Why men are more prone to liver cancer

Jan 15, 2008

A fundamental difference in the way males and females respond to chronic liver disease at the genetic level helps explain why men are more prone to liver cancer, according to MIT researchers.

“This is the first genome-wide study that helps explain why there is such a gender effect in a cancer of a nonreproductive organ, where you wouldn't expect to see one,” said Arlin Rogers, an MIT experimental pathologist and lead author of a paper that appeared last month in the journal Cancer Research.

Men develop liver cancer at twice the rate of women in the United States. In other countries, especially in Asia, the rate for men can be eight or 10 times that for women.

Liver cancer is the fifth most common cancer in the world and the third-biggest killer. Rates in the United States are lower than those in other countries but are rising rapidly, in part due to high hepatitis C infection rates during the 1970s from blood transfusions and IV drug abuse. Obesity and type 2 diabetes are additional risk factors of current concern.

“It's an epidemic waiting to happen,” said Rogers, a principal research scientist in MIT's Division of Comparative Medicine.

Male and female livers are inherently different, with most of the differences arising during puberty when male livers are exposed to periodic bursts of growth hormone. This prompts male livers to express different genes than female livers, which explains why men and women can have different reactions to certain antibiotics and other medications.

The MIT team studied mice, which also have higher liver cancer rates among males. The mice were infected with Helicobacter hepaticus, which produces the same hepatitis symptoms characteristic of human hepatitis B and C.

In humans and mice, healthy males and females both can respond to acute toxins and other stresses. But the male liver is less well equipped to cope with the chronic inflammation induced by certain infectious agents.

When the male mice developed chronic hepatitis, some masculine liver genes were upregulated and others turned off. At the same time, some feminine genes were reactivated. This resulted in an unpredictable gene profile termed “liver-gender disruption.”

“There's no rhyme or reason to it. There's just a complete scrambling of masculine and feminine genes,” said Rogers.

When the researchers mapped the sex-specific genes, they found intimate associations with inflammatory pathways. In males with chronic hepatitis, some gender-specific genes were overexpressed and others underexpressed, the liver was unable to maintain normal metabolic function and cancer emerged in a significant number of the animals.

The authors propose that adult females are less vulnerable to liver-gender disruption because there is no requirement for the active signaling needed to maintain a masculine gene profile. Because the female liver follows the “default” developmental pathway, a greater disturbance is required to initiate the cancer process, said Rogers.

The researchers had expected that castrating male mice at one year of age when they had chronic hepatitis, but not cancer, would have a protective effect. They also gave some mice a powerful androgen to see if that would promote tumors. Neither treatment had any effect, demonstrating that male sex hormones such as testosterone do not directly promote liver cancer in adults.

These results could be relevant to cancers of other organs, such as the stomach and colon, which also are associated with chronic inflammation and are more common in men.

“This study was a collaboration between the Division of Comparative Medicine and Center for Environmental Health Sciences. It would not have been possible without the expertise and team-oriented philosophy of the wonderful scientists we have here,” said Rogers.

Source: Massachusetts Institute of Technology

Explore further: Quarter of prostate cancer patients may abandon 'watchful waiting' approach

add to favorites email to friend print save as pdf

Related Stories

Hepatitis C-like viruses identified in bats and rodents

Apr 22, 2013

As many as one in 50 people around the world is infected with some type of hepacivirus or pegivirus, including up to 200 million with hepatitis C virus (HCV), a leading cause of liver failure and liver cancer. There has been ...

Most detailed picture ever of key part of hepatitis C

Nov 28, 2013

Scientists at The Scripps Research Institute (TSRI) have determined the most detailed picture yet of a crucial part of the hepatitis C virus, which the virus uses to infect liver cells. The new data reveal ...

Recommended for you

Unraveling the 'black ribbon' around lung cancer

12 hours ago

It's not uncommon these days to find a colored ribbon representing a disease. A pink ribbon is well known to signify breast cancer. But what color ribbon does one think of with lung cancer?

User comments : 0

More news stories

Turning off depression in the brain

Scientists have traced vulnerability to depression-like behaviors in mice to out-of-balance electrical activity inside neurons of the brain's reward circuit and experimentally reversed it – but there's ...

Hackathon team's GoogolPlex gives Siri extra powers

(Phys.org) —Four freshmen at the University of Pennsylvania have taken Apple's personal assistant Siri to behave as a graduate-level executive assistant which, when asked, is capable of adjusting the temperature ...

Better thermal-imaging lens from waste sulfur

Sulfur left over from refining fossil fuels can be transformed into cheap, lightweight, plastic lenses for infrared devices, including night-vision goggles, a University of Arizona-led international team ...