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30 March 2007The Central Office of Research Ethics Committees (COREC) has announced that it will be relaunched as the National Research Ethics Service (NRES) on 1 April 2007 (see press release). NRES will continue to be responsible for NHS research ethics committees (RECs) in England and to coordinate activities with their colleagues in Scotland, Wales and Northern Ireland.
The change reflects the decision to move from coordinating RECs to a research ethics review system. The new system comes in response to recommendations made by the Department of Health (DH) Report of the Ad Hoc Advisory Group on the Operation of NHS Research Ethics Committees in June 2005. This independent review was prompted by concerns that the REC system was, for example, bureaucratic, inefficient, and that decision making across RECs was inconsistent. In addition, changes were needed due to the introduction of the EU Clinical Trials Directive, which for the first time made ethic review and approval a requirement in law for clinical trials. Since DH report was published, the National Patient Safety Agency, of which COREC became a part in April 2005, has been consulting on the best way to make changes in the ethics review process.
NRES will now conduct a research ethics service, “…that will provide robust ethical review to protect the safety, dignity and well being of research participants as well as ensuring through the delivery of a professional service that it is also able to promote and facilitate ethical research within the NHS. The new service will feature a screening process conducted by Research Ethics Advisors to categorise applications as:
Advisors are expected to be able to fast-track applications the present no material ethical issues and provide advice to researchers early in the application process. The new service will also aim to improve the ethics review process by creating a Quality Assurance Programme that will build on the existing accreditation programme for RECs, more training for REC members and a means of capturing feedback from applicants.
22 March 2007California-based healthcare provider Kaiser Permanente hopes to enrol 500,000 of its 2 million adult members in northern California in an ambitious research programme (the Research Program on Genes, Environment and Health) that aims “to identify genetic and environmental factors that affect human health”. Volunteers will be asked to provide health and lifestyle information and, in some cases, samples for DNA extraction. Samples and information, coded to protect confidentiality, will be used for a range of genetic epidemiological studies to investigate associations between genetic variants, environmental/lifestyle factors and specific diseases. Pharmacogenetic studies will also be undertaken. The company says measures have been put in place to ensure the highest scientific and ethical standards for the research programme. Kaiser claims that its members are representative of the overall population, and that results from the research will provide benefits for the country as a whole. There is also provision for negotiation of access to the data by outside scientists. According to Science magazine, US National Human Genome Research Institute Director Francis Collins, who hopes to be able to set up a public sector population genomics resource, has welcomed Kaiser’s plans but points out that the insured population may under-represent some social and ethnic groups. Kaiser has secured seed funding of $7 million for its plans but substantial further funding will be needed.
20 March 2007Women who test positive in antenatal Down syndrome screening programmes and elect to undergo amniocentesis and diagnostic testing can experience great anxiety while they await the results of diagnostic karyotyping, which takes 2-4 weeks. A study for the UK’s Health Technology Assessment programme has found that maternal anxiety is reduced if women are given ‘early partial results’ from rapid molecular testing techniques during this waiting period. These molecular techniques, based on PCR or FISH analysis, can provide results in 3-4 days but are specific for the three most common trisomies (13, 18 and 21), whereas full karyotyping can also detect more rare chromosomal abnormalities.
When the molecular tests were originally developed there were suggestions that they might replace full karyotyping as the standard diagnostic method, because all but a very small percentage of the chromosomal abnormalities that they do not detect would be picked up in any case by routine ultrasound examination. It was also argued that because the usual indication for amniocentesis is a positive result from a Down syndrome screening test, most women undergoing amniocentesis are not at any higher risk of other abnormalities than screen-negative women, who are not offered diagnostic testing. However, others felt that because there is a risk associated with an invasive procedure such as amniocentesis, there is an ethical duty to obtain as much information from the sample as possible.
The issue has been debated over the last few years (see, for example, our newsletter story from July 2005). There is as yet no official national policy. A survey of 14 NHS cytogenetics laboratories carried out during 2006 found that 9 carried out both karyotyping and rapid diagnosis on all samples, one performed karyotyping only, and one performed only rapid diagnosis except where there were abnormal ultrasound findings. 2 laboratories carried out rapid diagnosis on samples for which the serum screening risk was particularly high (1 in 30 or 1 in 100).
