Scientists have identified a new biomarker in the blood that could help identify more women at an increased risk of breast cancer. Such women might benefit from risk-reducing measures.

In a prospective study, researchers from Imperial College London and the Human Genetics Foundation (HuGeF) in Torino, Italy, have concluded that DNA methylation levels in blood cells are associated with breast cancer risk, and could be used to identify women at increased risk of developing the disease.

DNA methylation is the process by which methyl groups are added to the DNA, modifying its function and regulating how much of a gene’s protein product gets made, something that is essential for normal cell development. The team’s findings build on a growing body of evidence suggesting that lower than normal methylation of white blood cell DNA could be predictive of a heightened breast cancer risk.

The studies analysed by the researchers took blood samples from healthy women who were then monitored for an average period of around nine years. The women who developed breast cancer during this time had a lower level of DNA methylation in their white blood cells, compared to the women who didn’t develop the disease.

The research highlights DNA methylation as a key player in our understanding of breast cancer risk – adding to a growing list of known genetic variants associated with an increased risk of the disease – which will ultimately help us refine and improve the ways we assess, and monitor, an individual’s breast cancer risk.

Whilst this research is at a very early stage, it is hoped that one day scientists could potentially be able to proactively change methylation patterns, underlining the importance of research into epigenetics.

Further studies will now be required to understand why the methylation patterns observed in blood cell DNA are linked to breast cancer risk, as this is not currently known. It is hoped that women already known to be at increased risk of developing the disease could be given a blood test to assess and monitor methylation levels in order to better understand their risk and inform decisions around preventative treatments. Imperial College London

New research into the causes of the excessive inflammation that drives multiple sclerosis has identified a faulty “brake” within immune cells, a brake that should be controlling the inflammation. This points to a potential target for developing new therapies to treat multiple sclerosis and could have important implications for other autoimmune diseases, such as the colon disease colitis and the chronic skin condition atopic dermatitis.

Further, the work has produced new research models of multiple sclerosis symptoms such as movement disorders and balance control problems that have, until now, resisted efforts to mimic them effectively in the lab. These models represent important new tools in the efforts to better understand – and eventually cure – MS and other autoimmune conditions.

The researchers determined that a mutation in the gene Nlrp12 was causing immune cells known as T cells to go haywire. Normally, the researchers determined, the protein the gene produces acts as a brake within T cells to control the inflammatory response. But a mutation in that gene disrupts the natural process and provokes severe inflammation – with effects the researchers found most intriguing.

To the researchers’ surprise, the resulting inflammation did not produce the paralysis often associated with multiple sclerosis. It did, however, produce other MS symptoms — such as movement disorders and problems with balance control – which scientists have struggled to replicate in experimental lab settings.

“It’s important to note that MS is a spectrum disorder – some patients present with paralyzing conditions and some patients don’t,” said researcher John Lukens, PhD, of the University of Virginia School of Medicine Department of Neuroscience and its Center for Brain Immunology and Glia. “Not everybody’s symptoms are the same, so this might give us a glimpse into the etiology or pathogenesis of that family of MS.”

By blocking the inflammatory response, doctors may one day be able to control the symptoms it causes, both in MS and in other diseases driven by hyperinflammation. University of Virginia

The functions of around 150 genes have been discovered by scientists across Europe in a major initiative to try to understand the part they play in disease and biology.

Since mice share 90 per cent of their genes with humans they are one of the best organisms to help us understand human genetics.  The European Mouse Disease Clinic (EUMODIC) brought together scientists from across Europe to investigate the functions of 320 genes in mice. Over half of these genes had no previously known function, and the remaining genes were poorly understood.

Over 80 per cent of the mouse lines assessed had a characteristic that provided a clue to what the missing gene’s role might be. If the mouse fails a hearing test, for example, it suggests the missing gene might have a role in hearing. In total, they carried out over 150 different tests on each mouse line.

The researchers classified 94 genes linked to disease into three categories: bone and skeleton, metabolism, and neurological and behavioural disorders.

