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!
Rutgers-led innovation could spur faster, cheaper, nano-based manufacturing
14.02.2018 | Rutgers University
New study from the University of Halle: How climate change alters plant growth
12.01.2018 | Martin-Luther-Universität Halle-Wittenberg
An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.
The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.
In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...
19.03.2018 | Event News
16.03.2018 | Event News
13.03.2018 | Event News
22.03.2018 | Trade Fair News
22.03.2018 | Earth Sciences
22.03.2018 | Earth Sciences