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Identification of a prostate cancer susceptibility gene on chromosome 5p13q12 associated with risk of both familial and sporadic disease
journal contribution
posted on 2023-05-16, 22:27 authored by Liesel FitzgeraldLiesel Fitzgerald, Patterson, B, Russell Thomson, Polanowski, AM, Quinn, SJ, Brohede, J, Thornton, T, Challis, D, David MackeyDavid Mackey, Terry DwyerTerry Dwyer, Simon James FooteSimon James Foote, Hannan, GN, Jim Stankovich, McKay, JD, Joanne DickinsonJoanne DickinsonGenetic 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.
History
Publication title
European Journal of Human GeneticsVolume
17Pagination
368-377ISSN
1018-4813Department/School
Menzies Institute for Medical ResearchPublisher
Nature Publishing GroupPlace of publication
United KingdomRights statement
Copyright 2009 Macmillan PublishersRepository Status
- Restricted