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Dick, Michelle G.; Versmold, Beatrix; Engel, Christoph; Meindl, Alfons; Arnold, Norbert; Varon‐Mateeva, Raymonda; Sutter, Christian; Niederacher, Dieter; Deissler, Helmut; Preisler‐Adams, Sabine; Kast, Karin; Schäfer, Dieter; Gadzicki, Dorothea; Heinritz, Wolfram; Wappenschmidt, Barbara; Schmutzler, Rita K.

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

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  • Medientyp: E-Artikel
  • Titel: Association of death receptor 4 variant (683AC) with ovarian cancer risk in BRCA1 mutation carriers
  • Beteiligte: Dick, Michelle G.; Versmold, Beatrix; Engel, Christoph; Meindl, Alfons; Arnold, Norbert; Varon‐Mateeva, Raymonda; Sutter, Christian; Niederacher, Dieter; Deissler, Helmut; Preisler‐Adams, Sabine; Kast, Karin; Schäfer, Dieter; Gadzicki, Dorothea; Heinritz, Wolfram; Wappenschmidt, Barbara; Schmutzler, Rita K.
  • Erschienen: Wiley, 2012
  • Erschienen in: International Journal of Cancer
  • Sprache: Englisch
  • DOI: 10.1002/ijc.26134
  • ISSN: 0020-7136; 1097-0215
  • Schlagwörter: Cancer Research ; Oncology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Dysregulation of apoptosis plays an important role in carcinogenesis. Therefore, apoptosis‐associated genes like the <jats:italic>death receptor 4</jats:italic> (<jats:italic>DR4, TRAIL‐R1</jats:italic>) are interesting candidates for modifying the penetrance of breast and ovarian cancer in carriers of <jats:italic>BRCA1</jats:italic> and <jats:italic>BRCA2</jats:italic> mutations. The <jats:italic>DR‐4</jats:italic> haplotype 626C–683C [626C&gt;G, Thr209Arg (rs4871857) and 683A&gt;C, Glu228Ala (rs17088993)] has recently been linked to an increased risk of breast cancer. To evaluate whether <jats:italic>DR4</jats:italic> 626C&gt;G or <jats:italic>DR4</jats:italic> 683A&gt;C modifies the risk of breast or ovarian cancer in carriers of <jats:italic>BRCA1</jats:italic> and <jats:italic>BRCA2</jats:italic> 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 <jats:italic>DR4</jats:italic> 683A&gt;C with a higher risk for ovarian cancer in carriers of <jats:italic>BRCA1</jats:italic> mutations [<jats:italic>n</jats:italic> = 557, hazard ratio 1.78 (1.24–2.55), <jats:italic>p</jats:italic> = 0.009]. Our results thus indicate that the <jats:italic>DR4</jats:italic> 683A&gt;C variant modifies the risk of ovarian cancer in carriers of BRCA1 mutations.</jats:p>
  • Zugangsstatus: Freier Zugang