Navigation Links
MIT: Why men are more prone to liver cancer
Date:1/15/2008

CAMBRIDGE, Mass.--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.


'/>"/>

Contact: Elizabeth Thomson
thomson@mit.edu
617-258-5402
Massachusetts Institute of Technology
Source:Eurekalert

Related biology news :

1. The importance of mangrove conservation in tsunami prone regions
2. Carnegie Mellon scientists develop nanogels that enable controlled delivery of carbohydrate drugs
3. Clearance of hepatitis C viral infection after liver transplantation
4. Targeting nerve growth factor may cure liver cancer
5. Mountain pine beetle: Canadas new government delivers
6. Using green chemistry to deliver cutting-edge drugs
7. Mixing large doses of both acetaminophen painkiller and caffeine may increase risk of liver damage
8. Jumping genes could make for safer gene delivery system
9. Nanoengineers mine tiny diamonds for drug delivery
10. Computer solution to delivery problem
11. Genetic ancestral testing cannot deliver on its promise, study warns
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/12/2016)... 2016 WearablesResearch.com , a brand of ... results from the Q1 wave of its quarterly wearables ... consumers, receptivity to a program where they would receive ... insurance company. "We were surprised to see ... Michael LaColla , CEO of Troubadour Research, "primarily because ...
(Date:4/28/2016)... April 28, 2016 First quarter 2016:   ... 966% compared with the first quarter of 2015 The ... 589.1 M (loss: 18.8) and the operating margin was 40% (-13) ... Cash flow from operations was SEK 249.9 M (21.2) ... guidance is unchanged, SEK 7,000-8,500 M. The operating margin ...
(Date:4/15/2016)... CHICAGO , April 15, 2016  A ... companies make more accurate underwriting decisions in a ... offering timely, competitively priced and high-value life insurance ... health screenings. With Force Diagnostics, rapid ... and lifestyle data readings (blood pressure, weight, pulse, ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... DIEGO , June 24, 2016 ... more sensitively detects cancers susceptible to PARP inhibitors ... circulating tumor cells (CTCs). The new test has ... HRD-targeted therapeutics in multiple cancer types. ... targeting DNA damage response pathways, including PARP, ATM, ...
(Date:6/23/2016)... , ... June 23, 2016 , ... ... release of its second eBook, “Clinical Trials Patient Recruitment and Retention Tips.” Partnering ... retention in this eBook by providing practical tips, tools, and strategies for clinical ...
(Date:6/23/2016)... 2016 /PRNewswire/ - FACIT has announced the creation ... biotechnology company, Propellon Therapeutics Inc. ("Propellon" or "the ... a portfolio of first-in-class WDR5 inhibitors for the ... WDR5 represent an exciting class of therapies, possessing ... for cancer patients. Substantial advances have been achieved ...
(Date:6/23/2016)... ... June 23, 2016 , ... Charm Sciences, Inc. ... test has received AOAC Research Institute approval 061601. , “This is another AOAC-RI ... stated Bob Salter, Vice President of Regulatory and Industrial Affairs. “The Peel Plate ...
Breaking Biology Technology: