Sep 18, 2008 Genetic test for breast cancer risk factor - By Rebecca Robey

A new, simple genetic test could improve the way breast cancer screening is approached in the UK, according to leading Cancer Research UK scientists. In a report published in the New England Journal of Medicine, the Cambridge University-based research team identified seven new gene variants that are associated with an increased risk of developing breast cancer. They found that by examining which of these variants a woman carries, they could classify the likelihood that she will develop breast cancer as being low, moderate or high. They suggest that this could affect the age at which a woman is encouraged to start having mammograms, and how frequently she subsequently has them.

Breast cancer is the second most common cancer in the UK affecting both men and women, and the risk of developing it is known to be partly influenced by an individual's genetic makeup. Two well-known but rare gene variants in the genes BRCA-1 and BRCA-2 carry with them between a 36 and 85 per cent chance of developing breast cancer. Screening for these gene variants is currently offered to women with a strong family history of breast cancer. In the new study, the researchers pinpointed seven additional gene variants that are also associated with an increased susceptibility to breast cancer. Importantly, they found that although each of these gene variants individually carries only a mildly increased risk of developing breast cancer, having two or more of these gene variants in combination carries a much greater increased risk.

Currently, NHS mammograms are offered to all women over 50. The researchers propose that testing women for these genetic variants would enable a more targeted approach to breast cancer screening. Dr Paul Pharoah, a member of the Cambridge team explained: 'We believe genetic testing has the potential to enable doctors to identify a woman at an increased risk of breast cancer who would benefit from mammography at an early age... and would also identify a 55-year-old woman with a low chance of breast cancer who possibly wouldn't need such regular checks'.

The genetic test would involve just a simple mouth swab and the technology required is already available. However, the proposal was met with some caution. The researchers estimate that these seven gene variants account for only a third of the genes that influence the risk of developing breast cancer, so the test could not be considered to be comprehensive. Dr Sarah Cant of Breakthrough Breast Cancer commented that the study 'raises interesting questions about how information on risk could be used to help decide who is eligible for screening', adding: 'However, breast cancer risk is affected by lifestyle and environment as well as genetics. These also need to be taken into account when determining risk'.

Sep 19, 2008 A growing demand for PGD for cancer predisposition

Inherited cancer predisposition is rare, however preimplantation genetic diagnosis (PGD) for this group of disorders is steadily increasing. Unlike other common indications for PGD such as cystic fibrosis, PGD for cancer predisposition avoids the inheritance of a very high susceptibility to developing cancer rather than inheritance of the disease itself.

Most cancers arise due to sporadic events (mainly environmental risks) and few individuals have more than one primary tumour in their lifetime. However, individuals with an inherited susceptibility are prone to developing more than one cancer in multiple organs, a risk that remains throughout their lives. In spite of clinical surveillance, surgery and other treatments, morbidity and mortality due the inherited mutation can be high.

For example, patients with inherited mutations in the APC gene can develop cancers of the colon, small intestine, thyroid, skin and brain. Therefore, even after prophylactic removal of the large bowel these patients require life long clinical surveillance for the detection of cancers in other parts of the body. One of the primary causes of death in individuals with inherited APC mutations following colorectal surgery is the occurrence of benign tumours known as desmoids because the anatomical location of these tumours can make surgical removal difficult.

The age of onset for inherited cancer is generally much earlier than in sporadic cases, but the penetrance of these disorders can be variable as not all individuals with an inherited mutation in a cancer predisposing gene develop cancer. Mutations in the APC gene result in an almost 100 per cent risk of developing colorectal cancer if prophylactic surgery is not carried out, however inherited BRCA1 mutations confer a 60-65 per cent risk of breast cancer in women.

By following up families with inherited cancer, better knowledge of the spectrum of tumours and the clinical complications that can arise has led to the creation of a number of guidelines for the clinical management of these patients. Once the causative germline mutation is identified in a family member with inherited cancer, other family members need genetic counselling to prepare for the stress of genetic testing. Even if cancer treatment is not required, asymptomatic mutation carriers undergo regular and often invasive clinical screening as well as prophylactic surgery in some cases. It is surprising that in spite of almost all types of inherited cancer showing autosomal dominant inheritance (where 50 per cent of offspring will have high genetic susceptibility to developing cancer), counselling on reproduction is rarely included in guidelines on clinical management.

Reproductive decision making for cancer predisposition is complex. This is because the extent of clinical manifestation due to a germline mutation is largely unpredictable and in some cases the availability of clinical surveillance for the early detection of tumours results in a favourable prognosis following treatment. For some couples termination of an established pregnancy because of cancer susceptibility is inappropriate yet passing on this genetic burden equally is not an acceptable option. PGD gives individuals with known germline mutations an opportunity to avoid passing on the inherited cancer risk to their children without the need to consider the termination of pregnancies.

In PGD genetic testing is carried out on embryos from the couple created by IVF. Only embryos that do not carry the inherited mutation are transferred back to the mother with the aim of establishing a pregnancy. In practical terms, children born following PGD for cancer predisposition avoid the need to prepare for a genetic test, where a positive result would have a significant impact throughout their lives whether or not they were to ever develop cancer.

In our experience, couples requesting PGD for cancer predisposition want to remove the burden of having an inherited mutation in these genes even if they themselves have not had clinical screening or cancer treatment, for example male carriers of BRCA1 mutations. We have carried out a total of 11 cycles of PGD for eight couples with inherited mutations in four different cancer predisposing genes. Three of these couples have had the birth of a healthy child following PGD to avoid retinoblastoma, neurofibromatosis type 1 and familial adenomatous polyposis and two others have ongoing pregnancies (retinoblastoma and inherited breast/ovarian cancer due to BRCA1).

PGD is therefore a highly successful option for couples with cancer predisposition as the live birth /pregnancy per cycle of PGD is 45.5 per cent (5/11) and per couple it is 62.5 per cent (5/8). The HFEA has licensed PGD for other cancer predispositions including von Hippel Lindau syndrome, multiple endocrine neoplasia type I and neurofibromatosis type 2. Worldwide, PGD has been carried out for inherited mutations in a number of different genes including MSH2, MLH1, RET, BRCA2, TSC2, and CDH1.(1) We are working towards developing PGD for inherited mutations in these genes so that more couples in the UK can be offered PGD as a reproductive option.

Sep 20, 2008 Major genetic cause of colorectal cancer identified - By Rachael Dobson

Scientists have identified one of the leading genetic causes of inherited colorectal cancer, reported in the journal Science. Research teams at the Northwestern University Feinberg School of Medicine and the Human Cancer Genetics Program at Ohio State University found that abnormal activity of the transforming growth factor-beta type 1 receptor (TGFBR1) gene is associated with a greater risk of developing colorectal cancer.

Approximately one third of colorectal cancer cases are believed to genetically inherited, though many of the genetic abnormalities have yet to be identified. 'This probably accounts for more colorectal cancers than all other gene mutations discovered thus far,' said Dr Boris Pasche of Northwestern University, who lead the study with Professor Albert de la Chapelle, Ohio State University.

The researchers compared the DNA of 242 colorectal cancer patients, and 195 healthy controls. In patients with colorectal cancer, 10-20 per cent had abnormal production of TGFRB1, compared to 1-3 per cent in the control group. This genetic abnormality was clustered in families and dominantly inherited. Patients with abnormal TGFRB1 production were nine times more likely to develop colorectal cancer than healthy controls, with an estimated overall lifetime risk of developing the cancer at fifty per cent.

'There is not a conventional mutation,' said Professor de la Chapelle. The team found that the increased risk of developing colorectal cancer was linked to differences in the activity of the TGFBR1 gene, known as Allele Specific Expression (ASE), rather than a mutation in the gene. Each person has two copies, or alleles, of every gene in their genome, one inherited from the father and the other from the mother. The researchers found that when one copy of the gene was less active, there was reduced production of TGFBR1.

TGF-beta is an important cell signaling molecule involved in inhibiting cell growth and has been linked to colorectal and other cancers. In this study the researchers have identified one major mechanism of action.

The researchers stressed that the results will need to be replicated in a larger study involving many more patients. They also noted that their findings may be different in other ethnic populations, for example in African or Asian groups. Non-genetic risk factors for colorectal cancer include a diet high in fat and calories, and low in fiber; obesity; a sedentary lifestyle; alcohol consumption and smoking.

The research group hopes to develop clinical tests to identify abnormal expression of the TGFRB1 gene in families with colorectal cancer history. 'We will be able to identify a larger number of individuals that are at risk of colorectal cancer and, in the long term, maybe decrease the cases of colorectal cancer and of people dying from it by being able to screen them more frequently,' said Dr Pasche.

Sep 21, 2008 Experts call for crackdown on sham genetic testing - By Ailsa Taylor

New standards of best practice will be drawn up in the UK to try and control the boom of unregulated genetic tests now being marketed to the public via the internet, says Christine Patch, Genetic Counsellor at Guys and St Thomas' Hospital and Human Genetics Commission (HGC) member. A consultation process involving individuals from industry, government, public bodies, charities and other stakeholder groups is already underway to try and flesh out the new guidelines and determine how best they should be implemented and policed, she told delegates of the British Society for Human Genetics annual conference today.

Patch said: 'The need for clear standards of practice is widely recognised and largely welcomed by industry and other stakeholder groups. What is not yet agreed is who should develop and oversee such guidelines and whether they should be written into European law or limited to the UK.'

Patch continued: 'When families access genetic testing through the NHS, they receive pre- and post- test counselling to make sure that they understanding the full implications of the test, both for themselves and other family members, and also the meaning of the results, which may subsequently inform important lifestyle or reproductive decisions. But when accessed without specialist medical support, such tests have the potential to be misinterpreted by the patient or even GP, causing unnecessary anxiety and potentially leading to mis-informed decision making.'

With so many unverified tests now on the market - claiming to assess an individual's risk of everything from breast cancer to ability to taste brussel sprouts - there is a real danger that the public may lose faith in genetic testing completely, believes Patch. 'If the promise of genomics to improve health is to be realised without causing harm or loss of public trust, developments in the evaluation and control of supply of tests may be as important as the science itself,' she said.

Over recent years, consumer's ability to obtain laboratory tests directly and without medical advice has been increasing, sparking concerns over the scientific validity of such tests and their potential to be misleading if interpreted by someone without specialist training. The HGC first recommended that there should be greater oversight of genetic testing in 2003, when only a few service providers were marketing tests direct to the public. But the recent surge in such tests means that the need for standards of best practice to protect public health is now very urgent, says Patch, who advises families at high risk of a genetic condition.

Sep 22, 2008 Genetic test reveals that Google co-founder has mutation linked to Parkinson's disease - By MacKenna Roberts

In addition to Google's corporate sponsorship of nearly 2 million pounds last year, Google co-founder Sergey Brin has taken his support of the genome-testing company 23andMe, which his wife co-founded, to new personal heights by becoming one of its customers. Last week Brin publicly posted on his blog that DNA testing of his saliva sample by 23andMe had detected that he possesses a genetic mutation which causes him to have what he explained is 'a markedly higher chance of developing Parkinson's disease in my lifetime than the average person', admitting that 'the exact implications of this are not entirely clear'. He wrote that his increased chances are 'somewhere between 20 per cent to 80 per cent depending on the study and how you measure'.

Among the results, a match was found on Brin's LRRK2 gene for the variant sequence G2019S, associated with an increased risk for Parkinson's. Parkinson's disease is a neuro-degenerative disorder of the central nervous system that often impairs speech and movement. Brin's mother and her aunt suffered from the condition but Brin said he was sceptical that it was genetic. When he agreed to have his DNA analysed by the California-based company, he had not intended to test for this condition.

However, Brin considers himself 'fortunate' to have learned 'early in his life' at 35 that he has this mutation so that he may take preventative steps 'to reduce his odds' of developing the disease, such as through exercise, which studies suggest may help. Brin added that he can now personally research and prepare himself and his family as well as use some of his Google fortune (an estimated $15.9 billion US) to help fund medical research into Parkinson's.

Brin's surprising move to disclose his personal DNA-testing result so publicly exemplifies his belief that genetic data should be shared as an open-source informational tool for everyone to mutually learn and benefit from discoveries of ways to improve their lifestyles in light of known genetic information. This comes at a time when the predominantly unregulated direct-to-consumer genetic testing industry has come under fire by authorities and scientists to crackdown with strict new regulation.

Online direct-to-consumer genomic scans like those offered by 23andMe are advertised as recreational or 'lifestyle' services that help you learn about your genetic identity. While some of the tests screen for non-medical characteristics, like the ability to smell asparagus in one's own urine, others like Brin's G2019S mutation can reveal personal information that bears serious medical diagnostic implications.

Experts warn that bogus tests may cause individuals needless anxiety or false complacency. Many serious medical conditions like heart disease are caused by a complex interplay of multiple environmental and multiple genetic factors. The predictive value of isolated genetic information must be placed within this context, and the implications for many genetic tests are not fully understood. Critics advocate legally requiring genetic counselling and limiting genetic testing by physician-referral only.

Although 23andMe has welcomed good-practice standards, it objected to physician involvement preventing a direct-consumer market. Brin and his wife Anne Wojcicki contend that DNA-analysis is not medical testing but a new source of important genetic information about one's identity that should not be restricted. They argue direct-to-consumer testing should be regulated like over-the-counter pregnancy tests.

In June 2008, the US passed a law that restricts the use of genetic information by employers and health insurers, but left the private genetic testing industry unregulated. The UK, US and Australia have issued national warnings regarding online testing and initiated government consultations for regulatory reform. New York and California health officials recently authored cease-and-desist letters to leading genomic companies, including 23andMe, demanding licensing compliance and doctor approval. Last month, California licensed 23andMe and Navigenics. The American Medical Association endorsed these state initiatives with new policies at its annual meeting this year.

Sep 23, 2008 More women delaying parenthood, Australian study suggests - By Ailsa Taylor

The average age of women seeking fertility help in Australia has increased from 35.2 years old in 2002 to 35.6 years old in 2006, according to a report by the Australian Institute of Health and Welfare (AIHW). The report showed that record numbers of women over 40 were undergoing fertility treatment - rising from 14.3 per cent in 2002 to 16.2 per cent in 2006 - despite those over 45 having only a two per cent chance of becoming pregnant.

The figures may echo a growing trend in the number of couples delaying parenthood, says Peter Illingworth, a Sydney- based doctor and president of the Fertility Society of Australia .'The vast majority of couples we see who are over 40, for example, have only just met', he told the Bloomberg Press. 'It's not that they have made a conscious decision to do it in their 40s, it's that the opportunity to have children has only just arisen later on in a woman's life', he added.

The report highlighted a 4.6 per cent increase in the number of couples undergoing Assisted Reproduction Techniques (ART), rising from 46,481 in 2002 to 48,706 in 2006. In total 10,522 babies were born in Australia and New Zealand as a result of ART in 2006, with numbers rising at an average rate of 5 per cent per year between 2002 and 2006. Of these, 78 per cent were singleton births, reflecting the recent drive to make single embryo transfer (SET) the policy of all fertility clinics.

Professor Michael Chapman, Head of Women's and Children's Health at the University of New South Wales in Sydney told The Age that fewer women than ever were having multiple births, with fewer than one per cent of women having more than two babies.

'The multiple pregnancy rate, which six or seven years ago was in the 20 per cent range, is now down to 11 per cent', he said, adding: 'It's virtually halved from its peak and that's good for the parents, it's good for society, because many of them end up in special care units and with long-term medical problems'.

The aim of SET policy is to avoid the risks associated with multiple births, such as premature birth, low birth weight, an increased risk of death in the first week and an increased risk of cerebral palsy around four times that for singleton births. However, SET is not always considered the best policy. For example, some experts have criticised the recent decision to make SET part of UK fertility guidelines, pointing to the low success rates of IVF, the lack of state provision on the National Health Service and the high private fees.

Sep 24, 2008 First pluripotent stem cell patent granted in Japan - By Benjamin Jones

The Japanese Patent Office has granted the first patent for induced pluripotent stem cells (iPS cells) to Kyoto University, where researcher Shinya Yamanaka produced both the first non-human iPS cells in 2006 and, using the same process, the first human iPS cells in 2007.The Japanese patent, a limited version of a much broader international patent application covering all forms of iPS cell (excluding germ cells) across all species, covers only human iPS cells created using Yamanaka's process based on reprogramming adult cells using four genetic factors.

The granting of the patent in Japan was fast-tracked by Patent Office officials so as to make clear the University's claim while the broader patent goes through lengthy processing across the world's other major patent institutions. The urgency in part reflects the contemporaneous progress of a US team headed by James Thomson at the University of Wisconsin which published its own successes in producing human iPS cells on the same day as Yamanaka in 2007.

The international patent applications, some of which are in Yamanaka's name solely (including the potentially lucrative US patent), may eventually cover a huge range of therapeutic applications and future avenues of research. Uncertainties have been raised, however, about whether the patent phrasing does enough to preclude others (such as Thomson's group who used a different set of genetic factors to create their iPS cells) from pursuing patents for their own distinct methods of preparation.

Hideya Hayashi of Kyoto University's iPS Cell Research and Application office is quoted in the journal Nature saying that the aim of the patent is not to restrict others from pursuing iPS technologies but instead to ensure that Yamanaka's group are not tied by other future patent applications. 'We want to remove any potential obstacles to the quick clinical application of IPS technology', Hayashi told Nature, adding that 'we are not trying to confine its use'.

The university has claimed it plans to grant licences and assistance in replicating Yamanaka's technology to institutions and non-profit organisations across Japan. The main concern, preventing a large pharmaceutical company from taking out a patent and then forcing universities to pay for the right to employ the technology, has been partially allayed by this first patent, which secures Yamanaka's basic process until 6 December 2026. However, it will be an anxious wait over the coming year while the rest of the international patents finish being scrutinised.

Sep 25, 2008 Hope for treating spinal injuries

Researchers have generated a specialised type of nerve cell - astrocytes - from embryonic stem (ES) cells. The astrocytes were used to treat spinal injury in rats, with impressive results, restoring their ability to move freely. The team of scientists from the University of Rochester, New York, and the University of Colorado, Denver, US, published the work last week in the online Journal of Biology.

The researchers developed a system to generate astrocytes from ES cells and found that two different types could be grown, by using different conditions to nurture the stem cells. Astrocytes are nerve cells that have a star-like shape, and account for 70 per cent of all cells in the central nervous system. They play numerous roles in maintaining the structure, metabolism and function of the brain and spinal cord.

When transplanted into spinal injury sites in rats, the two types of astrocyte had completely different effects. One promoted the regeneration of nerve cells, and limb movement was recovered within four weeks. The other type failed to promote nerve fibre regeneration or recovery of movement and, in addition, caused severe pain.

Controlling the development of stem cells immediately before transplanting them into injured spinal cords is essential. This is because the injured tissues of the body cannot be relied on to create the right types of cells from stem cells. This is illustrated by the fact that when the researchers implanted the stem cells (before they were astrocytes), they failed to promote nerve regeneration and caused pain. The researchers say this is a breakthrough that will change the way spinal cord injuries are treated with stem cells.

'It has long been a concern that therapies that promote growth of nerve fibres in the injured spinal cord would also cause sprouting in pain circuits', said Dr Stephen Davies, from the University of Denver. He added: 'However by using the right astrocytes to repair spinal cord injuries we can have all the gains without the pain, while these other cell types appear to provide the opposite - pain but no gain'.

The team is working on extending its research to human cells. Dr Davies told the Telegraph newspaper: 'We hope to translate this promising new cell replacement therapy to clinical trials within the next two to three years if all goes well'.

Sep 26, 2008 NHS suffers under the strain of multiple births resulting from 'fertility tourism' - By Sarah Guy

A report has indicated for the first time the cost faced by the UK's National Health Service (NHS) as it copes with multiple births resulting from IVF patients treated abroad. New research undertaken by the Fetal Medicine Unit at University College London Hospital (UCLH) makes a link between higher order multiple pregnancies (triplets and above) and the numbers of women travelling to other countries for fertility treatment.

