Genes key to high liver cancer rates in men

"A fundamental difference in the way men and women 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.

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