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!
New study: How does Europe become a leading player for software and IT services?
03.04.2017 | Fraunhofer-Institut für System- und Innovationsforschung (ISI)
Reusable carbon nanotubes could be the water filter of the future, says RIT study
30.03.2017 | Rochester Institute of Technology
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...
For the first time, scientists have succeeded in studying the strength of hydrogen bonds in a single molecule using an atomic force microscope. Researchers from the University of Basel’s Swiss Nanoscience Institute network have reported the results in the journal Science Advances.
Hydrogen is the most common element in the universe and is an integral part of almost all organic compounds. Molecules and sections of macromolecules are...
22.05.2017 | Event News
17.05.2017 | Event News
16.05.2017 | Event News
22.05.2017 | Materials Sciences
22.05.2017 | Life Sciences
22.05.2017 | Physics and Astronomy