New Genetic Clues to Ovarian Cancer

Study Suggests Genetic Mutations May Be Linked to Ovarian Cancer

June 29, 2011 -- Multiple genetic mutations appear to be involved in the development of ovarian cancer, according to a new large-scale analysis of tumor samples.

Researchers from the Cancer Genome Atlas Research Network looked at 489 high-grade serous ovarian adenocarcinomas (HGS-OvCa). These are a kind of epithelial ovarian cancer, the most common kind.

Ovarian cancer is the fifth-leading cause of cancer death among U.S. women, the researchers write in the journal Nature.

Nearly 22,000 new cases were found in the U.S. in 2010, according to estimates. Nearly 14,000 U.S. women died from the cancer last year, the researchers report.

After analyzing the samples, the researchers found that mutations in a gene known as TP53 predominated. It was found in 96% of the tumor samples.

However, the researchers found mutations in nine other genes, including NF1, BRCA1 and BRCA2, RB1, and CDK12. BRCA1 and BRCA2 were mutated in 22% of the samples. The other seven mutated genes identified were only found in 2% to 6% of the samples.

''The mutation spectrum marks HGS-OvCa as completely distinct from other ovarian cancer histological subtypes," the researchers write.

Differences in survival varied by type of mutation.  For instance, those with BRCA1/2 mutated cases had higher overall survival than those with BRCA1/2 wild type.

By uncovering the genetic mutations underlying different ovarian cancer subtypes, the hope is to pave the way for better, targeted treatments.

Ovarian cancer often has vague symptoms. For that reason, the disease is often diagnosed at advanced stages.

A woman should see her doctor if she has daily symptoms of bloating, feeling full quickly, difficulty eating, or pelvic or abdominal pain for more than a few weeks.

Women ages 55 and older are at higher risk. Women who give birth earlier and have multiple children are at lower risk than those who do neither. Women with a personal history of breast cancer or a family history of breast or ovarian cancer are at increased risk of ovarian cancer.

New Genetic Clues to Cause of Parkinson's

Researchers Link 2 Genetic Variants to Parkinson's Disease

June 24, 2011 -- Researchers have identified two new genetic variants linked to Parkinson's disease and say they now know how big a role heredity plays in the neurodegenerative disorder.

About a dozen genetic associations with Parkinson's have been confirmed, and many more remain to be discovered, says researcher Nicholas Eriksson, PhD, of the California-based direct-to-consumer gene testing company 23andMe.

In their new study, published this week in the journal PLoS Genetics, Eriksson and colleagues estimated that about a quarter of the variation in susceptibility to the disease is due to genetic factors.

"Each new genetic variant we find gets us a little bit closer to being able to see the full picture of how genes impact this disease," Eriksson tells WebMD. "Roughly 10 genetic variants that contribute to Parkinson's had been found and we added another two to the list."

The exact causes of Parkinson's disease are not known, but researchers now believe that both environmental triggers and genetic influences play a role.

Genetic variants have been implicated in the small percentage of cases that occur in people under the age of 50, known as early-onset Parkinson's. But much less is known about the role of genes in late-onset disease.

In an effort to better understand genetic influences in both early- and late-onset Parkinson's, Eriksson, study researcher Chuong B. Do, PhD, and colleagues conducted a novel genome-wide study involving around 3,400 Parkinson's patients and close to 30,000 people without the disease who were 23and Me clients.

The Parkinson's patients were recruited with the help of the Michael J. Fox Foundation, the Parkinson's Institute, and the National Parkinson's Foundation. The study was funded solely by the genetic testing company, however.

Genome-wide association studies became possible following the completion of the Human Genome Project and other landmark projects around the middle of the decade, which provided tools that allow researchers to look for genetic contributions to common diseases.

These tools include computerized human genome sequence databases, human genetic variation mapping, and continuously evolving technologies that simplify the analysis of genetic variations that contribute to disease.

The newly published study included the largest Parkinson's patient group ever recruited for a genome-wide association study.

One of the newly identified genetic variants, SCARB2, is associated with a known Parkinson's disease pathway involving protein degradation.

The other, SREBF1, is not associated with any known Parkinson's pathway.

"This variant is involved in lipid metabolism," Do tells WebMD. "Its association with Parkinson's is not really clear, which is what makes it exciting because it highlights a new area to look at."

Based on their own predictive model, the researchers estimate that around 7% of the genetic variants associated with Parkinson's disease have been identified. That means that more than 90% have not.

While the genetic variants, or mutations, identified to date explain only a small percentage of Parkinson's cases, the gene studies have provided clinically relevant information, Do says.

He points out that one identified mutation is associated with a 50% lifetime risk for developing the disease.

"This one variant accounts for a very small percentage of the total disease burden, but for people who do have the variant it is quite significant," he says.

Genetic Clue to Painful Peripheral Neuropathy

Study Shows Genetic Mutation May Be a Cause of Some Cases of Peripheral Neuropathy

June 22, 2011 -- A single gene may be responsible for the pain suffered in many people diagnosed with a type of peripheral neuropathy that previously had no known cause, a study shows.

The discovery could lead to effective treatments for the disorder, which is often characterized by burning, tingling, and numbness in the hands and feet.

The study is published in the Annals of Neurology.

Peripheral nerves are any nerves located outside the spine or brain. Damage to them -- whether by injury, infection, diabetes, or other cause -- results in peripheral neuropathy.

Treating the underlying cause of peripheral neuropathy often relieves the pain. However, for nearly a third of those diagnosed with the disorder, no such underlying cause can be identified, which greatly limits treatment options.

"For millions of people, the origin of this intense pain has been a frustrating mystery," co-researcher Stephen Waxman, MD, PhD, a professor of neurobiology and of pharmacology at Yale University, says in a news release.

Now, though, Waxman and his fellow researchers at Yale, the Veterans Affairs Medical Center in West Haven, and the University Maastricht in the Netherlands believe they have found a genetic mutation that may account for as many as 30% of these mystery cases, known as idiopathic small nerve fiber neuropathy.

Twenty-eight Dutch patients were recruited for the study after being screened for any possible known causes of the disorder. Genetic analysis revealed that eight of these men had mutations in the SCN9A gene, which, the study notes, has been associated with other pain-causing disorders.

Further analysis showed that the mutation triggered hyperactivity in certain neurons, possibly leading to nerve degeneration and subsequent development of neuropathy.

"These findings will help us as clinicians to a better understanding of our patients with small fiber neuropathy and could ideally have implications for the development of future specific therapies," University Maastricht neurologist Catharina G. Faber, MD, PhD, one of study researchers, says in a news release.