Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Large study documents how p53 mutations link to high-grade breast cancer, poor outcomes

21.04.2009
In what is believed to be the largest study of its kind in the US, researchers have found that almost 26 percent of women studied who have breast cancer have mutations in a gene important in controlling cell growth and death, and that patients with mutations in this gene – known as p53 - had poorer outcomes including a significantly increased risk of death from the cancer.

Researchers say their study, presented at the Annual Meeting of the American Association for Cancer Research (AACR), confirm the findings of other smaller studies, and is an important step forward in understanding risk factors that lead to development of breast cancer.

For example, the investigators have found that postmenopausal women with high body weight were more likely to have a particular kind of p53 mutation, but they say this link needs to be studied further.

"The p53 gene is the guardian of the genome because it signals the cell to repair DNA damage when that occurs. If we can find genetic or environmental risk factors that lead to damage of p53 or stress on the gene, we may be able to help prevent development of breast cancer as well as other cancers," says the study's lead investigator, Catalin Marian, MD, PhD, a research instructor of cancer genetics and epidemiology at the Lombardi Comprehensive Cancer Center at Georgetown University Medical Center (GUMC).

The work was conducted by research groups led by Peter Shields, MD, professor of medicine and oncology at Lombardi, and Jo Freudenheim, PhD, chair of social and preventive medicine at the State University of New York at Buffalo.

Scientists from both institutions are evaluating data from a population-based case-control study of breast cancer in New York. The Western New York Exposure and Breast Cancer (WEB) Study included 1,170 women diagnosed with breast cancer between 1996 and 2001 as well as 2,116 women without cancer, and is an effort to link lifestyle and environmental exposures to gene changes and development of breast cancer. In this part of the study, GUMC researchers isolated DNA from 803 breast cancer tumor samples, and screened them for DNA mutations in the p53 gene. They found the p53 mutation frequency among the cases to be 25.6 percent, and 95 percent of those were point mutations – a change in a single base nucleotide with another nucleotide.

They determined that a p53 mutation was most commonly associated with ER-/PR- tumors in premenopausal women, but among postmenopausal women with breast cancer, the presence of a p53 mutation was most commonly associated with higher body mass index (BMI), and higher-grade, poorly differentiated tumors. Women with these tumors as well as p53 mutations had a 2.4-fold increased risk of dying from their disease, Marian says.

The researchers then dug a little deeper to see if tumor status was related to the type of point mutation found in the p53 gene. There are four nucleotides in the genome and they come in two complementary pairings – A and G are purines and C and G are pyrimidines. A transition mutation occurs when one purine is replaced by the other purine or when pyrimidines are switched. A transversion mutation is replacement of a purine with a pyrimidine or vice versa and is considered to be "more dangerous, with a higher chance of negatively affecting the function of the p53 protein," Marian says.

While either transition or transversion mutations were found in premenopausal with hormone receptor-negative cancer, only transition mutations (A or G replaced by each other) were positively associated in postmenopausal women with hormone receptor-negative cancers that were higher-grade and had a poorer outcome. Transversion mutations (A or G replaced by C or G or vice versa) in postmenopausal women with breast cancer were associated with a higher BMI.

"The association between transversions and BMI is particularly interesting, because excess body weight is already known to be a risk factor for breast cancer," Marian says.

"We are laying the groundwork for future studies that look at gene-gene and gene-environmental interactions with p53," he says. "If we can document such effects, it may be possible to test patients for these factors in advance and tailor treatment appropriately."

Marian and his co-authors report no potential financial conflicts. This work was funded by the Department of Defense Breast Cancer Research Program and the National Institutes of Health.

About Lombardi Comprehensive Cancer Center

The Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center and Georgetown University Hospital, seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Lombardi is one of only 41 comprehensive cancer centers in the nation, as designated by the National Cancer Institute, and the only one in the Washington, DC, area. For more information, go to http://lombardi.georgetown.edu.

About Georgetown University Medical Center

Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through our partnership with MedStar Health). Our mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis -- or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing and Health Studies, both nationally ranked, the world-renowned Lombardi Comprehensive Cancer Center and the Biomedical Graduate Research Organization (BGRO), home to 60 percent of the university's sponsored research funding.

Karen Mallet | EurekAlert!
Further information:
http://www.georgetown.edu

More articles from Studies and Analyses:

nachricht The Great Unknown: Risk-Taking Behavior in Adolescents
19.01.2017 | Max-Planck-Institut für Bildungsforschung

nachricht A sudden drop in outdoor temperature increases the risk of respiratory infections
11.01.2017 | University of Gothenburg

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Quantum optical sensor for the first time tested in space – with a laser system from Berlin

For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.

According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

New technology for mass-production of complex molded composite components

23.01.2017 | Process Engineering

Quantum optical sensor for the first time tested in space – with a laser system from Berlin

23.01.2017 | Physics and Astronomy

The interactome of infected neural cells reveals new therapeutic targets for Zika

23.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>