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Clinical and Biological Basis of Lung Cancer Prevention.

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Clinical and Biological Basis of Lung Cancer Prevention. Martinet Y, Hirsch FR, Martinet N, Vignaud J-M, Mulshine JL, eds. (Pp 322). Switzerland: Birkhäuser Verlag, 1998. ISBN 3-7643-5778-9.

This is a comprehensive and technically detailed book which will, I think, be of value to laboratory workers and perhaps some interested clinicians who wish to have authoritative accounts of research into the application of oncological biology to the early detection and, to a lesser extent, the prevention of lung cancer.

In 1996 the International Association for the Study of Lung Cancer (IASLC) sponsored two workshops on lung cancer prevention, the first focusing on clinical studies and the second—the subject of this book—focusing on basic laboratory work which was held in Nancy in France. This volume consists of 30 separate papers delivered at the workshop and edited for publication.

Although the title of the book emphasises prevention, to my mind the bulk of it essentially looks at laboratory investigations of risk factors and changes in the bronchial epithelium and the early evolution of tumours which might, with luck, be translated into strategies for early detection of lung cancer rather than its prevention. Of course this is a hugely important problem; 90% of lung cancers are caused by tobacco inhalation but it is unknown why only about 15% of smokers are susceptible to malignant change. Sadly, it is widely recognised that primary prevention—largely a matter of social policy and public pressure—is failing even in the developed world and, with the unopposed expansion of tobacco marketing in the third world, from a global perspective the lung cancer epidemic is set to continue for the foreseeable future and to be concentrated in communities where the prospects of using elaborate techniques for early detection or protection are bleak.

It is also well recognised that the lung cancer screening programmes using presently available techniques such as plain radiography and sputum cytology are not cost effective (unlike cancer of the cervix and cancer of the breast). This situation may change in some communities and there is now interest in portable spiral computed tomographic scanning, possibly coupled with the examination of chromosomal abnormalities in sputum in high risk individuals, which may to a certain extent bridge the gap between what is presently achievable and what the articles in this book hold out as tantalising promises.

The scope of laboratory work described here is wide. Amongst others, those that came to my attention included genetic subsectibility, chemoprevention, pre-malignant changes, inhibitory growth factors, and fluoroscopic bronchoscopy. For genetic susceptibility, I learnt that polymorphisms of a regulatory gene might determine the inducibility of two forms of cytochrome p450 by tobacco smoke which leads to a variable ability of tobacco smoke to convert pro-carcinogens into carcinogenic metabolites. Other polymorphisms may add to these risks. Sadly, the theoretical promise of primary chemoprevention using substances thought to inhibit carcinogenesis (β-carotenes and α-tocopherol) do not seem to have been borne out in clinical trials (Pastorino and Sasco).

Running throughout many chapters is the concept that there is a cascade of pre-malignant changes in bronchial epithelium involving genetic damage and which, if detected at an early stage, might allow more effective treatment. However, this hypothesis —although promising for squamous carcinoma—seems to be supported less strongly with respect to adenocarcinoma and small cell carcinoma. The particular value of studying these early genetic abnormalities is, it seems to me, that they may be reflected in sputum samples, and with a high proportion of carcinomas now presenting in the UK in ex-smokers as opposed to present smokers, in whom of course prevention is inappropriate, early treatment might be possible. A chapter discussing fluorescence bronchoscopy (Lam McAulay) shows that early lesions can be identified, but this particular volume does not include data showing that early detection in this way yields better survival figures. Not surprisingly, because of the possibility of improved therapy, there are papers on inhibitory growth factors such as metalloproteinases (Vignaudet al) and neuropeptides (Seckel and Rozengurt) in relation to small cell lung cancer which demonstrate how powerful synthetic inhibitors of these substances might be.

I came away from reading this book with a strong impression of the ingenuity and the variety of potential anti-cancer strategies that are being studied. It would be far too optimistic to suppose that the subjects of all of these 30 chapters will in due course be shown to be fundamental to a novel and important way of either detecting lung cancer earlier, preventing it, or inhibiting it. But only a pessimist would suppose that nowhere in this comprehensive book is there a discussion of an approach which will eventually be found to be clinically useful and justify the huge research effort so carefully described in these pages.—MM