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A practical guide to human cancer genetics
WOOK [~EVIEWS that AIDS is caused by a defect in antibody production. I was also rather distracted by the way in which individual articles are not always continued on consecutive pages, but are interspersed with other items. Although typographical errors are not numerous, they are apparent. All in all, Cancer Watch does an admirable job of achieving its goals of communicating cancer, cancer research
and cancer genetics. It is suitable for the uninitiated but informed lay person, and for the high-school student, college student and novice medical student. One aim of Cancer Watch is to 'cuhivate an appreciation for bioscience in highschool and college students', and perhaps encourage them to enter biomedical research. Perhaps more biographies of researchers, such as the one of Dr Nori, would bring a personal
Freak scene PlantGeneResearch:CellOrgandies editedby R.G.Herrmann Springer-Vedag, 1992. DM 229.00 hbk (vii + 467 pages) ISBN 3 211 82264 X For a long time I introduced lectures and seminars on chloroplast DNA by pointing out that it encoded the most abundant protein in the world (the large subunit of ribulose b/s-phosphate carboxylase, for the uninitiated). It shames me to admit that this was partly owing to some kind of paranoia that organelle DNA was seen by many as a mildly frivolous side-issue. So it comforted me to see that I wasn't the only one feeling this way, on reading in Reinhold Herrmann's preface to
Plant Gene Research: Cell O~anelles that 'Non-Mendelian inheritance was considered a research sideline - if not a I"reak - by most geneticists...' (While we're talking about sidelines, I might mention that, at least in the 17th and 18th centuries, 'freak' meant not only something unusual, but also, quite specific:ally, a variegated plant. So John Milton wrote in his poem Lycldas of '...the pansy freaked with jet...' Appropriate then, that the subject of organelle genetics should be referred to as freakish when the first insights into it came from the work of Baur and Correns on the inheritance of variegation in plants. But enough of my attempts at erudite footnotes.) The book sets out to give an 'up-todate account' of the subject, 'indicative of its growth, vitality and momentum', and I believe it succeeds. If I had to find a criticism, it would probably be with the title of Cell Organelles, since the book essentially limits itself to plastids and mitochondria, although there is one chapter on glyoxysomes and peroxisomes. The other organelles don't really get a look in. Within that restriction, the coverage is generally good, ranging from classical through to molecular genetics, from evolution to the control of gene expre~ion, and from algae (concentrating on Chlamydomonas) to Zea. Certainly, the book will be invaluable to anyone who, like me, gives
final-year undergraduate lectures on the molecular genetics of plastids and plant mitochondria (not to mention the undergraduate who has to sit through them). In fact, anyone working in this field of research should find this a useful and authoritative set of reviews, and I am happy to recommend it. Presentation of the volume is generally good, although the language of some authors is a little quirky. Diagrams are clear and typos are kept to a mininmm. My friends chide me for looking out for typos, but collecting them can be fun. Well it's got to be better than trainspotting, and I haven't got an anorak, anyway. I remember a book of conference abstracts where the name of a
touch and be an inspiration to students of science.
ChaffsEng CRCHuman CancerGeneticsResearchGl~up, Departmentof Pathology, Unitkorsi(t,of Cambridge, Cambridge, UKCB21QP,.and Division of Medical Oncolo~, Dana-Father CancerInstitute, Departmentof Medicine, Han~rd MedicalSchool, Boston, MA, USA.
distinguished plant scientist appeared without its customary accent on the final 'e' but was solemnly followed by the words 'Jim, I think this guy needs an accem'. Then there was the paper whose materials and methods section reported that the gels (none too sharp in my opinion) had been stained with 'Coomassie Blur'. And I raised my glass in gratitude and understanding to the undergraduate who lightened a recent exam-marking stint by writing: 'Antibodies are composed of two immunoglobulin light chains and two immunoglobulin dark chains.' By the way, if anyone can put my way a copy of the 'Wicked' Bible of 1632, so called because the printer succeeded in omitting 'not' from 'Thou shalt not commit adultery', I'd be jolly grateful.
ChristopherHowe Depm*mentof Biochemistry, Unilaersi~of Cambridge, TennisCouriRoad, Cambridge, UI¢CB2 IQW,
~ c l a n ' s compilation APracticalGuide to Human Cancer Genetics by S,V, Hodgson and E.R, Maher Cambridge University Press, 1993, £45,00 hbk/£19.95 pbk (258 pages) ISBN 0 521 40128 3 Inherited predisposition to cancer is becoming increasingly important, in terms of both research and clinical management, The past five years have seen the localization of many of the genes involved in family cancer syndromes. Some of&e~;~.":o.:i. q.:h :~s the AFCgene responsible for familial polyposis coil, have been cloned, and their function is beginning to be understood. More recently, there has been progress towards identifying genetic factors for some of the more common familial cancers, notably the BRCA1 locus, implicated in breast and ovarian cancer. These advances are having an impact on clinical practice. Predictive testing is now available for many syndromes, on the basis of genetic linkage or mutation analysis. Most regional dinical genetics services now "riGseP'rrMBeH 1993 VOL.9 NO. 9
',3c
have a consultant specializing in familial cancer, and many oncologists are becoming interested in inherited predisposition to cancer. This book is therelore timely. As the name suggests, it is a concise practical guide for clinical geneticists and oncologists, rather than a comprehensive treatise on all aspects of familial cancer. A general introduction and appendices cover the principles of cancer genetics, hut most of the volume is taken up with short accounts of the genetics of each cancer and the known~najor cancer p;edisposition syndromes (over 70 in all). In this respect, the coverage is comprehensive; there are sections on all file cancer syndromes I had ever heard of, and a great many I had not. In such a compact book it is impossible to cover
~]OOK []~EVIEWS every syndrome in great depth, and many entries simply give the diagnostic features of the syndrome together with key references from which more detailed information can be obtained. For the more important syndromes, however, details of screening and management are also discussed. I have no serious criticisms of the guide, but some reservations are perhaps worth mentioning. First, in such a rapidly changing field it is impossible for the information in any publication to be completely up to date: this is particularly true of the molecular genetics, less so the clinical details. Another limitation is that this type of guide gives a very warped impression of the relative numerical importance of different cancer syndromes. Most of the syndromes discussed are exceedingly rare: some
cases have been reported in just one or two families and are of interest only to a few specialists. Genetic predispositions to the more common cancers, such as breast or colorectal cancer, affect many more people and are relevant to most oncologists. Mthough the genetics of these common cancers is still only poorly understood, it is likely that genetic predisposition may play a part in at least 10% of sufferers. Another difficult area is screening. Various types of cancer screening are integral in the management of much familial cancer, but there is often lime evidence that such programs are effective or optimal. For example, in the section on breast cancer, it is stated that regular mammographic screening is likely to reduce mortality from the disease in women at high risk. While it is true that
and h'berfles DNA on Trial: Genetic Identification and Criminal Justice
editedbyPaulR,Billings Cold Spring Harbor Laboratory Press, 1992. $55.00 hbk (viii + 154 pages) ISBN 0 87969 381 DNA on Trial: Genetic Identification and Criminal Justice is based on papers given at a symposium of the American Association for the Advancement of Science, initiated by the Human Genetics Committee of the Council for Responsible Genetics. In addition to the eight papers presented, there is an introduction by the editor and a concluding policy statement by the sponsors, in which they call for strong restrictions on DNA banks (and take a gratuitous swipe at behavioral genetics). The articles are diverse, and the views expressed therein often disagree with one another. In the chapter 'Reliability of statistical estimates in forensic DNA typing', Budowle, Monson and Wooley point out that the rarity of VNTR types in all populations means that the estimated likelihoods of identical combinations occurring by chance are robust enough to be fully suitable for forensic purposes. In his paper 'Statistical issues in DNA identification', Berry provides an elementary exposition of Bayes' Rule, and suggests its use in the courts. Baird's contribution, 'Forensic DNA in the trial court 1990-1992: a brief history', reviews court cases and points out the value of DNA testing in exonerating the innocent. In 'Public policy for forensic DNA analysis: the model of New York State', Kotval asks for high technical standards and restrictions on DNA banking.