The ten-year study carried out in London and revealed in Montreal last week at the Royal College of Obstetricians and Gynaecologists (RCOG) 7th International Scientific Meeting, showed that of the 94 women expecting three babies or more as a result of IVF treatment, 24 of them had received their treatment abroad. The women were treated in countries including Cyprus, Algeria, France, Germany, Belgium, the US, Greece, India and Japan and were reported to be 18 per cent less likely than their UK-treated equivalents to opt for embryo reduction.

The research highlights the potential dangers to women seeking IVF treatment abroad where there is less regulation of the numbers of embryos transferred into the womb; UK regulation recommends that in most cases only one embryo is implanted to reduce the instances of multiple births which are linked to dangerous and often life-threatening conditions for mother and baby.

Dr Alastair McKelvey, lead author of the study, believes that international agreement on this particular aspect of women's health needs to be agreed upon in order to reduce the 'huge cost burden' of increased ante- and neonatal care associated with multiple births. Recent research carried out by Sheffield University found that the extra care required by IVF twins and triplets cost the NHS £9,000 and £32,000 respectively. Dr McKelvey said: 'triplet, quadruplet and higher order multiple pregnancies are very challenging high-risk pregnancies. We were concerned, through personal experience, about the extent of this problem and its link to unregulated fertility care on the world market. National regulatory bodies can be sidestepped by couples desperate for a baby and ... fertility treatments can lead them to serious adverse consequences'.

British women and couples have many reasons for travelling abroad for IVF treatment. These include higher success rates due to transferral of more embryos, cheaper treatment, and availability of more 'ethnically acceptable' embryos. Women then return to the UK where the NHS provides care for their babies who often number more than two and are therefore more likely to be born prematurely.

Sep 27, 2008 Bone marrow stem cells used to treat strokes in mice - By Charlotte Maden

A group of US researchers have found that injecting human stem cells derived from bone marrow into the brain after it has suffered a stroke can alleviate symptoms. The research was carried out at the Center for Gene Therapy, Tulane University, New Orleans, and reported in Proceedings of the National Academy of Sciences.

Strokes are characterised by reduced blood flow to the brain caused by a blockage or bleed, thereby starving the brain of blood. An immune response ensues, during which healthy tissue is attacked and nerve damage is caused. Stroke is the third most common cause of death in the UK, and also the leading cause of severe disability. Every year 150,000 people in the UK suffer from a stroke - mostly people over 65 - but it can affect people of all ages.

During the study, a stroke-like state was simulated in six mice by blocking their carotid arteries and therefore halting the flow of blood to the brain. The researchers then injected the mice with human mesenchymal stromal cells (bone marrow stem cells), and found that neuron damage was reduced by up to 60 per cent.

Instead of generating new cells as expected, the team revealed that the cells exerted the effect by changes in gene expression, resulting in production of biochemicals which reduced inflammation. After the blood flow was stopped, 586 genes were more active in untreated mice. In mice injected with stem cells, 10 per cent fewer of these genes were more active. This suggests that those genes are likely to be involved in the immune response. In addition, the motor responses of the treated mice were dramatically improved, shown by better performances in movement, cognitive and behavioural tests than untreated mice.

Professor Darwin Prockop, co-author of the study, said that it 'provides for the first time a molecular explanation of how adult stem/progenitor cells can ameliorate ischaemic (reduced blood flow) damage to the brain'. He also highlighted that 'the fascinating thing was the cells were talking to each other - human cells and mouse cells' and that 'the human cells specifically turned down immune and inflammatory responses'.

The team is currently building a facility of sufficient standard to produce stem cells for use in patients, and is planning further testing of the technique in animals for efficacy and toxicity. Following this, human clinical trials should begin in the hope that stem cells can be used to treat strokes in humans in the future.

