Segregation analyses of 1,476 population-based Australian families affected by prostate cancer

Cui J, Staples MP, Hopper JL, English DR, McCredie MR, Giles GG (2001) Segregation analyses of 1,476 population-based Australian families affected by prostate cancer. Am J Hum Genet 68:1207-1218

Segregation analyses aim to detect genetic factors that have a major effect on an individual's risk of disease and to 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 1,476 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="" lineal="" 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="" did="" single-locus="" models,="" even="" if="" lineal="" 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="" the="" 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="" inherited="" 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="" approximately="" 70%="" (95%="" confidence="" interval="" [ci]="" 57%-85%)="" for="" the="" dominant="" effect="" and="" virtually="" 100%="" for="" the="" recessive="" and="" x-linked="" effects.="" approximately="" 1/30="" (95%="" ci="" 1/80-1/12)="" men="" would="" carry="" the="" dominant="" risk,="" and="" 1/140="" (95%="" ci="" 1/220-1/90)="" would="" carry="" the="" recessive="" risk="" or="" 1/200="" (95%="" ci="" 1/380-1/100)="" would="" carry="" 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="" they="" may="" aid="" future="" efforts="" in="" gene="">