Navigation Links
New clues may link hereditary cancer genes to increased risk of cancer from alcohol
Date:1/23/2014

In laboratory experiments conducted on human cell lines at the Johns Hopkins Kimmel Cancer Center, scientists have shown that people carrying certain mutations in two hereditary cancer genes, BRCA2 and PALB2, may have a higher than usual susceptibility to DNA damage caused by a byproduct of alcohol, called acetaldehyde.

The scientists say they suspect that the two genes in their normal forms evolved to protect cells against the damaging effects of acetaldehyde, which can lead to cancer.

While the scientists caution that the research is preliminary, they say their findings suggest that studies on disease risk factors should take into account these particular genetic variations and the use of alcohol.

"We need to identify which behaviors in certain populations increase disease risk, and keep in mind that our genetic susceptibility plays a large role in cancer risk," says Scott Kern, M.D ., the Everett and Marjorie Kovler Professor in Pancreas Cancer Research at Johns Hopkins.

Acetaldehyde (pronounced ah-set-AL-deh-hide) is produced during the metabolism of alcohol and is known to cause DNA damage. Scientists say the chemical is ubiquitous in nature, found in many sources, including apples and gut bacteria, and is responsible for the "hangovers" people experience after heavy alcohol use. Alcohol use has long been linked to cancers of the upper aerodigestive tract, breast, pancreas, and stomach.

After reading reports linking acetaldehyde and a related chemical, formaldehyde, to a rare cancer-susceptibility disease called Fanconi anemia (which is characterized by mutations in BRCA2 and other genes), Kern and his team took a closer look at the growth response of cells exposed to acetaldehyde and other compounds. The team created human cell lines that lacked BRCA2 and PALB2 genes.

"You can add any chemical to a cell culture and growth of the cells will go down, so the significant responses are ones that differ by 10-fold or larger," says Kern.

The scientists found that BRCA2 and PALB2-mutant cell lines exposed to acetaldehyde had up to 25 times more growth reduction when compared with related cells lacking these mutations. The significant reduction in cell growth indicates that these cell lines, which lack the two genes, are more susceptible to the DNA damage caused by acetaldehyde, say the scientists. They suggest that the DNA-damaging effects of acetaldehyde exposure in people lacking these genes may accelerate cancer growth.

Kern and his team estimated that the BRCA2 and PALB2 genes, when they function normally, protect cells against up to 96 percent of the toxicity associated with acetaldehyde. Results of the experiments are published in the January 2014 issue of the American Journal of Pathology.

Kern says that the acetaldehyde model could, theoretically, be used to develop drugs that kill cancer cells, as well as to alter cancer risk. They found that cell lines with mutations in PALB2 were up to 20 percent more sensitive to chemotherapy agents, such as cisplatin, that work by breaking down DNA, compared with anticancer drugs that work in other ways.

When the genes function correctly, BRCA2 and PALB2 bind to each other to repair DNA damage. Mutations in the genes disable their DNArepairing capability and make carriers more susceptible to cancer, the researchers say.

"BRCA2 and PALB2 may have evolved over time to repair or protect us from acetaldehyde damage," says Kern. "In most people, the genes function well and we're equipped to handle most of our exposure to acetaldehyde, but patients or carriers with mutations in these genes could face a higher risk of cancers with high exposure to alcohol or acetaldehyde-containing foods."

Kerns says that there is a possibility acetaldehyde leaves a signature of damage in cells. He adds that scientists may have been overlooking the role of acetaldehyde in disease and aging.


'/>"/>

Contact: Vanessa Wasta
wasta@jhmi.edu
410-614-2916
Johns Hopkins Medicine
Source:Eurekalert

Related medicine news :

1. Stem cells offer clues to reversing receding hairlines
2. Clues to cocaines toxicity could lead to better tests for its detection in biofluids
3. Thomas Jefferson University Kimmel Cancer Center: Researchers Find New Clues to Treat Rare and Aggressive Inflammatory Breast Cancer
4. Scientists find potential new clues for identifying breast cancer risk
5. Alligator Study Gives Clues to Regrowing Lost Teeth
6. Scientists Discover More Genetic Clues to Testicular Cancer
7. Dog DNA May Yield Clues to Human Eczema
8. New genetic clues to breast and ovarian cancer
9. Mast cells give clues in diagnosis, treatment of dengue
10. Virus-like particles provide vital clues about brain tumors
11. Skin deep: Fruit flies reveal clues to wound healing in humans
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/24/2017)... ... February 24, 2017 , ... ... Senior International Elite division on February 12th. Ms. Esparza qualified into this ... elite qualifier competition held in Las Vegas, Nevada. Frida is one of approximately ...
(Date:2/23/2017)... ... 23, 2017 , ... On February 22, 2017 the U.S. ... to withdraw previous guidance issued by the Obama Administration requiring schools to treat ... 2016 by the Obama Administration came in response to a growing number of ...
(Date:2/23/2017)... ... February 23, 2017 , ... Rare ... audience, will be participating in Rare Disease Day events, hosted by the Rare ... Rare Disease Report, a website, weekly e-newsletter and quarterly publication, will be conducting ...
(Date:2/23/2017)... ... February 23, 2017 , ... Hamlin Dental Group and Dr. Hamid ... sponsoring a raffle. Throughout the month of February, patients who visit Hamlin Dental Group ... for a dinner for two at the Cheesecake Factory. , Tickets are available ...
(Date:2/23/2017)... ... February 23, 2017 , ... On April 13, 2017, ... “Doping in Sport: How the Culture Might Change,” in conjunction with ... symposium will be held at Pepperdine University in Malibu, California. , Sir Philip ...
Breaking Medicine News(10 mins):
(Date:2/23/2017)... , Feb. 23, 2017  Genesis Healthcare Services has ... announcement was made by Bill Monast , President ... and Nathan Feltman , executives with Home ... Services, LLC. This acquisition helps Hospice ... of technology enabled durable medical equipment (DME) solutions for ...
(Date:2/23/2017)... 23, 2017  Cogentix Medical, Inc. (NASDAQ: CGNT), a ... proprietary products for the urology market, will release financial ... December 31, 2016 before the market open on Thursday, ... host a conference call and webcast to discuss its ... 2017 at 11:00 a.m. Eastern Time (10:00 a.m. Central ...
(Date:2/23/2017)... Calif., Feb. 23, 2017 Nevro Corp. (NYSE: NVRO), ... solutions for the treatment of chronic pain, today reported financial ... 31, 2016. 2016 Accomplishment & Highlights: ... year 2016, an increase of 228% as reported, over the ... 2016, an increase of 612% over the prior year ...
Breaking Medicine Technology: