Why men are more likely to develop liver cancer

Why men are more likely to develop liver cancer

Researchers discovered that a hormone secreted by fat cells that is present at higher levels in women can stop liver cells from becoming cancerous. The study, which will be published in the Journal of Experimental Medicine, helps explain why hepatocellular carcinoma (HCC) is more common in men, and could lead to new treatments for the disease.

In the United States, men are twice as likely as women to develop HCC. A potential contributor to this gender disparity is adiponectin, a hormone secreted by fat cells that helps control the body's metabolism. According to the Cancer rates in Spain report published by the Spanish Medical Oncology Society (SEOM, in its Spanish initials), there are an estimated 5862 patients with liver cancer in Spain (4252 men and 1610 women). In line with other European Union countries, this corresponds to approximately 12 out of every 100,000 men and 3.5 out of every 100,000 women.

 "Circulating adiponectin levels have been reported to be higher in women than in men," explains the author. "However, adiponectin's role in HCC is controversial and needed further investigation."

Similar to humans, male mice are more prone to HCC than females. Researchers found that increased levels of adiponectin in female mice protect them from HCC. The researchers determined that the hormone activates two proteins inside liver cells, known as p38? and AMPK, that block cell proliferation and impair tumor growth.

Inhibiting testosterone production in male rodents increased their adiponectin levels and reduced tumor growth. The authors found that testosterone activates a protein in fat cells called JNK1 that inhibits adiponectin production.

"Our results unravel a clear crosstalk between sex hormones, adipose tissue, and the liver, clarifying the mechanism underlying gender disparity in liver cancer development," the senior author says.
Intriguingly, adiponectin levels are also reduced in obesity, another major risk factor for HCC. The study also suggests that adiponectin and metformin--a common antidiabetic drug that activates AMPK--could be used as novel treatments for liver cancer.