Non-invasive prenatal testing (NIPT) for chromosomal foetal disorders is used increasingly to test for conditions such as Down’s syndrome. NIPT examines DNA from the foetus in the mother’s blood, and therefore does not carry the risk of miscarriage involved in invasive testing methods. Now, for the first time, researchers have found another advantage of NIPT; it can detect maternal cancers at an early stage, before symptoms appear.

Nathalie Brison, PhD, a senior scientist in the Clinical Cytogenetics laboratory at the Centre for Human Genetics, UZ Leuven, Leuven, Belgium, reports that the team had set out to increase the accuracy of the NIPT test in order to overcome some of the technical problems that can cause it to come up with false negative or false positive results when screening for chromosomal disorders in the foetus. Down’s, or trisomy 21, is the most frequent chromosomal abnormality, and occurs in about one in 700 live-born babies. The risk of giving birth to a baby with Down’s increases with the age of the mother, and rises sharply from the age of 36 years.

“We therefore felt it important that we improved the accuracy of the test,” Dr Brison says.  ”Even though it is very reliable, we believed that we could make it even better, and in doing so we could also find other chromosomal abnormalities apart from the traditional trisomy syndromes – Down’s, Edward’s (trisomy 18), and Patau (trisomy 13). Using the new, adapted test in over 6000 pregnancies, and looking at other chromosomes, we identified  three different genomic abnormalities in three women that could not be linked to either the maternal or foetal genomic profile. We realised that the abnormalities bore a resemblance to those found in cancer, and referred the women to the oncology unit.”

Further examination, including whole body MRI scanning and pathological and genetic investigations, revealed the presence of three different early stage cancers in the women:  an ovarian carcinoma, a follicular lymphoma, and Hodgkin’s lymphoma. Although this incidence is within the range to be expected in the normal population (one per 1000-2000 person years in women aged 20 – 40), without NIPT these cancers would have been unlikely to have been detected until they became symptomatic, and therefore at a much later stage.

“Considering the bad prognosis of some cancers when detected later, and given that we know that it is both possible and safe to treat the disease during pregnancy, this is an important added advantage of NIPT,” comments principal investigator Professor Joris Vermeesch, Head of the Laboratory for Cytogenetics and Genome Research at Leuven. “During pregnancy, cancer-related symptoms may well be masked; fatigue, nausea, abdominal pain, and vaginal blood loss are easily interpretable as a normal part of being pregnant. NIPT offers an opportunity for the accurate screening of high risk women for cancer, allowing us to overcome the challenge of early diagnosis in pregnant women.”

The results suggest that NIPT might enable the detection of pre-symptomatic cancers not just in pregnant women, but more widely. “We now know that it is possible to offer the accurate detection of chromosomally imbalanced cancers to the general population via minimally invasive screening methods,” says Dr Brison. “The normalisation of the NIPT profile in these patients following treatment indicates that we can also measure response to treatment as early as after the first administration of chemotherapy.  Of course, larger scale studies will be required to validate these results further, but we are confident that we have made an important step towards the possibility of wide-scale, effective, non-invasive cancer screening capable of detecting disease at an early stage.” European Society of Human Genetics

A new vaccine against HPV infections has the potential to prevent 90 per cent of all of the conditions triggered by the human papillomavirus. These are the findings of a randomized, controlled, international study involving a new, 9-component vaccine against HPV used on more than 14,000 young women aged between 16 and 26 years. The study was led by Elmar Joura from the University Department of Gynecology at the MedUni Vienna. The study has now been published in the “New England Journal of Medicine”.

Nine sub-types of the human papillomavirus are responsible for 85 per cent of pre-cancerous cells of the cervix. The new, highly effective vaccine now means that these can largely be prevented. The new vaccine is 20 per cent more effective against cervical cancer than the previous 4-component vaccine, up to 30 per cent more effective against the early stages of cervical cancer and up to five to 15 per cent more effective against other types of cancer (such as vaginal or anal carcinoma).

Human papillomaviruses (HPV) infect epithelial cells in the skin and mucosal tissue and can cause tumour-like growth. Some of these viruses also develop malignant tumours, especially cervical cancer in women. Men too can develop cancer caused by HPV infections, however. Over a hundred HPV sub-types have now been identified.

In Austria, up to 400 women a year develop invasive cervical cancer. In more than 90 per cent of the cases human papillomaviruses are responsible. According to Statistik Austria, around 150 to 180 women die from the condition. In Austria, around 6,000 women are admitted to hospital every year for treatment of the early stages of cervical cancer.
The paper has also been featured in the New England Journal of Medicine’s editorial, which is a major honour. “This issue of the journal reports on a milestone in research into cancers associated with the human papillomavirus (HPV)”, it says.