Most of the other authors take a dim view of the use of DNA analysis. Rabinow's piece, 'Galton's regret: of types and individuals', urges a search for individually distinct genotypes 'not linked to race and temperament', without seeming to realize that muliilocus VNTR genotypes come very close to this ideal. Moreover, the author chides Gahon for being disappointed that fingerprints 'reveal nothing about individual character or group affiliation', and would leave him 'where he belongs - in purgatory'. In 'Reasons for doubt: legal issues in the use of DNA identification techniques', Shultz notes that the legal system is not designed simply to search for truth but also includes procedural justice, and emphasizes the merits of the adversarial system as opposed to reliance on experts. Bereano deals with 'The impact of DNA-based identification systems on civil liberties', arguing that the cost in civil liberties may well outweigh any benefits from precision of identification. In the chapter 'Genetics, race, and crime: recurring seduction to a false precision', Duster discusses the high rate of incarceration of black people in our society; a serious problem, of course, but hardly one germane to this volume. What does one conclude from reading the book~ Here are a few reactions. The ability of the courts to arrive at probable truth from DNA evidence is not impressive. The cases often become TIGSEt'TEMBEt~1993 YOU 9 NO. 9
~31
mammography is commonly used in the management of women in breast cancer families, the results from randomized trials suggest that screening of women under the age of 50 has little or no impact on mortality from the disease. Clearly, one cannot, in such a concise book, discuss all the uncertainties in managing these syndromes, but the reader should be made aware that such uncertainties exist. On the whole, however, this is a well-researched book, attractively put together, that should prove invaluable to the practising clinical geneticist or oncologist.
Douglas F.,aston Instituteof CancerResearch, Belmont, Surrey, UKSM2 5NG.
ensnared in arguments over admissibility of the evidence. Much of the inconsistency is caused by mixed signals from opposing genetic experts testifying in trials; for some, winning the case seems more important than trying to find the truth. Those authors who deplore the use of DNA analysis in forensics do not, l believe, give enough emphasis to its value in exonerating the innocent, sometimes after years of mistaken incarceration, there is a curious reluctance of the courts to accept we!lformulated probability analysis, despite themselves continually making subjective probability judgements, for example, as to whether a witness is lying. I don't know the frequency of (convincing) liars, but it surely is a lot higher than, say, the 10"s chance of error that might he calculated from VNTRdata. Finally, very little information is given about techniques or frequency data. This may be just as well, for data are accumulating so rapidly that the book would have been obsolete before it was even published. The argument that forensic use of DNA will lead down the slippery slope to racism is spurious. We are already in the situation where every individual's VNTR genotype is almost unique and characterization of a very few more loci will remove even this uncertainty. Then the population subgroup and race of the tested individual will be truly irrelevam. It is well known - and repeatedly emphasized by the guru of the 'responsibles', Richard Lewontin - that for molecular markers, differences between individuals greatly exceed the (mean) differences between races. A recent study [N.J. Risch and B. Devlin (1992) Science 255, 717-720] found no four- or five-locus VNTRmatches among
and cancer genetics. It is suitable for the uninitiated but informed lay person, and for the high-school student, college student and novice medical student. One aim of Cancer Watch is to 'cuhivate an appreciation for bioscience in highschool and college students', and perhaps encourage them to enter biomedical research. Perhaps more biographies of researchers, such as the one of Dr Nori, would bring a personal
Freak scene PlantGeneResearch:CellOrgandies editedby R.G.Herrmann Springer-Vedag, 1992. DM 229.00 hbk (vii + 467 pages) ISBN 3 211 82264 X For a long time I introduced lectures and seminars on chloroplast DNA by pointing out that it encoded the most abundant protein in the world (the large subunit of ribulose b/s-phosphate carboxylase, for the uninitiated). It shames me to admit that this was partly owing to some kind of paranoia that organelle DNA was seen by many as a mildly frivolous side-issue. So it comforted me to see that I wasn't the only one feeling this way, on reading in Reinhold Herrmann's preface to
Plant Gene Research: Cell O~anelles that 'Non-Mendelian inheritance was considered a research sideline - if not a I"reak - by most geneticists...' (While we're talking about sidelines, I might mention that, at least in the 17th and 18th centuries, 'freak' meant not only something unusual, but also, quite specific:ally, a variegated plant. So John Milton wrote in his poem Lycldas of '...the pansy freaked with jet...' Appropriate then, that the subject of organelle genetics should be referred to as freakish when the first insights into it came from the work of Baur and Correns on the inheritance of variegation in plants. But enough of my attempts at erudite footnotes.) The book sets out to give an 'up-todate account' of the subject, 'indicative of its growth, vitality and momentum', and I believe it succeeds. If I had to find a criticism, it would probably be with the title of Cell Organelles, since the book essentially limits itself to plastids and mitochondria, although there is one chapter on glyoxysomes and peroxisomes. The other organelles don't really get a look in. Within that restriction, the coverage is generally good, ranging from classical through to molecular genetics, from evolution to the control of gene expre~ion, and from algae (concentrating on Chlamydomonas) to Zea. Certainly, the book will be invaluable to anyone who, like me, gives
final-year undergraduate lectures on the molecular genetics of plastids and plant mitochondria (not to mention the undergraduate who has to sit through them). In fact, anyone working in this field of research should find this a useful and authoritative set of reviews, and I am happy to recommend it. Presentation of the volume is generally good, although the language of some authors is a little quirky. Diagrams are clear and typos are kept to a mininmm. My friends chide me for looking out for typos, but collecting them can be fun. Well it's got to be better than trainspotting, and I haven't got an anorak, anyway. I remember a book of conference abstracts where the name of a
touch and be an inspiration to students of science.
