Linkage disequilibrium mapping of a breast cancer susceptibility locus near RAI/PPP1R13L/iASPP
Authors:
- Bjørn A Nexø,
- Ulla Vogel,
- Anja Olsen,
- Matte Nyegaard,
- Zuzanna Bukowy,
- Eszter Rockenbauer,
- Xiuqing Zhang,
- Cemile Koca,
- Mette Mains,
- Bettina Hensen,
- Anne Hedemand,
- Anette Kjeldgaard,
- Michał Stanisław Laska,
- Ole Raaschou-Nielsen,
- Søren Cold,
- Kim Overvad,
- Anne Tjønneland,
- Lars Bolund,
- Anders D. Børglum
Abstract
Background: Previous results have suggested an association of the region of 19q13.3 with several forms of cancer. In the present study, we investigated 27 public markers within a previously identified 69 kb stretch of chromosome 19q for association with breast cancer by using linkage disequilibrium mapping. The study groups included 434 postmenopausal breast cancer cases and an identical number of individually matched controls. Methods and Results: Studying one markerat a time, we found a region spanning the gene RAI (alias PPP1R13L or iASPP) and the 5′ portion of XPD to be associated with this cancer. The region corresponds to a haplotype block, in which there seems to be very limited recombination in the Danish population. Studying combinations of markers, we found that two to four neighboring markers gave the most consistent and strongest result. The haplotypes with strongest association with cancers were located in the gene RAI and just 3' to the gene. Coinciding peaks were seen in the region of RAI in groups of women of different age. In a follow-up to these results we sequenced 10 cases and 10 controls in a 44 kb region spanning the peaks of association. This revealed 106 polymorphisms, many of which were not in the public databases. We tested an additional 44 of these for association with disease and found a new tandem repeat marker, called RAI-3'd1, located downstream of the transcribed region of RAI, which was more strongly associated with breast cancer than any other marker we have tested (RR = 2.44 (1.41-4.23, p = 0.0008, all cases; RR = 6.29 (1.49-26.6), p = 0.01, cases up to 55 years of age). Conclusion: We expect the marker RAI-3'd1 to be (part of) the cause for the association of the chromosome 19q13.3 region's association with cancer.
- Record ID
- USL63e1a9242ba1442bbe48003bbe0242de
- Author
- Journal series
- BMC Medical Genetics, ISSN 1471-2350
- Issue year
- 2008
- Vol
- 9
- Pages
- 1-12
- Article number
- 56
- Keywords in English
- Breast Neoplasms; Chromosome Mapping; Genetic Markers; Female; Denmark; Breast Cancer
- ASJC Classification
- ;
- DOI
- DOI:10.1186/1471-2350-9-56 Opening in a new tab
- Handle.net URL
- hdl.handle.net/20.500.12128/524 Opening in a new tab
- Language
- eng (en) English
- License
- File
-
- File: 1
- Linkage disequilibrium mapping of a breast cancer susceptibility locus near RAI/PPP1R13L/iASPP, File Nexo_Linkage_disequilibrium_mapping_of_a_breast_cancer.pdf / 1 MB
- Nexo_Linkage_disequilibrium_mapping_of_a_breast_cancer.pdf
- publication date: 06-02-2024
- Linkage disequilibrium mapping of a breast cancer susceptibility locus near RAI/PPP1R13L/iASPP, File Nexo_Linkage_disequilibrium_mapping_of_a_breast_cancer.pdf / 1 MB
-
- Score (nominal)
- 0
- Score source
- journalList
- Publication indicators
- PubMed ID
- 18588689 Opening in a new tab
- Uniform Resource Identifier
- https://opus.us.edu.pl/info/article/USL63e1a9242ba1442bbe48003bbe0242de/
- URN
urn:uni-kat-prod:USL63e1a9242ba1442bbe48003bbe0242de
* presented citation count is obtained through Internet information analysis, and it is close to the number calculated by the Publish or PerishOpening in a new tab system.