The results of the new HTA study on maternal anxiety provide additional evidence to inform the debate about the best approach to antenatal diagnosis of Down syndrome and other chromosomal abnormalities.
16 March 2007The Home Office is currently advertising for a chair and up to 8 others to serve on the Ethics Group of the UK National DNA Database (NDNAD) (see advertisement). The Ethics Group will provide ethical review of NDNAD policy and decision making. The Home Office is seeking individuals with experience “at the highest level” in the areas of business, management, finance, public service, community work and the equalities field. The closing date for applications is 2 April 2007.
There have been calls for the NDNAD to institute some form of ethics review of its workings. In the 2002 Human Genetics Commission (HGC) report, Inside Information: Balancing Interests in the Use of Genetic Data, they recommended that “…the Home Office and Association of Chief Police Officers establish an independent body, which would include lay membership, to oversee the work of the National DNA Database custodian and the profile suppliers.” They also recommended that a separate national ethics committee be created to “…approve all research projects using human genetic information or material that can be linked to an identifiable person.” The House of Commons Science and Technology Committee, their 2005 report, Forensic Science on Trial, supported the HGC’s call for an ethics review committee. In response to these reports, members of the HGC were invited to sit on the NDNAD Strategy Board and it was agreed that an ethics committee would be established.
According to information provided by the Home Office, the role of the Ethics Group will be to:
Specifically, the Ethics Group will advise on applications for research that involve access to NDNAD samples or data; the operational services provided by suppliers that are dependent on access to NDNAD samples or data; and on other matters as they arise. No indication is given of when the Group is expected to begin its work.
12 March 2007A new society devoted to the implications of genetics for primary care practice has been launched in the UK. The Primary Care Genetics Society (PCGS) aims “to support and facilitate the educational needs of primary care practitioners to help translate the continuing advances in clinical genetics into practice”. Supported by the Genetic Interest Group and in partnership with Cancer BACUP and the UK Thalassaemia Society, the PCGS was launched at a conference in February on the relevance of clinical genetics to general practice medicine. Issues discussed at the meeting included family history and genetic screening, ethical issues facing primary care, management of chronic genetic conditions in primary care, and genetics in cardiovascular medicine and cancer. Presentations from the conference are available on the PCGS website, which aims to provide news and resources for primary care practitioners “dealing with an ever demanding public who are continually being fed information about genetics from various sources including the internet and the lay media”.
10 March 2007A study presented at a US Society of Gynecologic Oncologists (SGO) conference has reported that many American women at high risk of developing familial cancer syndromes such as familial breast-ovarian cancer and hereditary non-polyposis colorectal cancer (HNPCC) were unaware of their elevated risk, based on family history and genetic testing. Fewer still were said to discuss the implications of a diagnosis of familial cancer syndrome with their healthcare practitioners or genetic counsellors, or to access screening programmes or prophylactic interventions. Of over 2700 women attending mammography screening who completed questionnaires in the Californian study, more than 300 were reportedly found to be at high risk of a familial cancer syndrome - familial breast-ovarian cancer for the vast majority - but of these, fewer than 3% had undergone genetic counselling / testing at the time of the survey. Of note, the high incidence of women reportedly at high risk was no doubt influenced by the setting (a mammography centre); almost half of these high risk women had already had cancer themselves.
Commenting on the research report, SGO president Dr Andrew Berchuck said: "Although genetic testing for gynecologic and other hereditary cancers has been available for over a decade, awareness of this potentially life-saving intervention is woefully inadequate among both physicians and the public" (see press release). Improved awareness of and access to genetic services for high-risk patients is clearly an issue for parts of the US.
9 March 2007The Human Fertilisation and Embryology Authority (HFEA) has, after a public consultation exercise, decided to allow women to donate their eggs for research projects (see press statement). As this form of altruistic donation raises ethical issues, additional safeguards will be put into place to ensure that women are not being coerced into donating. These safeguards include giving the woman detailed information regarding the research being conducted, ensuring there is a separation between the people providing the treatment and the researchers, and making sure the person obtaining the consent from the women is independent of the research team. Women will not be paid for donating their eggs, as in other countries; they will only be paid for the expenses incurred during the donation process (up to £250). Also, women will be given a period of time during which she can reconsider her decision prior to her eggs being harvested.
