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Identification of a prostate cancer susceptibility gene on chromosome 5p13q12 associated with risk of both familial and sporadic disease

Citation

Fitzgerald, LM and Patterson, B and Thomson, RJ and Polanowski, AM and Quinn, SJ and Brohede, J and Thornton, T and Challis, D and Mackey, DA and Dwyer, T and Foote, SJ and Hannan, GN and Stankovich, J and McKay, JD and Dickinson, JL, Identification of a prostate cancer susceptibility gene on chromosome 5p13q12 associated with risk of both familial and sporadic disease, European Journal of Human Genetics, 17 pp. 368-377. ISSN 1018-4813 (2009) [Refereed Article]

Copyright Statement

Copyright 2009 Macmillan Publishers

DOI: doi:10.1038/ejhg.2008.171

Abstract

Genetic heterogeneity is a difficulty frequently encountered in the search for genes conferring susceptibility to prostate cancer. To circumvent this issue, we selected a large prostate cancer pedigree for genome-wide linkage analysis from a population that is genetically homogeneous. Selected cases and first-degree relatives were genotyped with Affymetrix 10K SNP arrays, identifying a 14 Mb haplotype on chromosome 5 (5p13–q12) inherited identical-by-descent (IBD) by multiple cases. Microsatellite genotyping of additional deceased case samples confirmed that a total of eight cases inherited the common haplotype (P = 0.0017). Re-sequencing of eight prioritised candidate genes in the region in six selected individuals identified 15 SNPs segregating with the IBD haplotype, located within the ITGA2 gene. Three of these polymorphisms were selected for genotyping in an independent Tasmanian data set comprising 127 cases with familial prostate cancer, 412 sporadic cases and 319 unaffected controls. Two were associated with prostate cancer risk: rs3212649 (OR = 1.67 (1.07–2.6), P = 0.0009) and rs1126643 (OR = 1.52 (1.01–2.28), P = 0.0088). Significant association was observed in both familial and sporadic prostate cancer. Although the functional SNP remains to be identified, considerable circumstantial evidence, provided by in vivo and in vitro studies, supports a role for ITGA2 in tumour development.

Item Details

Item Type:Refereed Article
Keywords:genetic, susceptibility, prostate, cancer, risk
Research Division:Medical and Health Sciences
Research Group:Oncology and Carcinogenesis
Research Field:Cancer Genetics
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
Author:Fitzgerald, LM (Dr Liesel Fitzgerald)
Author:Patterson, B (Dr Briony Patterson)
Author:Thomson, RJ (Dr Russell Thomson)
Author:Polanowski, AM (Ms Andrea Polanowski)
Author:Quinn, SJ (Dr Stephen Quinn)
Author:Mackey, DA (Professor David Mackey)
Author:Dwyer, T (Professor Terry Dwyer)
Author:Foote, SJ (Professor Simon Foote)
Author:Stankovich, J (Dr Jim Stankovich)
Author:McKay, JD (Dr James McKay)
Author:Dickinson, JL (Associate Professor Joanne Dickinson)
ID Code:53900
Year Published:2009 (online first 2008)
Web of Science® Times Cited:20
Deposited By:Menzies Institute for Medical Research
Deposited On:2009-01-20
Last Modified:2016-11-17
Downloads:0

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