ONCOmmunity

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

By: Dick MG, Versmold B, Engel C, Meindl A, Arnold N, Varon-Mateeva R, Sutter C, Niederacher D, Deissler H, Preisler-Adams S, Kast K, Schäfer D, Gadzicki D, Heinritz W, Wappenschmidt B, Schmutzler RK.

Center Familial Breast and Ovarian Cancer, Department of Gynecology and Obstetrics and Center for Integrated Oncology (CIO), University Cologne, Germany.
Int J Cancer. 2011 Apr 11. doi: 10.1002/ijc.26134.

Abstract

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 the BRCA1 and BRCA2 mutations. The DR-4 haplotyp 626C-683C (626C>G, Thr209Arg (rs4871857) and 683A>C, Glu228Ala (rs17088993)) has recently been linked to an increased risk of breast cancer. In order to evaluate whether DR4 626C>G or DR4 683A>C modifies the risk of breast or ovarian cancer in BRCA1 and BRCA2 mutation carriers, we undertook a national multi-center study including data of 840 BRCA mutation carriers. 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, HR 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 BRCA1 mutation carriers.

PMID: 21484799 [PubMed - as supplied by publisher] Source: National Library of Medicine.