Abstract
Prostate cancer (PCa) is the most frequently diagnosed cancer in men worldwide and is likely to be caused by a number of genes with different modes of inheritance, population frequencies and penetrance. The objective of this study was to assess the familial aggregation of PCa in a sample of 1,546 nuclear families ascertained through an affected father and diagnosed during 1988–1993, from the unique, founder population-based resource of the Finnish Cancer Registry. Segregation analysis was performed for two cohorts of 557 early-onset and 989 late-onset families evaluating residual paternal effects and assuming that age at diagnosis followed a logistic distribution after log-transformation. The results did not support an autosomal dominant inheritance as has been reported in many of the hospital-based prostatectomy series. Instead, it confirmed the existence of hereditary PCa in the Finnish population under a complex model that included a major susceptibility locus with Mendelian recessive inheritance and a significant paternal regressive coefficient that is indicative of a polygenic/multifactorial component. The strengths of our study are the homogenous Finnish population, large epidemiological population-based data, histologically confirmed cancer diagnosis done before the PSA-era in Finland and registry based approach. Our results support the evidence that the inheritance of PCa is controlled by major genes and are in line with the previous linkage studies. Moreover, this is the first time a recessive inheritance is suggested to fit PCa in all data even when divided to early and late-onset cohorts.
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Acknowledgments
The authors thank Riitta Vaalavuo for her excellent assistance. Dr. Erica Golemis of the Fox Chase Cancer Center provided beneficial comments on this manuscript. This study was financially supported by the Medical Research Fund of Tampere University Hospital, the Reino Lahtikari Foundation, the Finnish Cancer Organizations, the Sigrid Juselius Foundation and the Academy of Finland (grant no. 211123). The program package SAGE supported by the US Public Health Service Resource Grant RR03655 from Division of Research Resources, was used for the complex segregation analyses. This work was partially supported by the Intramural Research Program of the National Human Genome Research Institute, the National Institutes of Health (Contract Number N01-HG-55389). A.B.B-B, S.D. and L.O also received support from USPHS grant CA-06927 and an appropriation from the Commonwealth of Pennsylvania.
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Sanna Pakkanen and Agnes B Baffoe-Bonnie equally contributed to this work.
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Pakkanen, S., Baffoe-Bonnie, A.B., Matikainen, M.P. et al. Segregation analysis of 1,546 prostate cancer families in Finland shows recessive inheritance. Hum Genet 121, 257–267 (2007). https://doi.org/10.1007/s00439-006-0310-2
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DOI: https://doi.org/10.1007/s00439-006-0310-2