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14 August 2000A brief article in the Journal of Medical Genetics summarises the findings of a survey on the current state of services for familial breast cancer in 34 European countries, including the members of the European and the countries of the former Soviet bloc, as well as Israel, Switzerland and Turkey [Hodgson, S.V. et al (2000) J Med Genet 37, 605-607]. As might be expected, the countries with the highest per capita wealth are the furthest advanced in developing and implementing cancer genetics services, as judged by factors such as the recognition of genetics as an offical medical specialty, the existence of training in cancer genetics, the setting up and maintenance of cancer registries, and the development of the roles of genetic nurses and associates. The full results of the survey are expected to be available soon on the website of the Journal of Medical Genetics.  

2 August 2000The Science and Technology Committee of the House of Lords has set up a 13-member Sub-Committee to inquire into human genetic databases. The aim is to finid out about existing databases, and about any sample collections from which genetic profiles might be obtained in the future. The Sub-Committee wants to know, for example, the purposes for which databases have been (or may be) assembled, what genetic information is being collected, how it is stored and its security safeguarded, and whether patenting issues are involved. It is also asking groups involved with genetic databases who is funding them, how they see the field developing in the future and whether there are lessons to be learned from similar initiatives in other countries. Groups with a current active interest in the field are asked to submit written evidence to the Sub-Committee by 4 October 2000. This evidence will be published and examined, together with further oral evidence, at meetings scheduled for November 2000 to February 2001. In March 2001 the Committee will report to the House of Lords; this report will include recommendations to both the Government and the Human Genetics Commission, which also has a remit in this area and has welcomed the Lords' inquiry. Those wishing to participate in the inquiry can obtain further information from the Clerk of the Sub-Committee, Roger Morgan, at morganr@parliament.uk  

21 August 2000Three subgroups of the Human Genetics Commission, considering genetic testing, public involvement in genetics and the storage, protection and use of genetic information, have published notes of their recent meetings on the HGC website. The Genetic Testing Subgroup discussed, among other issues, the draft report on Prenatal Genetic Testing, published earlier this year by the Advisory Committee on Genetic Testing. Although it was agreed to be important that the final version of the report should be published as soon as possible, to tie in with the forthcoming report of the NHS Working Group on Laboratory Services for Genetics and with the NHS guidance on commissioning specalised services, it was felt that the report as it stands does not reflect the fact that the HGC's remit is wider than that of the ACGT's, particularly in the area of the social and ethical implications of genetic testing. Changes were discussed that would express more clearly some of the disadvantages of prenatal genetic testing (including from the perspective of the child), add information on living with a disability, and stress that support must also be available to those who decline prenatal testing. A revised foreword to the report will explain that its remit is to improve practice in the commissioning of services for prenatal genetic testing, and that there is a need for further consideration of the social and ethical issues.

A joint meeting between the Subgroup on Public Involvement and the Working Group on the Storage, Protection and Use of Genetic Information discussed a plan to use the People's Panel to gauge public attitudes on the storage and use of genetic information and samples. This will involve 1000 face-to-face interviews, conducted by MORI, with the questions (the exact wording of which is very important) to be developed by a steering group from the HGC. The questions will cover "insurance, employment, genealogical and forensic uses of genetic information and the development of genetic databases and issues of consent, confidentiality and access to information". It is hoped to have the results from this initial sampling available in time to inform a wider consultation process during November 2000 to February 2001. Ideas for how to conduct this consultation were discussed by the Subgroup on Public Involvement, with an emphasis on the need for the HGC to find effective and possibly innovative ways of "taking the consultation to the people". These may include roadshows and use of the HGC website. The consultation process will be launched with a one-day public meeting in Newcastle on 27 November, which will include a tour of the city's Centre for Life together with a large group of local A-level and FE college students, and an evening open meeting that might perhaps be filmed.

The Working Group on Storage, Protection and Use of Genetic Information is drafting a consultation paper on this topic, for presentation to the full HGC meeting in September. Various difficult areas from this paper were discussed at the Group's meeting, including the definition of "genetic information" - does it include family history information, for example, or phenotypic characterstics resulting from a particular genotype? The Group felt that consent for a DNA test should be both "specific and informed" but decided that the issues were very different in relation to diagnostic testing compared with predictive/presymptomatic testing, and that additional questions also arise when considering samples that might be used in current or future research. In the area of confidentiality, the Group discussed the tension between the "right not to know" genetic information, and the problem that exercising this right could deprive other family members of information they may wish to have. The consultation paper will present both sides of the issue. The Group welcomed the prospect of working closely with the House of Lords Inquiry into Genetic Databases.   

