectin and their interplay with insulin resistance offers the prospect of new therapeutic approaches targeting signaling pathways.

After attending this session, Gupta said, participants will understand the metabolic consequences of obesity, including the pro-carcinogenic effects and molecular mechanisms of leptin, be able to identify the markers of insulin resistance and describe how they contribute to an increased risk of cancer.