One of the genes discovered, Elmod1, belongs to a large group of genes active in the brain for which there was no information about its function. This work revealed that mice with a faulty Elmod1 gene had lower blood glucose levels and lower body weight. It also revealed that this gene was involved in gait and the animals had a lower grip strength.

In order to study gene function, the EUMODIC consortium produced mouse lines which each had a single gene removed. These mouse lines were then analysed in mouse clinics, where each mouse was assessed by a series of tests and investigations, allowing the researchers to establish the functions of the missing genes.

EUMODIC was the first step towards the creation of a database of mouse gene functions, a vision now being realised by the International Mouse Phenotyping Consortium (IMPC).

The IMPC incorporates 18 centres from across the globe with the aim over the next ten years of uncovering the functions of all 20,000 genes in the mouse genome. IMPC builds on the groundwork and achievements of EUMODIC in establishing the procedures and processes to identify and catalogue the functions of genes.

Professor Steve Brown, Director of the MRC Mammalian Genetics Unit at Harwell and the coordinator of the EUMODIC consortium, said: “EUMODIC leaves a powerful legacy that will live on in the IMPC and the data and resources it has provided for scientists. EUMODIC and IMPC will be truly transformative for medical research by revealing the roles that different genes play in disease.” MRC UK

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Patients diagnosed with NSCLC have a poor prognosis, with a 5-year survival rate of only 16 percent. Researchers at Moffitt Cancer Center hope to improve NSCLC patient survival with the results of a study.

The researchers focused their attention on inherited genetic variations in genes called interleukins. They genotyped the DNA of 33 interleukin genes from 651 NSCLC patients.

“Interleukins have important roles in regulating cell growth, cell death and in the activation of the immune system,” explained Matthew Schabath, Ph.D., assistant member of the Cancer Epidemiology Program at Moffitt.  “Inherited genetic variations in interleukins and other genes can change their function and promote cancer development or control a patient’s response to therapy.”

The researchers discovered that patients who had certain genetic variations in interleukin genes had a better response to either surgery or chemotherapy, resulting in improvements in overall survival, disease-free survival and the amount of time until disease recurred.

This information could be used to personalise patient care in the future. “Discovery of biomarkers based on germline DNA variations represent a potentially valuable complementary strategy which could have translational implications for predicting patient outcomes and sub-classifying patients to tailored, patient-specific treatment,” said Schabath. Moffitt Cancer Center

While the overall rate of colorectal cancer (CRC) is declining, CRC specifically among young patients is increasing. Previous studies have shown that CRC in patients younger than 50 years old tends to be more aggressive than CRC in older patients. A University of Colorado Cancer Center study offers early evidence of genetic differences between CRC in young and old patients, possibly pointing toward different treatments and strategies in combating the young form of the disease.

“We saw differences in two important gene signalling pathways, PPAR and IGF1R, which are involved in regulating cell development, metabolism, and growth,” says Christopher Lieu, MD, investigator at the CU Cancer Center and assistant professor of medical oncology at the University of Colorado School of Medicine.

Alterations in these signalling pathways have been implicated in the development of several types of cancer.

The study compared the genetics of 5 colorectal cancer tumours from younger patients (median age 31) to 6 tumours from older patients (median age 73), sequencing 45 million “reads” from each tumour. The group then explored the data for significant differences between groups. In addition to the pathways PPAR and IGF1R, the study showed that younger CRC tumour samples were enriched for pathways responsible for metabolizing drugs.

“Chemotherapies challenge cancer cells and younger people may metabolize these chemotherapies differently than older patients. This may explain why our traditional chemotherapy treatments may be less effective for younger patients with metastatic colorectal cancer,” says Todd Pitts, MS, research instructor in the Developmental Therapeutics Program at the CU Cancer Center, and the study’s lead author. (Pitts notes that this hypothesis will require additional exploration.)

The group plans to validate the finding of these differences in a larger patient population. Then, if PPAR and/or IGF1R prove to in fact be important drivers of CRC in young patients, the group hopes to explore trials of drugs targeting these potential tumour drivers. Toward this goal, the group has gathered the important resource of tumour samples grown from the tissues of young CRC patients, allowing further preclinical genetic and drug testing. University of Colorado Cancer Centre