Obesity-driven Endometrial Cancer Raises Need for Intervention

In women, the association between obesity and endometrial cancer is stronger than in any other type of cancer.¹ Recent analyses predict a 55% increase in endometrial cancer rates from 2010 to 2030.²

“Obesity results in a state of increased estrogen, which drives the cells of the lining of the uterus to grow and divide. In addition, the ‘brakes’ are also not working as well in obese women. The ‘brakes’ are from progesterone, which is lower in obese women,” said Karen H. Lu, MD, J. Taylor Wharton distinguished chair in gynecologic oncology at The University of Texas MD Anderson Cancer Center in Houston, in an interview with Cancer Therapy Advisor.

The increased levels of estrogen in obese women causes increased cellular proliferation and increased double-stranded DNA breaks, resulting in DNA instability and mismatch repair defects.

“Some estrogen metabolites are also known to be genotoxic. The more frequently endometrial cells divide, the greater the accumulation of genetic mutations, which can ultimately result in neoplastic transformation,” continued 1 of the review’s co-authors, Rosemarie E. Schmandt, PhD, an associate professor at the department of gynecologic oncology and reproductive medicine at MD Anderson Cancer Center.

“This is particularly relevant in women with Lynch syndrome, who lack certain DNA repair mechanisms, and are more likely to acquire early, deleterious mutations in the endometrium, which lead to cancer.”

“Obesity is associated with elevated levels of insulin, IGF-1, and glucose levels, all of which promote endometrial growth and fuel endometrial cancer progression,” explained Dr Schmandt.