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Association of death receptor 4 variant (683A>C) with ovarian cancer risk in BRCA1 mutation carriers

Dysregulation of apoptosis plays an important role in carcinogenesis. Therefore, apoptosis-associated genes like the death receptor 4 (DR4, TRAIL-R1) are interesting candidates for modifying the penetrance of breast and ovarian cancer in carriers of BRCA1 and BRCA2 mutations. The DR-4 haplotype 626C...

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Bibliographische Detailangaben
Hauptverfasser: Rath, Michèlle Geneviève (VerfasserIn) , Sutter, Christian (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 15 March 2012
In: International journal of cancer
Year: 2012, Jahrgang: 130, Heft: 6, Pages: 1314-1318
ISSN:1097-0215
DOI:10.1002/ijc.26134
Online-Zugang:Verlag, Volltext: http://dx.doi.org/10.1002/ijc.26134
Verlag, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/ijc.26134
Volltext
Verfasserangaben:Michelle G. Dick, Beatrix Versmold, Christoph Engel, Alfons Meindl, Norbert Arnold, Raymonda Varon‐Mateeva, Christian Sutter, Dieter Niederacher, Helmut Deissler, Sabine Preisler‐Adams, Karin Kast, Dieter Schäfer, Dorothea Gadzicki, Wolfram Heinritz, Barbara Wappenschmidt and Rita K. Schmutzler
Beschreibung
Zusammenfassung:Dysregulation of apoptosis plays an important role in carcinogenesis. Therefore, apoptosis-associated genes like the death receptor 4 (DR4, TRAIL-R1) are interesting candidates for modifying the penetrance of breast and ovarian cancer in carriers of BRCA1 and BRCA2 mutations. The DR-4 haplotype 626C-683C [626C>G, Thr209Arg (rs4871857) and 683A>C, Glu228Ala (rs17088993)] has recently been linked to an increased risk of breast cancer. To evaluate whether DR4 626C>G or DR4 683A>C modifies the risk of breast or ovarian cancer in carriers of BRCA1 and BRCA2 mutations, we undertook a national multicenter study including data of 840 carriers of breast cancer gene (BRCA) mutations. DNA samples were collected from 12 German research centers between 1996 and 2005 and were genotyped by the Taqman allelic discrimination assay. The association between genotypes and incidence of breast or ovarian cancer data was evaluated using a Cox proportional hazards regression model. We found evidence for a significant association of DR4 683A>C with a higher risk for ovarian cancer in carriers of BRCA1 mutations [n = 557, hazard ratio 1.78 (1.24-2.55), p = 0.009]. Our results thus indicate that the DR4 683A>C variant modifies the risk of ovarian cancer in carriers of BRCA1 mutations.
Beschreibung:First published: 11 April 2011
Gesehen am 17.12.2018
Beschreibung:Online Resource
ISSN:1097-0215
DOI:10.1002/ijc.26134

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