Abstract:
:A genetic epidemiologic investigation of breast cancer involving 389 breast cancer pedigrees including information on 14,721 individuals from the Icelandic population-based cancer registry is presented. Probands were women born in or after 1920 and reported to have breast cancer in the cancer registry. The average age of the 389 probands was 45.5 years (SD 8.92). Segregation analyses was performed evaluating residual maternal effects, a dichotomous cohort effect, and assuming the age at diagnosis followed a logistic distribution after log-transformation. Familial aggregation could be best explained by the inheritance of a high-risk allele leading to early onset breast cancer among the homozygotes, which represent approximately 2.6% of the population. A Mendelian codominant model was selected as the best fitting model, with an estimated age at diagnosis of 51.8 years among these high-risk homozygotes, 64.0 years for heterozygotes and 76.3 years for the low-risk genotype. The predicted cumulative risk for homozygote carriers of the high-risk allele is 32.2% by age 60, compared to 16.4% for heterozygotes and 5.0% for non-carriers of the same age. These predicted age profiles in the current study complement recent reports from Iceland of a majority of BRCA2 mutation carriers being diagnosed with breast cancer below the age of 50 years, and 60 years being the mean age at diagnosis for non-carriers. This model also predicted a high background risk of breast cancer for women in this population (estimated susceptibility gamma = 0.44 +/- 0.08). This implies that if carriers and non-carriers did not die of competing causes, the estimated risk of being diagnosed with breast cancer by age 80 years irrespective of carrier status is 11.4%.
journal_name
Genet Epidemioljournal_title
Genetic epidemiologyauthors
Baffoe-Bonnie AB,Beaty TH,Bailey-Wilson JE,Kiemeney LA,Sigvaldason H,Olafsdóttir G,Tryggvadóttir L,Tulinius Hdoi
10.1002/(SICI)1098-2272(200001)18:1<81::AID-GEPI6>subject
Has Abstractpub_date
2000-01-01 00:00:00pages
81-94issue
1eissn
0741-0395issn
1098-2272pii
10.1002/(SICI)1098-2272(200001)18:1<81::AID-GEPI6>journal_volume
18pub_type
杂志文章abstract::There has been a great interest and a few successes in the identification of complex disease susceptibility genes in recent years. Association studies, where a large number of single-nucleotide polymorphisms (SNPs) are typed in a sample of cases and controls to determine which genes are associated with a specific dise...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20041
更新日期:2005-02-01 00:00:00
abstract::Methods for genetic risk prediction have been widely investigated in recent years. However, most available training data involves European samples, and it is currently unclear how to accurately predict disease risk in other populations. Previous studies have used either training data from European samples in large sam...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.22083
更新日期:2017-12-01 00:00:00
abstract::The Framingham Heart Study data, as well as a related simulated data set, were generously provided to the participants of the Genetic Analysis Workshop 13 in order that newly developed and emerging statistical methodologies could be tested on that well-characterized data set. The impetus driving the development of nov...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.10285
更新日期:2003-01-01 00:00:00
abstract::GAW10 Problem 2 involves a simulated common disease defined by imposing a threshold, T, on a quantitative trait, Q1. Every individual with a value of Q1 > or = T (where T = 40) is defined as affected. Also thought to be associated with the disease as intervening variables are four other quantitative traits (Q2, Q3, Q4...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2272(1997)14:6<737::AID-GEPI29>
更新日期:1997-01-01 00:00:00
abstract::High-throughput sequencing data can be used to predict phenotypes from genotypes, and this corresponds to establishing a prognostic model. In extended pedigrees the relatedness of subjects provides additional information so that genetic values, fixed or random genetic components, and heritability can be estimated. At ...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21826
更新日期:2014-09-01 00:00:00
abstract::The recent successes of genome-wide association studies (GWAS) have renewed interest in genome environment wide interaction studies (GEWIS) to discover genetic factors that modulate penetrance of environmental exposures to human diseases. Indeed, gene-environment interactions (G × E), which have not been emphasized in...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21890
更新日期:2015-07-01 00:00:00
abstract::Construction of multifactorial disease models from epidemiological findings and their application to disease pedigrees for risk prediction is nontrivial for all but the simplest of cases. Multifactorial Disease Risk Calculator is a web tool facilitating this. It provides a user-friendly interface, extending a reported...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.22101
更新日期:2018-03-01 00:00:00
abstract::We have conducted a simulation study in small pedigrees to investigate the power to detect linkage and heterogeneity for a disorder due to either one of two independent disease loci. We have considered a highly polymorphic marker locus (PIC = 70%) linked to one disease locus and unlinked to the second. The power to de...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370070306
更新日期:1990-01-01 00:00:00
abstract::When testing for genetic effects, failure to account for a gene-environment interaction can mask the true association effects of a genetic marker with disease. Family-based association tests are popular because they are completely robust to population substructure and model misspecification. However, when testing for ...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20421
更新日期:2009-12-01 00:00:00
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journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370080408
更新日期:1991-01-01 00:00:00
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journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20514
更新日期:2010-09-01 00:00:00
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journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1032
更新日期:2001-11-01 00:00:00
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journal_title:Genetic epidemiology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1002/(SICI)1098-2272(1997)14:6<1097::AID-GEPI89
更新日期:1997-01-01 00:00:00
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journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370060505
更新日期:1989-01-01 00:00:00
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journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21871
更新日期:2015-02-01 00:00:00
abstract::Several approaches were taken to identify the loci contributing to the quantitative and qualitative phenotypes in the Genetic Analysis Workshop 12 simulated data set. To identify possible quantitative trait loci (QTL), the quantitative traits were analyzed using SOLAR. The four replicates identified as the "best repli...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.2001.21.s1.s732
更新日期:2001-01-01 00:00:00
abstract::With new technologies, multiple types of genomic data are commonly collected on a single set of samples. However, standard analysis methods concentrate on a single data type at a time and ignore the relationships between genes, proteins, and biochemical reactions that give rise to complex phenotypes. In this paper, we...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.21628
更新日期:2012-05-01 00:00:00
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journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20396
更新日期:2009-07-01 00:00:00
abstract::This paper describes a general genetic model which encompasses both autosomal and X-linked inheritance as submodels. It allows one to test for X-linked inheritance of a trait by comparing the likelihood of X-linked inheritance to the likelihood of the general genetic model. The general model is formulated as two loci,...
journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370010105
更新日期:1984-01-01 00:00:00
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journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370090503
更新日期:1992-01-01 00:00:00
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journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370120106
更新日期:1995-01-01 00:00:00
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journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20164
更新日期:2006-09-01 00:00:00
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journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370110108
更新日期:1994-01-01 00:00:00
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journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20543
更新日期:2010-12-01 00:00:00
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journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20036
更新日期:2005-01-01 00:00:00
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journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370060207
更新日期:1989-01-01 00:00:00
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journal_title:Genetic epidemiology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:1998-01-01 00:00:00
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journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20531
更新日期:2010-11-01 00:00:00
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journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.20558
更新日期:2011-02-01 00:00:00
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journal_title:Genetic epidemiology
pub_type: 杂志文章
doi:10.1002/gepi.1370050409
更新日期:1988-01-01 00:00:00