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Prostate cancer segregation analyses using 4390 families from UK and Australian population‐based studies
Author(s) -
MacInnis Robert J.,
Antoniou Antonis C.,
Eeles Rosalind A.,
Severi Gianluca,
Guy Michelle,
McGuffog Lesley,
Hall Amanda L.,
O'Brien Lynne T.,
Wilkinson Rosemary A.,
Dearnaley David P.,
ArdernJones Audrey T.,
Horwich Alan,
Khoo Vincent S.,
Parker Christopher C.,
Huddart Robert A.,
McCredie Margaret R.,
Smith Charmaine,
Southey Melissa C.,
Staples Margaret P.,
English Dallas R.,
Hopper John L.,
Giles Graham G.,
Easton Douglas F.
Publication year - 2010
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.20433
Subject(s) - genetics , multifactorial inheritance , allele , family aggregation , genetic model , population , prostate cancer , confidence interval , inheritance (genetic algorithm) , biology , polygene , cancer , demography , gene , quantitative trait locus , medicine , genotype , single nucleotide polymorphism , environmental health , sociology
Familial aggregation of prostate cancer is likely to be due to multiple susceptibility loci, perhaps acting in conjunction with shared lifestyle risk factors. Models that assume a single mode of inheritance may be unrealistic. We analyzed genetic models of susceptibility to prostate cancer using segregation analysis of occurrence in families ascertained through population‐based series totaling 4390 incident cases. We investigated major gene models (dominant, recessive, general, X‐linked), polygenic models, and mixed models of susceptibility using the pedigree analysis software MENDEL. The hypergeometric model was used to approximate polygenic inheritance. The best‐fitting model for the familial aggregation of prostate cancer was the mixed recessive model. The frequency of the susceptibility allele in the population was estimated to be 0.15 (95% confidence interval (CI) 0.11–0.20), with a relative risk for homozygote carriers of 94 (95% CI 46–192), and a polygenic standard deviation of 2.01 (95% CI 1.72–2.34). These analyses suggest that one or more genes having a strong recessively inherited effect on risk, as well as a number of genes with variants having small multiplicative effects on risk, may account for the genetic susceptibility to prostate cancer. The recessive component would predict the observed higher familial risk for siblings of cases than for fathers, but this could also be due to other factors such as shared lifestyle by siblings, targeted screening effects, and/or non‐additive effects of one or more genes. Genet. Epidemiol . 34:42–50, 2010. © 2009 Wiley‐Liss, Inc.