ReferenceRRK2553

UKGPCS

UK Genetic Prostate Cancer Study

Research Summary

Molecular approaches to the understanding of neoplasia have revealed that multiple genetic alterations are involved in the development of the malignant phenotype (Weinberg 1989). Often the changes that occur in genes in cancer cells in sporadic cancers are the same as those that occur in cancers due to an inherited predisposition. The only difference between sporadic and inherited forms of the same cancer type is that those cancers occurring due to an inherited predisposition involve an initiating abnormal genetic event in the germline. Cancers that are due to an inherited disposition therefore tend to occur at younger ages than the sporadic 4orms of the same cancer. Genetic targets in this multistep pathway have have been identified by the study of somatic genetic alterations and identification of the genetically inherited defects in families with a predisposition to the development of certain cancers.Examples have now been found where the inherited abnormality in cancerfamilies is also seen in sporadic turnouts of the same phenotype. One example is the tumour supressor gene p53 which has been shown to be mutated in many tumour types (Nigro 1989) and is the cause of at least some cases of the Li-Fraumeni syndrome (Malkin 1990; Srivastava 1990).There is evidence for the familial aggregation of prostate cancer. In 1960 Woolf studied the first degree relatives of prostate cancer cases in the Utah Mormon population in the U.S.A. By studying death certificates and comparing them with age-matched controls he found that first degree relatives of cases had a threefold increased risk of prostate cancer. Results from other studies are tabulated below: UII.’5Brothman AR. Peehl DM. Pate) AM.et al (1990) Cancer Res. 50 3795-3803Cannon L. Bishop Dt. Skolnick M et 81(1982) Cancer Surveys 1 47-69.Carter E3S. Ewing CM. Ward WS. et al (1990) Proc Nail Acad Sci USA. 878751 -55.Ghadirian P. Cadotte M. Lacroix A. et aI (1991) Prostate 19 43-52.Krain LS (1974) Prey Med. 3 154-9.Malkin D. Li FP. Strong LC. et a! (1990) Science 250 1233-1238.Meikle AW. Smith JA. & West DW. (1985). Prostate 6 121-8.Morganti 0. Gianferrari L. Cresseri A. et al. (1956) Ada Genetica Statistica 6304-5.Nigro i. Baker Si. Preisinger AC at al (1989) Nature 342 705-708.Schuman LM. Mandel J. Blackard C. at a!. (1977) Cancer Treat. Rep. 61181-186.Spitz MR. Currier RD. Fueger ii. eta! (1991) J Urol 146 1305-7.Srivastava S. Zou Z. Pirollo K. et al (1990) Nature 348 747-9.Steele R. Lees REM. Kraus AS. et aI (1971). .J Chronic Dis. 24 29.Steinberg OS.. Carter BS. Beaty TH. et al. (1990) Prostate 17 337-47.Weinberg RA (1989) Cancer Res. 45 1437-43.Woolf CM (1960) Cancer 13 739-44.

Research Overview
PI Name James - ND
Speciality
Sponsor Institute of Cancer Research
Project Status Open
Proposed End Date 31/12/2017
Study Run through CRF? No
Recruitment so far 12