8 August 2000The UK Huntington's Disease Consortium has reported the combined results, from all UK centres, of predictive testing for Huntington's Disease over the 10 years from 1987 to 1997 [Harper, P.S. et al (2000) J Med Genet 37, 567-571 (Abstract)]. Before 1993, testing had to be done indirectly using markers linked to the gene, and required samples to be taken from several family members. Since the identification of the Huntington's Disease gene in 1993, and the discovery that there is virtually no genetic heterogeneity, that is, all those with the disease have the same type of mutation in the same gene, testing has been both simpler and much more accurate. The Consortium reports that 2937 presymptomatic tests were carried out over the 10-year period, 85% of them based on direct analysis of the mutation. It is difficult to know exactly what percentage of people at risk of Huntington's Disease have taken up the offer of testing, but the Consortium estimates that about 18% of those at 50% prior risk (those with an affected parent) have done so. About 40% of tests results showed that the individual tested carried the Huntington's mutation. The analysis of testing over the 10 year period shows some interesting features, including a significant excess of women among those who elect to be tested (almost 60% were women) and a surprisingly high percentage of mutation-positive results (almost 30%) among people over 60 years old, indicating that the age of onset of the disease can be very variable. The Consortium suggests that experience with predictive testing for Huntington's will prove useful as testing becomes possible for more late-onset neurodegenerative diseases.

Comment: The results of this survey confirm the general experience that uptake of genetic testing for late-onset conditions, particularly untreatable ones, is quite low. The protocol for predictive testing for Huntington's, which includes extensive counselling, provides a good model for predictive testing for other rare, late-onset single-gene diseases. It is less easy to extrapolate to a possible future where testing may be available for predisposition to more-common late-onset diseases, where results will almost always be much less clear-cut. Here, the Huntington's counselling protocol may be less useful as a model: on the one hand, such rigorous psychological counselling might not be necessary when the result is likely to be much less dreadful, but on the other hand the complexity of the underlying genetics of common disease and the strong role of environmental factors mean that most people will need careful explanation of exactly what the result means for them.

16 August 2000The long-awaited report by the CMO's Expert Group on stem cell research and cell nuclear replacement has now been published. The report, entitled Stem cell research: medical progress with responsibility, recommends that research using human embryos with the aim of increasing understanding of human disease and deriving new treatments should be permitted, subject to the controls in the 1990 Human Fertilisation and Embryology Act. This recommendation applies to embryos created either by in vitro fertilisation or by cell nuclear replacement (where the nucleus of a donor cell is inserted into an egg that has had its nucleus removed). It would continue to be a criminal offence, however, to implant an embryo derived from cell nuclear replacement into the uterus of a woman - in other words, the current ban on "reproductive cloning" would be maintained. The Human Fertilisation and Embryology Authority would be responsible for assessing on a case by case basis all applications for research using human embryos. The Expert Group also recommends that the progress of research on the potential of stem cells derived from embryos should be monitored "by an appropriate body", and that if new treatments are developed from this research then the need for new legislation to allow these treatments to be used should be kept under review. Commenting on one specific potential use of cell nuclear replacement, the Group recommends that research should be allowed to proceed to investigate the possibility of using this approach to enable a woman carrying a disease-causing mutation in her mitochondrial DNA to have a healthy child. In its response, published at the same time as the Expert Group's report, the Government accepts the Group's recommendations in full and announces its intention to bring forward in parliament the legislation necessary to extend the research purposes for which human embryos may be used. It will allow a free vote on this legislation, which it accepts is controversial. At the same time it will strengthen legislation banning reproductive cloning, and bring forward legislation banning the production of "hybrid" embryos made from human nuclei and the eggs of any other species. 

9 August 2000The US company DNA Sciences Inc, one of whose directors is Nobel prize winner James Watson, is calling for thousands of people to sign up for their "Gene Trust" project, which aims to attempt to link DNA variations with susceptibility to specific diseases. The first diseases to be focused on are coronary heart disease, asthma, breast cancer, multiple sclerosis and type II diabetes. Volunteers are asked to register, and to fill in a confidential general health survey that may be followed by a detailed medical survey. Those whose profile matches one of those the company is looking for will then be asked to sign a formal consent document and provide a blood sample for DNA extraction. The company is aiming to enrol at least 5000 people with profiles of interest, but will need to screen the health profiles of hundreds of thousands in order to reach this target. Participants may withdraw their consent at any stage and will be contacted after three years to check that they still wish to be part of the project. DNA Sciences is not offering to pay the volunteers for their participation, but says that if the study a volunteer participates in leads to development of a new diagnostic test, the test will be made available free of charge those who participated. An "FAQ" web page about the Gene Trust sets out the company's plans for preserving the privacy of participants and the confidentiality of any information about their health or their genetic make-up. The aims of the project are very similar to those of deCODE, the company setting up a genetic database for the Icelandic population, and of the proposed Population Biomedical Collection in the UK. It will be interesting to see whether levels of altruism among the US population are high enough - and levels of suspicion low enough - for DNA Sciences to reach its target. Some are already asking why people should provide, for free, information from which the company expects eventually to make a profit. There is also disquiet at the lack of involvement of any independent third party to oversee the company's arrangements for preserving privacy and confidentiality. 

