Osteosarcoma (OS) and Ewing sarcoma (ES) are highly malignant tumours arising in bone but with different cells of origin. OS and ES show similar remarkable patterns when the incidence is plotted by age. There are sharp peaks in incidence that coincide with growth spurts during adolescence. This pattern suggests that the rapid bone growth during adolescence creates a very vulnerable period when cells are more likely to become malignant. However, the path from a normal cell to becoming a malignant cell is a multi-step process. The malignant changes that occur to cells during the adolescent growth spurt are almost certainly preceded by earlier (pre-malignant) changes which might occur during other periods of rapid growth, for example, in the developing baby before birth, during infancy and/or during the mid-childhood growth spurt. Malignant bone tumours are a major cause of death in young people but we know very little about the causes. The challenge is to try to identify internal (e.g. hormonal and genetic) factors and external environmental factors (e.g. viruses, diet, physical exercise, toxic chemicals, radiation) which bring about changes in target cells eventually leading to cancer formation. If we can do this in relation to particularly vulnerable periods of development in a young person's life, this could ultimately lead to prevention.

A major problem in carrying out studies of possible causes is that OS and ES are rare. In order to recruit a sufficient number of cases to enable risk factors to be identified with confidence and within a reasonable time period, it will be necessary to carry out an international study. An international working group has been established to consider research priorities and to develop a protocol for such a study. A draft protocol has been agreed. It is essential to conduct a pliot study as a necessary forerunner to the full-scale study. The BCRT has funded Professors Jillian Birch and Patricia McKinney to carry out a 2-centre pilot involving interviews with cases, depending on age, mothers and fathers of OS and ES patients aged 0-24 years from Manchester and Leeds and surrounding regions. Blood or saliva samples will be collected and relevant medical records abstracted. The pilot study itself will not provide answers about causes. However, it will provide crucial information on: the likely proportions of cases and their parents which can be recruited, the likelihood that families will consent to give samples for molecular genetic studies; the proportions of cases and parents that do or do not have particular characterisitics of interest; the availability and completeness of relevant medical records.

All this information is essential to work out how many participating countries and centres and patients from each centre will be needed for a full-scale study. Problems in recruiting families and difficulties with the phrasing of particular questions can be identified and rectified. It is also important to identify and rectify any problems encountered with locating and abstracting medical records. Information from the pilot will enable the final protocol to be developed. In addition, the hypothesis-generating epidemiological study funded by the BCRT (McNally and colleagues) together with current work on national and regional cancer data from Professor Birch’s and McKinney’s units will help to develop and refine the hypotheses for the main case-control study. Although definitive answers will not be forthcoming from the pilot, the information and samples will be added to the main study.

Professor Jillian Birch, University of Manchester