ChaffsEng CRCHuman CancerGeneticsResearchGl~up, Departmentof Pathology, Unitkorsi(t,of Cambridge, Cambridge, UKCB21QP,.and Division of Medical Oncolo~, Dana-Father CancerInstitute, Departmentof Medicine, Han~rd MedicalSchool, Boston, MA, USA.
distinguished plant scientist appeared without its customary accent on the final 'e' but was solemnly followed by the words 'Jim, I think this guy needs an accem'. Then there was the paper whose materials and methods section reported that the gels (none too sharp in my opinion) had been stained with 'Coomassie Blur'. And I raised my glass in gratitude and understanding to the undergraduate who lightened a recent exam-marking stint by writing: 'Antibodies are composed of two immunoglobulin light chains and two immunoglobulin dark chains.' By the way, if anyone can put my way a copy of the 'Wicked' Bible of 1632, so called because the printer succeeded in omitting 'not' from 'Thou shalt not commit adultery', I'd be jolly grateful.
ChristopherHowe Depm*mentof Biochemistry, Unilaersi~of Cambridge, TennisCouriRoad, Cambridge, UI¢CB2 IQW,
~ c l a n ' s compilation APracticalGuide to Human Cancer Genetics by S,V, Hodgson and E.R, Maher Cambridge University Press, 1993, £45,00 hbk/£19.95 pbk (258 pages) ISBN 0 521 40128 3 Inherited predisposition to cancer is becoming increasingly important, in terms of both research and clinical management, The past five years have seen the localization of many of the genes involved in family cancer syndromes. Some of&e~;~.":o.:i. q.:h :~s the AFCgene responsible for familial polyposis coil, have been cloned, and their function is beginning to be understood. More recently, there has been progress towards identifying genetic factors for some of the more common familial cancers, notably the BRCA1 locus, implicated in breast and ovarian cancer. These advances are having an impact on clinical practice. Predictive testing is now available for many syndromes, on the basis of genetic linkage or mutation analysis. Most regional dinical genetics services now "riGseP'rrMBeH 1993 VOL.9 NO. 9
',3c
have a consultant specializing in familial cancer, and many oncologists are becoming interested in inherited predisposition to cancer. This book is therelore timely. As the name suggests, it is a concise practical guide for clinical geneticists and oncologists, rather than a comprehensive treatise on all aspects of familial cancer. A general introduction and appendices cover the principles of cancer genetics, hut most of the volume is taken up with short accounts of the genetics of each cancer and the known~najor cancer p;edisposition syndromes (over 70 in all). In this respect, the coverage is comprehensive; there are sections on all file cancer syndromes I had ever heard of, and a great many I had not. In such a compact book it is impossible to cover
~]OOK []~EVIEWS every syndrome in great depth, and many entries simply give the diagnostic features of the syndrome together with key references from which more detailed information can be obtained. For the more important syndromes, however, details of screening and management are also discussed. I have no serious criticisms of the guide, but some reservations are perhaps worth mentioning. First, in such a rapidly changing field it is impossible for the information in any publication to be completely up to date: this is particularly true of the molecular genetics, less so the clinical details. Another limitation is that this type of guide gives a very warped impression of the relative numerical importance of different cancer syndromes. Most of the syndromes discussed are exceedingly rare: some
cases have been reported in just one or two families and are of interest only to a few specialists. Genetic predispositions to the more common cancers, such as breast or colorectal cancer, affect many more people and are relevant to most oncologists. Mthough the genetics of these common cancers is still only poorly understood, it is likely that genetic predisposition may play a part in at least 10% of sufferers. Another difficult area is screening. Various types of cancer screening are integral in the management of much familial cancer, but there is often lime evidence that such programs are effective or optimal. For example, in the section on breast cancer, it is stated that regular mammographic screening is likely to reduce mortality from the disease in women at high risk. While it is true that
and h'berfles DNA on Trial: Genetic Identification and Criminal Justice
