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dc.contributor.authorHsieh, Szu-Min
dc.contributor.authorLook, Maxime
dc.contributor.authorSieuwerts, Anieta
dc.contributor.authorFoekens, John
dc.contributor.authorHunter, Kent
dc.date.accessioned2017-05-03T14:07:33Z
dc.date.available2017-05-03T14:07:33Z
dc.date.issued2009
dc.date.modified2010-09-15T07:04:47Z
dc.identifier.issn14655411
dc.identifier.doi10.1186/bcr2412
dc.identifier.urihttp://hdl.handle.net/10072/32983
dc.description.abstractIntroduction Previous studies in mouse models and pilot epidemiology studies have demonstrated that inherited polymorphisms are associated with inherited risk of tumor progression and poor outcome in human breast cancer. To extend these studies and gain better understanding of the function of inherited polymorphism in breast cancer progression, a validation prognosis study was performed in a large independent breast cancer patient population. Methods The study population consisted of 1863 Dutch patients with operable primary breast cancer from Rotterdam, The Netherlands. Genomic DNA was genotyped for the missense Pro436Leu RRP1B single nucleotide polymorphism (SNP) rs9306160 and the intronic SIPA1 SNP rs2448490 by SNP-specific PCR. Results A significant association of variants in RRP1B with metastasis-free survival was observed (P = 0.012), validating the role of RRP1B with inherited metastatic susceptibility. Stratification of patients revealed that association with patients' survival was found to be specifically restricted to estrogen receptor positive, lymph node-negative (ER+/LN-) patients (P = 0.011). The specific association with metastasis-free survival only in ER+/LN- patients was replicated for SIPA1, a second metastasis susceptibility gene known to physically interact with RRP1B (P = 0.006). Combining the genotypes of these two genes resulted in the significant ability to discriminate patients with poor metastasis-free survival (HR: 0.40, 95% CI: 0.24 to 0.68, P = 0.001). Conclusions These results validate SIPA1 and RRP1B as metastasis susceptibility genes and suggest that genotyping assays may be a useful supplement to other clinical and molecular indicators of prognosis. The results also suggest that lymphatic and hematogeneous metastases are genetically distinct that may involve different mechanisms. If true, these results suggest that metastatic disease, like primary breast cancer, may be multiple diseases and that stratification of late stage patients may therefore be required to fully understand breast cancer progression and metastasis.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.format.extent415462 bytes
dc.format.mimetypeapplication/pdf
dc.languageEnglish
dc.language.isoeng
dc.publisherBioMed Central
dc.publisher.placeUnited Kingdom
dc.relation.ispartofstudentpublicationY
dc.relation.ispartofpagefrom1
dc.relation.ispartofpageto9
dc.relation.ispartofissue5
dc.relation.ispartofjournalBreast Cancer Research
dc.relation.ispartofvolume11
dc.rights.retentionY
dc.subject.fieldofresearchCancer Genetics
dc.subject.fieldofresearchOncology and Carcinogenesis
dc.subject.fieldofresearchcode111203
dc.subject.fieldofresearchcode1112
dc.titleDistinct inherited metastasis susceptibility exists for different breast cancer subtypes: a prognosis study
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by/2.0
gro.rights.copyright© 2009 Hsieh et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
gro.date.issued2009
gro.hasfulltextFull Text
gro.griffith.authorLintell, Szu-Min K.


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