Sep 28, 2008 Low-cost hereditary breast cancer test could be available by next year - By Ailsa Taylor

By next year it could be possible to sequence the entire coding regions of BRCA1 and BRCA2 genes, which can put women at risk of developing hereditary breast cancer, for as little as £10, Professor Graham Taylor, Head of Genomic Services at Cancer Research UK, told delegates at the British Society for Human Genetics last Wednesday. 'Next generation' sequencing technology could slash current prices by up to 99% and is poised to deliver groundbreaking advances in genetic diagnosis across a whole spectrum of inherited conditions, says Professor Taylor, who is trialling the approach in collaboration with colleagues from Yorkshire and Wessex Regional Genetics Laboratories.

When the Human Genome was first sequenced in 2003, it was an expensive and labour-intensive process, taking some eight years to complete and costing the UK taxpayer in the region of £3 billion. But in the five years since, cheaper, easier and faster sequencing techniques have been developed, allowing much larger stretches of DNA to be sequenced at just a fraction of the cost.

Professor Taylor said: 'The emergence of next generation sequencing technologies has largely been spurred on by the field of genomics, where scientists have been trying to unravel the genetic basis of many common diseases, such as diabetes and cancer, by scanning the entire genomes of thousands of individuals at a time. What we've done is take this technology and see if it can be used to look for gene changes in a tiny fraction of the genome, for example a single gene.'

It is estimated that 5-10% of breast cancer patients have an inheritable form of breast cancer due to a mutation in one of two genes known as 'BRCA1' and 'BRCA2'. In their 'normal' state, these genes protect against cancer within the cell. However, women who carry a mutation in either of the genes have up to an 80% chance of developing breast cancer during their lifetimes. Currently, women can be tested for defective copies of the two genes, but this involves full genetic sequencing, which can take weeks and is very expensive.

Next generation sequencing technology allows several samples of DNA to be screened at a time, meaning that hundreds of diagnostic samples can be sequenced in one week, compared to the 18-week turnaround time associated with traditional methods.

Pilot studies are already underway to examine the potential for next generation sequencing technology to be used to diagnose a range of hereditary cancers, with results expected early next year.

Sep 29, 2008 Anti-depressants may be linked to male infertility - By Antony Blackburn-Starza

Anti-depressants may be linked to male infertility, say researchers at the Cornell Medical Center in New York. Results of a study reported in the New Scientist this week reveal that males taking anti-depressants - also known as selective serotonin reuptake inhibiters (SSRIs) - could be damaging their sperm. The study was performed by Peter Schlegel and Cigdem Tanrikut on 35 health male participants who were given paroxetine, which is marketed as Paxil or Seroxat by GlaxoSmithKline. After four weeks of taking the medication, it was found on average the proportion of sperm that became fragmented (damaged) nearly doubled, rising from 13.8 percent to 30.3 percent.

Sperm damage has been linked to male infertility and it is believed may also contribute to a decrease in embryo viability, although in itself the results do not mean males taking SSRIs will encounter fertility problems. In an abstract of the study made available to Reuters, the authors said: 'The fertility potential of a substantial proportion of men on paroxetine may be adversely affected by these changes in sperm DNA integrity.' In 2006, nearly two million prescriptions for peroxetine were issued.

Doctors have warned that the study should not prevent individuals with depression from seeking or stopping medical intervention. 'Patients shouldn't stop their antidepressants, but those who are depressed and experiencing fertility difficulties may wish to discuss this with their GP,' said Steve Field, chairman of the UK's Royal College of General Practitioners. Other experts have questioned the significance of the findings because, although they may seem alarming, the clinical significance may be low. Dr Allan Pacey, Senior Lecturer in Andrology at the University of Sheffield, said that further research is needed. 'It is a shame that the authors appear not to have conducted a randomised controlled trial which would be the most scientific way to investigate the drugs' effects, but I agree that the results are of concern and need to be investigated further,' he said.

Glaxo told Reuters that it was reviewing its own findings on the drugs, as the study was not mandated by the company. A Glaxo spokeswoman said: 'These medicines remain an important option, in addition to counselling and lifestyle changes, for treatment of depression and this study should not be used to cause unnecessary concern for patients.' Other medical experts have highlighted that risks are in inherent part of taking medication. '[Anti-depressants] are powerful drugs, so in a sense it is no surprise that research is discovering more about their impact on the body,' said Dr Andrew McCulloch, of the Mental Health Foundation.