The HFEA recognises that these safeguards are important as this issue has caused much debate (see news story). Some opponents argue that as human eggs are a scarce and precious resource, researchers should use alternative sources of eggs until their research methods are further perfected. Others worry about the potential for women to suffer side effects of their donation, such as ovarian hyperstimulation syndrome, when they are not receiving any benefits of the treatment in return. Proponents counter that women have been donating eggs for many years and should be allowed to make their own choices in this matter. The HFEA has agreed. As Angela McNab, Chief Executive of the HFEA, said in their press statement, “Given that the medical risks for donating for research are no higher than for treatment, we have concluded that it is not us to remove a woman’s choice of how her donated eggs should be used.” The HFEA do not expect a large number of women to begin donating as there are very few laboratories involved in this work. Earlier this year, the North East England Stem Cell Institute in Newcastle was awarded a temporary licence to approach women regarding altruistic donation (see news story).
30 March 2007The Framingham Heart Study, which began in 1948, is a well-known longitudinal study of risk factors for cardiovascular and other chronic diseases in a community based sample of people originally residing in Framingham Massachusetts in the United States. A new study on 1697 offspring enrolled in the study has revealed that those with the longest-lived parents (surviving to age 85 or older) have the most favourable risk profiles for cardiovascular disease (CVD) (Terry DF et al. (2007) Arch Int Med 167, 438-44). Compared to offspring with neither parent surviving to the age of 85, offspring with two long-lived parents had healthier scores for factors such as blood pressure, blood lipid levels, and smoking status. Those with one long-lived parent had intermediate CVD risk scores. The risk factor advantage of offspring with long-lived parents persisted over 12 years of follow-up. Perhaps surprisingly, no difference was found in body mass index (BMI) among the three groups. An intriguing finding in the study was the trend towards younger offspring ages in those with both parents surviving to age 85 or older. The authors suggest that “the ability to have children later in life may be a proxy for a delayed menopause and, perhaps, delayed ageing.”
Comment: This study confirms, in a community cohort, findings from previous studies that the children of long-lived parents also have a survival advantage, and a reduced prevalence of conditions such as heart disease, hypertension and diabetes. It is likely that genetic factors partly explain the reduced CVD risk of the offspring of long-lived parents. As the authors point out, the study cohort was predominantly white and middle class, so the results may not be generalisable to other racial/ethnic or socioeconomic groups.
10 March 2007A new analysis of cancer genomes has revealed the presence of substantially more mutations than previously suspected. In a recently published paper in Nature, a Cancer Genome Project team led by researchers from the UK Wellcome Trust Sanger Institute sequenced the genomes from more than 200 different human cancer cells. Cancer is known to arise via the accumulation of certain types of genetic mutation in dividing cells that together disrupt normal regulation of cellular function and growth, and lead to uncontrolled proliferation. These cancer-associated mutations are sometimes referred to as ‘driver’ mutations (for example, in genes involved in DNA proofreading and repair functions, or in cellular replication checkpoints); however, cancer cell genomes also include other mutations not specifically associated with carcinogenesis, dubbed ‘passenger’ mutations.
The Sanger team presents an analysis of more than 1000 mutations identified in the coding portions of over 500 protein kinase genes, a class frequently associated with cancer [Greenman C et al. (2007) Nature 446(7132):153-8] . They found that the majority of mutations were likely to be passenger mutations, but nevertheless identified potential driver mutations in more than 120 genes. Cancer Genome Project co-leader Dr Andy Futreal commented that "…buried amongst [passenger mutations] are much larger numbers of driver mutations than was previously anticipated. This suggests that many more genes contribute to cancer development than was thought" (see press release). The authors propose that the full repertoire of cancer mutations will not become apparent until thousands of cancer cell genomes have been systematically analysed.
Comment: This paper is an early publication from a very large cancer genome project, and reveals something of the range and complexity of cancer mutations that exist. As well as providing important new information about patterns of mutation in different forms of cancer and distinguishing features of passenger and driver mutations, it also identifies a wealth of novel cancer-associated driver mutations. These may prove extremely valuable in understanding the genetic and pathological processes that underlie cancer, and in the search for new drugs and other therapeutic approaches to combat the disease.19 March 2007What genome-wide association studies can do for medicine. Christensen K, Murray JC (2007) N Engl J Med. 356(11):1094-7. Perspective article explaining the identification of genetic variants associated with moderate disease risk and the need for new approaches to collect sufficient samples to permit wider studies in future (PubMed).
