Archive for July, 2010

Genome Sequencing Reveals How Breast Cancer Spreads

Tuesday, July 27th, 2010

Genetic analysis of a woman with breast cancer has yielded important information about an extremely dangerous type of breast cancer that largely affects blacks and younger women, say U.S. researchers.

By comparing three genomes — the genome of a 44-year-old black woman who had “triple negative” breast cancer and the genomes of her breast tumor and a metastatic tumor that developed in her brain — the scientists identified 20 genetic changes in a subset of breast tumor cells that probably played a role in the spread of the cancer that led to her death within a few months.

The findings suggest that sequencing entire genomes of cancer patients, along with the genomes of their primary and metastatic tumors, could improve understanding of how tumors spread and possibly lead to the development of new drugs that target important cancer-causing genetic errors, according to the researchers, from the Washington University School of Medicine in St. Louis.

“We are getting an intimate look at the lethal spread of a breast cancer, which is now possible because we can sequence entire genomes quickly at reasonable cost,” Elaine Mardis, co-director of the university’s Genome Center and the study’s senior author, said in a university news release.

“This work lays the foundation for understanding the genetic basis of tumor progression and metastasis and for identifying new drug targets that can improve the outlook for women with this disease,” she added.

The study is published in the issue of Nature.

Job Stress Might Actually Help You Smoke Less

Tuesday, July 20th, 2010

Work stress may actually lower smokers’ nicotine dependence, finds a study that contradicts the popular belief that job pressures boost levels of smoking.

German researchers used an internationally recognized and validated nicotine dependence test to assess the smoking habits of 197 employed participants in the Cologne Smoking Study.

The study found that workers who experience job-related stress are likely to smoke less than they normally would, and so have a lower dependence on nicotine. Long working hours and strict company smoking rules may explain the unexpected findings.

“Heavy workload may drive employees to smoke only in their spare time,” study leader Anna Schmidt, of the University of Cologne, said in a news release.

The researchers also found that nicotine dependence was less likely among people who were married, religious and had a higher level of education.

The study was published in the journal Tobacco Induced Diseases.

New Alzheimer’s Gene Identified

Tuesday, July 13th, 2010

Researchers have pinpointed a gene variant that nearly doubles the risk of developing late-onset Alzheimer’s disease, a new study says.

A U.S. research team examined gene variations across the human genome, or full DNA sequence, of 2,269 people with late-onset Alzheimer’s and 3,107 people without the disease. This research — known as a genome-wide association study — looks throughout the entire genome for small differences, or variants, in long stretches of DNA that are more prevalent in those with a particular disease or condition.

About 9 percent of those with late-onset Alzheimer’s had a specific variation in the gene MTHFD1L on chromosome 6, according to the study. Only about 5 percent of those who did not have Alzheimer’s had the variant.

Late-onset Alzheimer’s, which affects those 60 and up, is the most common form of the brain disorder.

With the number of people with Alzheimer’s expected to nearly double from 18 million worldwide to 34 million by 2025, according to the World Health Organization, researchers have been hunting for genes that play a role in Alzheimer’s disease. The hope is that understanding the function of the genes could help in developing better treatments, which are sorely lacking.

So far, the primary known genetic contributor to late-onset Alzheimer’s is a variant of the gene APOE on chromosome 19. The Alzheimer’s-linked APOE variant occurs in about 40 percent of people who develop late-onset Alzheimer’s, while about 25 to 30 percent of the general population has it, according to the National Institute on Aging.

The influence of the MTHFD1L variation is not as strong as APOE, and the variation itself is not as common in the population, said principal investigator Margaret Pericak-Vance, director of the University of Miami Miller School of Medicine’s John P. Hussman Institute for Human Genomics.

But what makes the current finding so interesting is how it might connect to previous research about MTHFD1L. The gene is involved with the metabolism of folate, which in turn can influence levels of homocysteine.