11 August 2000In an account of the highlights of its fifth meeting, held in public session on 5-7 June 2000, the Secretary's Advisory Committee on Genetic Testing reports on its progress in reviewing public responses to its draft recommendations on the oversight of genetic tests, and in amending its recommendations in the light of these submissions. The Committee decided to clarify the definition of a genetic test, which now includes tests on human DNA, RNA, genes and/or chromosomes, and in addition "the analysis of human proteins and certain metabolites which are predominantly used to detect heritable or acquired genotypes, mutations or phenotypes". The definition excludes other sorts of tests that may contribute to diagnosing a genetic disease but which are not primarily used for that purpose. In other changes to the draft recommendations, the Committee strengthened its recommendations on counselling and informed consent for genetic testing, and clarified the role it proposes for the Federal Drug Administration in the review of new genetic tests. Tests with different "levels of scrutiny" will require different levels of review. The Advisory Committee has also embarked on three new areas of investigation: genetics education and training of health professionals, informed consent of family members in genetics research, and the patenting of genetic tests, hearing expert presentations on these topics. 

3 August 2000Several recent papers discuss aspects of colorectal cancer screening. In the New England Journal of Medicine, Lieberman et al report a large study on over 3000 asymptomatic people aged 50-75 years, which showed that full colonoscopy detects many advanced tumours that are not detected by flexible sigmoidoscopy [Lieberman, D.A. et al (2000 N Engl J Med 343, 162-168 (Abstract)]. Similarly, Imperiale et al report that 50 people out of a total of about 2000 people screened by colonoscopy had cancerous lesions undetectable by sigmoidoscopy [Imperiale, T.F. et al (2000 N Engl J Med 343, 169-174 (Abstract)]. Commenting in the same issue of the journal, Podolsky argues, from an American perspective, that it is time to grasp the nettle and screen all average-risk people over 50 by full colonoscopy every 5-10 years [Podolsky, D.K. (2000 N Engl J Med 343, 207-208]. In his view, the arguments are overwhelming that screening would reduce mortality, and that other methods such as sigmoidoscopy simply miss too many tumours. He contends that in experienced hands the rate of complications in colonoscopy is less than 0.2%. Another type of screening, stool screening, is discussed in the BMJ, by Ahlquist [Ahlquist, D.A. (2000) BMJ 321, 254-255]. Fecal occult blood screening is already being piloted in the UK, but the problem with this method is that, compared with endoscopy, it may miss a significant percentage of tumours, and it carries a false-positive rate of about 5%. New stool screening methods based on the detection of cancer-cell DNA may eventually overcome these problems. The development of these methods is only just beginning, but it seems clear that it would be necessary to use a test that detected a panel of the most common mutations observed in colorectal tumours.

Comment: The paper by Podolsky illustrates an important difference between the UK and the USA in attitude to population screening. In the USA the term means, essentially, screening of those who can afford it, or have health insurance plans that will cover it. This certainly does not mean the whole of the population. In the UK, the NHS has to deliver any screening programme to all those in the population who are eligible. If the numbers are large (as they would be in the case of colorectal cancer screening) the pressure on the health service would be enormous and it is unlikely that the quality of colonoscopy could be maintained at as high a level as Podolsky assumes. For this reason, and because of cost considerations, regional cancer genetics strategies in the UK at present are concentrating on offering colonoscopy only to the much smaller numbers of people who are at genetically higher risk of the disease. Should fecal occult blood screening be rolled out on a national level, the numbers of those offered colonoscopy would inevitably increase dramatically, again leading to problems with costs, training and quality. Eventually, the development of a much better stool screening method, such as that outlined by Ahlquist, may be the best hope for the NHS if public pressure for universal colorectal cancer screening becomes irresistible.  

23 August 2000In a further report from the TRACE project (Trial of Genetic Assessment in Breast Cancer), mentioned in the March newsletter, Brain et al report the results of a prospective randomised trial in which 740 women with a family history of breast cancer were referred either for specialised genetic assessment and counselling, or to a breast clinic [Brain, K. et al. (2000) J Natl Cancer Inst 92, 1345-1351 (Abstract)]. Although the women who received specialised genetic assessment scored better on tests to determine their understanding of the genetics of breast cancer, the groups did not differ in various psychological outcomes such as satisfaction with the consultation and reduction of anxiety. The cost of specialised genetic assessment in this service model was estimated at £14.27 more than referral to the breast clinic, and the additional costs of testing and counselling in affected relatives brought the total increase to £60.98 per subject in the trial.

Comment: Brain et al question whether universal specialist genetic assessment for women with a family history of breast cancer is worthwhile in the light of their findings. Their study only measured certain psychological outcomes, however, and although they mention the additional costs of "cascade" counselling and testing of affected relatives of  high-risk women, they do not attempt to put any value (positive or negative) on this aspect of the service. This may merit further consideration. Brain et al also make the point that there may be subsets of women who will benefit substantially from specialist genetic assessment and counselling but further work will be needed to determine whether such groups can be identified.