editedbyPaulR,Billings Cold Spring Harbor Laboratory Press, 1992. $55.00 hbk (viii + 154 pages) ISBN 0 87969 381 DNA on Trial: Genetic Identification and Criminal Justice is based on papers given at a symposium of the American Association for the Advancement of Science, initiated by the Human Genetics Committee of the Council for Responsible Genetics. In addition to the eight papers presented, there is an introduction by the editor and a concluding policy statement by the sponsors, in which they call for strong restrictions on DNA banks (and take a gratuitous swipe at behavioral genetics). The articles are diverse, and the views expressed therein often disagree with one another. In the chapter 'Reliability of statistical estimates in forensic DNA typing', Budowle, Monson and Wooley point out that the rarity of VNTR types in all populations means that the estimated likelihoods of identical combinations occurring by chance are robust enough to be fully suitable for forensic purposes. In his paper 'Statistical issues in DNA identification', Berry provides an elementary exposition of Bayes' Rule, and suggests its use in the courts. Baird's contribution, 'Forensic DNA in the trial court 1990-1992: a brief history', reviews court cases and points out the value of DNA testing in exonerating the innocent. In 'Public policy for forensic DNA analysis: the model of New York State', Kotval asks for high technical standards and restrictions on DNA banking.
Most of the other authors take a dim view of the use of DNA analysis. Rabinow's piece, 'Galton's regret: of types and individuals', urges a search for individually distinct genotypes 'not linked to race and temperament', without seeming to realize that muliilocus VNTR genotypes come very close to this ideal. Moreover, the author chides Gahon for being disappointed that fingerprints 'reveal nothing about individual character or group affiliation', and would leave him 'where he belongs - in purgatory'. In 'Reasons for doubt: legal issues in the use of DNA identification techniques', Shultz notes that the legal system is not designed simply to search for truth but also includes procedural justice, and emphasizes the merits of the adversarial system as opposed to reliance on experts. Bereano deals with 'The impact of DNA-based identification systems on civil liberties', arguing that the cost in civil liberties may well outweigh any benefits from precision of identification. In the chapter 'Genetics, race, and crime: recurring seduction to a false precision', Duster discusses the high rate of incarceration of black people in our society; a serious problem, of course, but hardly one germane to this volume. What does one conclude from reading the book~ Here are a few reactions. The ability of the courts to arrive at probable truth from DNA evidence is not impressive. The cases often become TIGSEt'TEMBEt~1993 YOU 9 NO. 9
~31
mammography is commonly used in the management of women in breast cancer families, the results from randomized trials suggest that screening of women under the age of 50 has little or no impact on mortality from the disease. Clearly, one cannot, in such a concise book, discuss all the uncertainties in managing these syndromes, but the reader should be made aware that such uncertainties exist. On the whole, however, this is a well-researched book, attractively put together, that should prove invaluable to the practising clinical geneticist or oncologist.
Douglas F.,aston Instituteof CancerResearch, Belmont, Surrey, UKSM2 5NG.
ensnared in arguments over admissibility of the evidence. Much of the inconsistency is caused by mixed signals from opposing genetic experts testifying in trials; for some, winning the case seems more important than trying to find the truth. Those authors who deplore the use of DNA analysis in forensics do not, l believe, give enough emphasis to its value in exonerating the innocent, sometimes after years of mistaken incarceration, there is a curious reluctance of the courts to accept we!lformulated probability analysis, despite themselves continually making subjective probability judgements, for example, as to whether a witness is lying. I don't know the frequency of (convincing) liars, but it surely is a lot higher than, say, the 10"s chance of error that might he calculated from VNTRdata. Finally, very little information is given about techniques or frequency data. This may be just as well, for data are accumulating so rapidly that the book would have been obsolete before it was even published. The argument that forensic use of DNA will lead down the slippery slope to racism is spurious. We are already in the situation where every individual's VNTR genotype is almost unique and characterization of a very few more loci will remove even this uncertainty. Then the population subgroup and race of the tested individual will be truly irrelevam. It is well known - and repeatedly emphasized by the guru of the 'responsibles', Richard Lewontin - that for molecular markers, differences between individuals greatly exceed the (mean) differences between races. A recent study [N.J. Risch and B. Devlin (1992) Science 255, 717-720] found no four- or five-locus VNTRmatches among