Gender Disparity in Liver Cancer May Be Due to Estrogen-mediated Inhibition
of Interleukin 6
Hepatocellular carcinoma (HHC),the most common form of liver
cancer, is a possible long-term outcome
of chronic infection with hepatitis B virus (HBV)
or hepatitis C virus (HCV), as well as other
causes of chronic liver disease such as heavy alcohol use.
HCC
occurs mainly in men (who have 3-5 times the risk of women), and a similar disparity
by sex is seen in mice given a chemical carcinogen that causes liver cancer, diethylnitrosamine (DEN). As reported in the July 6, 2007
issue of Science, researchers examined
a possible mechanism underlying this sex disparity.
Results
·In studies
in mice, DEN administration caused greater increases in serum interleukin-6 (IL-6)
concentrations in males than it did in females.
·Ablation
of IL-6 abolished the sex differences in development of liver cancer.
·DEN exposure
promoted production of IL-6 in Kupffer cells in a manner
dependent on the Toll-like receptor adaptor protein MyD88, ablation of which also
protected male mice from DEN-induced hepatocarcinogenesis.
·Estrogen
inhibited secretion of IL-6 from Kupffer cells exposed
to necrotic hepatocytes and reduced circulating concentrations
of IL-6 in DEN-treated male mice.
Conclusion
By
suppressing one inflammatory response pathway, estrogen may help prevent the injury
and excessive cell proliferation that can lead to HCC.
Based
on these results, the authors wrote, “We propose that estrogen-mediated inhibition
of IL-6 production by Kupffer cells reduces liver cancer
risk in females, and these findings may be used to prevent HCC in males.”
University
of California, San Diego, CA; Life Foundation, Tokyo, Japan; Newcastle University,
Newcastle Upon Tyne, UK.
7/20/07
Reference WE Naugler, T Sakurai, S Kim, and
others.Gender disparity in liver cancer due to
sex differences in MyD88-dependent IL-6 production.Science 317(5834):
121-124. July 6, 2007.