There has been a quadruple HPV vaccine since 2006 which protects against the most dangerous oncogenic HPV strains that cause cervical cancer and other types of cancer in the genital and throat area, but which also cause genital warts. The MedUni Vienna takes its responsibility in this area very seriously, and has not only initiated an HPV action day but has also provided a reasonably priced vaccination campaign for employees and students.

A 9-Valent HPV Vaccine against Infection and Intraepithelial Neoplasia in Women. E. A. Joura, A. Giuliano, et al. N Engl J Med 2015;372:711-23.

Medical University of Viennahttp://tinyurl.com/nb3n4xu

New research by an international team including Keck Medicine of USC scientists is bringing the origins of ovarian cancer into sharper focus.

The study highlights the discovery of three genetic variants associated with mucinous ovarian carcinomas (MOCs), offering the first evidence of genetic susceptibility in this type of ovarian cancer. The research also suggests a link between common pathways of development between MOCs and colorectal cancer and for the first time identifies a gene called HOXD9, which turns genes on and off, and provides clues about the development of MOCs.

‘It remains a mystery where these cancers come from,’ said Simon Gayther, Ph.D., professor in preventive medicine, Keck School of Medicine of USC, corresponding author of the international genome-wide association study (GWAS). ‘By finding these genetic markers, we begin to understand more about the biology of the disease itself. This study tells us more about the biology of ovarian cancer from the early development stage than most research has.’

Ovarian cancer is the fourth leading cause of cancer in American women and seventh most common cancer in women throughout the world (World Health Organization). In 2015, more than 14,000 American women will die of ovarian cancer, according to the American Cancer Society.

Most ovarian cancers have low survival rates, typically because of the misunderstanding of symptoms and discovery of the cancer in later, less treatable stages. ‘Although MOCs are a less common type of ovarian cancer with generally good prognosis when diagnosed in early stages, they are twice as likely to be resistant to treatment at later stages,’ said Andrew Berchuck, M.D., director of gynecologic oncology at Duke University Cancer Institute, and senior author of the study. ‘Our results will contribute to the identification of women at greatest risk of developing the disease with the long-term goal of prevention.’

The association analysis was based on 1,644 women diagnosed with MOC and more than 21,000 women without ovarian cancer. The research was conducted as part of the Collaborative Oncological Gene-environment Study (COGS), launched in 2009 with the goal of determining risks of breast, ovarian and prostate cancer. EurekAlert

What began as a chat between husband and wife has evolved into an intriguing scientific discovery. The results show a ‘highly significant’ correlation between periodic solar storms and incidences of rheumatoid arthritis (RA) and giant cell arteritis (GCA), two potentially debilitating autoimmune diseases. The findings by a rare collaboration of physicists and medical researchers suggest a relationship between the solar outbursts and the incidence of these diseases that could lead to preventive measures if a causal link can be established.

RA and GCA are autoimmune conditions in which the body mistakenly attacks its own organs and tissues. RA inflames and swells joints and can cause crippling damage if left untreated. In GCA, the autoimmune disease results in inflammation of the wall of arteries, leading to headaches, jaw pain, vision problems and even blindness in severe cases.

Inspiring this study were conversations between Simon Wing, a Johns Hopkins University physicist and first author of the paper, and his wife, Lisa Rider, deputy unit chief of the Environmental Autoimmunity Group at the National Institute of Environmental Health Sciences in the National Institutes of Health, and a coauthor. Rider spotted data from the Mayo Clinic in Rochester, Minnesota, showing that cases of RA and GCA followed close to 10-year cycles. ‘That got me curious,’ Wing recalled. ‘Only a few things in nature have a periodicity of about 10-11 years and the solar cycle is one of them.’

Wing teamed with physicist Jay Johnson of the U.S. Department of Energy’s Princeton Plasma Physics Laboratory, a long-time collaborator, to investigate further. When the physicists tracked the incidence of RA and GCA cases compiled by Mayo Clinic researchers, the results suggested ‘more than a coincidental connection,’ said Eric Matteson, chair of the division of rheumatology at the Mayo Clinic, and a coauthor. This work drew upon previous space physics research supported by the DOE Office of Science.