Structural variation in the human genome. Lupski JR (2007) N Engl J Med. 356(11): 1169-71. Clinical implications of basic research summary on the known and potential effects of copy number and other forms of structural variation (PubMed).
A future for medical genetics: lessons from Catch 22. Evans JP (2007) Genet Med. 9(1):1-3. Editorial on the necessity for medical geneticists to make clear the importance of their speciality – lest they become the only clinicians to sit out the genetic revolution (PubMed).
The case for dedicated sickle cell centres. Serjeant G (2007) BMJ 334(7591): 477. Personal view from the chairman of the Jamaica sickle cell trust.
Management of breast cancer in women with BRCA gene mutation. Kell MR, Burke JP (2007) BMJ 334(7591):437-8. Editorial on the safety of breast conserving surgery in women with familial breast cancer syndrome(PubMed).
Strategies for silencing human disease using RNA interference. Kim DH, Rossi JJ (2007) Nat Rev Genet. 8(3):173-84. Review on the potential and pitfalls of therapeutic RNAi based on recent findings (PubMed).
The evolution of epidemic influenza. Nelson MI, Holmes EC (2007) Nat Rev Genet. 8(3):196-205. Review on epidemiological evolution of human influenza virus proposing that a wider view of genomic diversity is required (PubMed).
The evolutionary significance of cis-regulatory mutations. Wray GA (2007) Nat Rev Genet. 8(3):206-16. Review of the relative contribution of coding sequence and cis-regulatory mutations to functionally significant change (PubMed).
100 years on: a century of genetics. Dunwell JM (2007) Nat Rev Genet. 8(3):231-5. Perspectives essay on the birth and enduring legacy of genetics (PubMed).
Beyond standardization: dynamic software infrastructures for systems biology. Swertz MA, Jansen RC (2007) Nat Rev Genet. 8(3):235-43. Opinion piece proposing key features for new software infrastructure to permit the high levels of complexity required by systems biology applications (PubMed).
HLA-DR15 Haplotype and Multiple Sclerosis: A HuGE Review. Schmidt H et al. (2007) Am J Epidemiol Feb 28; [Epub ahead of print]. Literature review and meta-anlysis of articles on the association between the DR15 haplotype and MS (PubMed).
Genetic contributions to Type 2 diabetes: recent insights. Sale MM, Rich SS (2007) Expert Rev Mol Diagn 7(2):207-17. Review of genetic factors associated with type 2 diabetes along with possible mechanisms of disease susceptibility and therapeutic opportunities (PubMed).
Genetics and epigenetics - nature's pen-and-pencil set. Gosden RG, Feinberg AP (2007) N Engl J Med. 356(7):731-3. Editorial accompanying research report on epigenetic transmission of disease due to uncorrected errors (PubMed).
A review of genetic causes of ischemic and hemorrhagic stroke. Tonk M, Haan J (2007) J Neurol Sci Feb 26; [Epub ahead of print]. Review on insights from rare monogenic forms of stroke that may be applied to the common, multifactorial forms (PubMed).
The Role of Genetics in the Provision of Essential Public Health Services. Wang G, Watts C (2007) Am J Public Health Feb 28; [Epub ahead of print]. Analysis of US state public health genetics programs and their impact (PubMed).
The effect of HapMap on cardiovascular research and clinical practice.
Skelding KA, Gerhard GS, Simari RD, Holmes DR Jr (2007). Nat Clin Pract Cardiovasc Med 2007 Mar;4(3):136-42. Review of the HapMap project and applications in cardiovascular research (PubMed).
Analysis of phenotype-genotype connection: the story of dissecting disease pathogenesis in genomic era in China, and beyond. Shen Y, Xu Q, Han Z, Liu H, Zhou GB (2007) Philos Trans R Soc Lond B Biol Sci Feb 27; [Epub ahead of print]. Discussion of how understanding the underlying genetic contributions to complex disease pathogenesis by genomic era research can lead to novel diagnostic and therapeutic strategies (PubMed).