Elevated homocysteine, which is often tied to folic acid deficiencies in the diet, have been shown to be a risk factor for coronary artery disease and late-onset Alzheimer’s.

Previous genome-wide studies have also implicated another variation in MTHFD1L in coronary artery disease.

Taken together, the research hints at ways in which the gene variant might be associated with changes in blood vessel function in the brain that impact Alzheimer’s, Pericak-Vance said.

“The key reason people are excited about this is that it melds the genetics and the biology,” Pericak-Vance said. “Maybe we can put the biology together with genetics and come up with some way to either treat it or approach it.”

While lots of genetic variants have been singled out as possible contributors to Alzheimer’s, the findings often can’t be replicated or repeated, leaving researchers unsure if the results are a coincidence or actually important, said Dr. Ron Peterson, director of the Mayo Alzheimer’s Disease Research Center in Rochester, Minn.

“The strength of his study is it includes a large number of subjects, they looked at a large number of [DNA sequence variations], and they replicated previously reported findings, which gives you confidence that they are correct,” Peterson said.

The study is slated to be presented at the American Academy of Neurology’s meeting in Toronto.

Study Offers Insights Into Male Pattern Baldness

Tuesday, July 6th, 2010

Researchers are reporting that they’ve linked a gene to a rare condition that makes people develop thin “peach fuzz” hair, potentially paving the way toward greater insight into male-pattern baldness.

The finding won’t immediately lead to a better treatment or cure, said Angela M. Christiano, co-author of the study, published April 15 in the journal Nature. And though it’s “just a tiny little piece of the puzzle,” it could provide perspective about a component of male-pattern baldness known as shrinkage, said Christiano, director of the Center for Human Genetics at Columbia University.

Contrary to popular belief, male-pattern baldness doesn’t cause hair to stop growing. Instead, hair still grows but it’s short and fine, like peach fuzz, Christiano said.

“If you look at a very bald scalp, they are still making tiny little peach-fuzz hairs,” she said. “A follicle is still there. The hardware is still there to grow a hair of some kind.”

People with a rare condition called hereditary hypotrichosis simplex have the same problem, although it begins at birth.

In the new study, Christiano and her colleagues examined the genetic makeup of members of two Pakistani families and one Italian family whose members have inherited the condition. The researchers discovered a gene in which a mutation appears to cause the problem.

The gene, called APCDD1, is located in a region of chromosome 18 that has been shown in previous studies to be linked to other forms of hair loss. The researchers also found that APCDD1 inhibits a signaling pathway that has long been shown to control hair growth in mice, but has not been extensively linked to human hair growth.

In addition to providing more insight into hereditary hypotrichosis simplex, the gene research “gives us an inroad into understanding male-pattern baldness” because the conditions are similar, Christiano said. It may be a matter of reprogramming the hair software because the hardware is still there, she said.

Part of the challenge of studying baldness is that mice don’t suffer from the equivalent of male-pattern baldness, making animal research less effective in understanding how hair growth works, she said.

Dr. Doris Day, a dermatologist in New York City, said that about half of people older than 50 have hair loss. “It can be debilitating, especially to women, who have fewer options for treatment,” Day said.

Drugs such as Rogaine and Propecia treat baldness, but they do so by preventing future hair loss rather than growing new hair, Christiano said.

Also, Day said, the medications have side effects. “Most of the drugs block hormones or enzymes,” she said. “However, they are not specific to the scalp so side effects can include decreased libido as well as potential damage to the liver.”

“The medications need to be taken indefinitely in order to remain effective,” she said, “and for some people, the medications do not adequately control the hair loss.”

A gene-based treatment, by contrast, might allow hair to grow normally. And understanding the genetic basis of baldness could help researchers find better treatments for other conditions, such as alopecia, which causes hair loss, Christiano said, adding that she has alopecia.

SOURCES: Angela M. Christiano, Ph.D., director, Center for Human Genetics, Columbia University Medical Center, New York City; Doris Day, M.D., dermatologist, New York City;