The findings found increased incidents of RA and GCA to be in periodic concert with the cycle of magnetic activity of the sun. During the solar cycle, dramatic changes that can affect space weather near Earth take place in the sun. At the solar maximum, for example, an increased number of outbursts called coronal mass ejections hurl millions of tons of magnetic and electrically charged plasma gas against the Earth’s magnetosphere, the magnetic field that surrounds the planet. This contact whips up geomagnetic disturbances that can disrupt cell phone service, damage satellites and knock out power grids. More importantly, during the declining phase of the solar maximum high-speed streams develop in the solar wind that is made up of plasma that flows from the sun. These streams continuously buffet Earth’s magnetosphere, producing enhanced geomagnetic activity at high Earth latitudes.

The research, which tracked correlations of the diseases with both geomagnetic activity and extreme ultraviolet (EUV) solar radiation, focused on cases recorded in Olmsted County, Minnesota, the home of the Mayo Clinic, over more than five decades. The physicists compared the data with indices of EUV radiation for the years 1950 through 2007 and indices of geomagnetic activity from 1966 through 2007. Included were all 207 cases of GCA and all 1,179 cases of RA occurring in Olmsted County during the periods and collected in a long-term study led by Sherine Gabriel, then of the Mayo Clinic and now dean of the Rutgers Robert Wood Johnson Medical School.

Correlations proved to be strongest between the diseases and geomagnetic activity. GCA incidence — defined as the number of new cases per capita per year in the county — regularly peaked within one year of the most intense geomagnetic activity, while RA incidence fell to a minimum within one year of the least intense activity. Correlations with the EUV indices were seen to be less robust and showed a significantly longer response time.

The findings were consistent with previous studies of the geographic distribution of RA cases in the United States. Such research found a greater incidence of the disease in sections of the country that are more likely to be affected by geomagnetic activity. For example, the heaviest incidence lay along geographic latitudes on the East Coast that were below those on the West Coast. This asymmetry may reflect the fact that high geomagnetic latitudes — areas most subject to geomagnetic activity — swing lower on the East Coast than on the opposite side of the country. While Washington, D.C., lies just 1 degree farther north than San Francisco geographically, for example, the U.S. capital is 7 degrees farther north in terms of geomagnetic latitude.

Although the authors make no claim to a causal explanation for their findings, they identify five characteristics of the disease occurrence that are not obviously explained by any of the currently leading hypotheses. These include the east-west asymmetries of the RA and GCA outbreaks and the periodicities of the incidences in concert with the solar cycle. Among the possible causal pathways the authors consider are reduced production of the hormone melatonin, an anti-inflammatory mediator with immune-enhancing effects, and increased formation of free radicals in susceptible individuals. A study of 142 electrical power workers found that excretion of melatonin — a proxy used to estimate production of the hormone — was reduced by 21 percent on days with increased geomagnetic activity.

Confirming a causal link between outbreaks of RA and GCA and geomagnetic activity would be an important step towards developing strategies for mitigating the impact of the activity on susceptible individuals. These strategies could include relocating to lower latitudes and developing methods to counteract direct causal agents that may be controlled by geomagnetic activity. For now, say the authors, their findings warrant further investigations covering longer time periods, additional locations and other autoimmune diseases. Princeton Plasma Physics Laboratory

Scientists at King’s College London have identified a single blood protein that may indicate the development of Mild Cognitive Impairment (MCI) years before symptoms appear, a disorder that has been associated with an increased risk of Alzheimer’s disease or other dementias.

The new research used data from over 100 sets of identical twins from TwinsUK, the biggest adult twin cohort in the UK. The use of twins in the study indicated that the association between the blood protein and a ten year decline in cognitive ability was independent of age and genetics, both of which are already known to affect the risk of developing Alzheimer’s disease, the most common form of dementia.

The study, the largest of its kind, measured over 1,000 proteins in the blood of over 200 healthy individuals, using a laboratory test called a SOMAscan, a protein biomarker discovery tool which allows a high volume of proteins to be measured simultaneously. Using a computerised test, the researchers then assessed each individual’s cognitive ability, and compared the results with the measured level of each protein in the blood.
For the first time, they found that the blood level of a protein called MAPKAPK5 was, on average, lower in individuals whose cognitive ability declined over a ten year period.

There are currently no treatments available proven to prevent Alzheimer’s disease, and prevention trials for Alzheimer’s disease can be problematic because to be effective, they must involve individuals at risk of the disease, who can be hard to identify. Studies using Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) brain scans have been shown to display visible signs of the disease before the onset of symptoms, but these types of scans are both timely and costly.

To date, few other studies have looked at the blood of individuals with very early stages of cognitive decline and therefore most appropriate for a prevention study. Identifying blood markers such as MAPKAPK5, which may indicate a person’s future risk of Alzheimer’s disease, could contribute towards the better design of prevention trials. King’s College London