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!
Multi-year study finds 'hotspots' of ammonia over world's major agricultural areas
17.03.2017 | University of Maryland
Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing
17.03.2017 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
29.03.2017 | Materials Sciences
29.03.2017 | Physics and Astronomy
29.03.2017 | Earth Sciences