Atlas: Segregation analyses of 1476 population-based Australian families affected by prostate cancer by Jisheng Cui

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Australasian Biometrics and New Zealand Statistical Association Joint Conference 2001
December 10-13, 2001
Park Royal Hotel
Christchurch, New Zealand

Organizers
David Baird, Dave Saville, Harold Henderson, Peter Johnstone, Marco Reale, Irene Hudson, Julian Visch, Roger Littlejohn

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Segregation analyses of 1476 population-based Australian families affected by prostate cancer
by
Jisheng Cui
The University of Melbourne
Coauthors: Jisheng Cui, Margaret P. Staples, John L. Hopper, Dallas R. English, Margaret R. E. McCredie, Graham G. Giles

Segregation analyses aim to detect genetic factors that have a major effect on individual's risk of disease and describe them in terms of mode of inheritance, age-specific cumulative risk (penetrance), and allele frequency. We conducted single- and two-locus segregation analyses of data from 1476 men with prostate cancer diagnosed at age <70 years and ascertained through population registries in Melbourne, Sydney and Perth, Australia, and from their brothers, fathers and both maternal and paternal uncles. Estimation and model selection were based on asymptotic likelihood theory and were performed through use of the software MENDEL. All two-locus models gave better fits than single-locus models, even if uncles were excluded or if we censored data (age and disease status) for relatives at 1992, when prostate-specific-antigen testing started to have a major impact on incidence of prostate cancer in Australia. Among the genetic models that we considered, the best fitting ones included a dominantly inherited increased risk that was greater, in multiplicative terms, at younger ages, as well as a recessively or X-linked increased risk that was greater in multiplicative terms, at older ages. The recessive and X-linked effects were strongly confounded, and it was not possible to fit them together. Penetrance to age 80 years was about 70% (95% confidence interval [CI] 57% - 85%) for the dominant effect and virtually 100% for the recessive or X-linked effects. About 1/30 (95% CI 1/80 to 1/12) men would carry the dominant risk, and 1/140 (95% CI 1/220 to 1/90) the recessive risk or 1/200 (95% CI 1/380 to 1/100) the X-linked risk. Within discussed limitations, these analyses confirm the genetic heterogeneity, of prostate cancer susceptibility, that is becoming evident from linkage analyses, and may aid future efforts in gene discovery.

Date received: August 31, 2001