Abstract
Decoy Receptor 3 (DcR3), also called TNFRSF6β, is a member of the tumor necrosis factor receptor superfamily and is a soluble receptor for FasL. DcR3 is overexpressed in cancers and contributes to tumorigenesis through immune suppression and promotion of angiogenesis. We found that DcR3 is overexpressed in breast infiltrating ductal carcinoma (IDC) cells as compared with normal controls. We also conducted a case-control study analyzing associations of DcR3 polymorphisms with breast IDC risk. Subjects included 531 females with breast IDC and 592 age-matched healthy controls. Four DcR3 single nucleotide polymorphism loci with minor frequencies of more than 5% (rs3208008, rs41309931, rs2297441 and rs1291207) were genotyped using polymerase chain reaction restriction fragment length polymorphism and sequencing. Our results revealed significant differences in rs41309931genotypes and alleles (P < 0.01). Based on Haploview software analysis, the haplotype block Ars3208008 Grs41309931 Grs2297441 Ars1291207 exhibited the highest frequency, but, haplotype blocks Ars3208008 Trs41309931 Grs2297441 Ars1291207 and Crs3208008 Grs41309931 Grs2297441 Ars1291207 were associated with breast IDC risk. This study also detected associations between DcR3 gene polymorphisms and the clinicopathological features of breast IDC, including lymph node metastasis and C-erbB2, P53, estrogen receptor and progesterone receptor status. These data indicate that DcR3 gene polymorphisms are associated with sporadic breast IDC risk in Northeast Chinese females.
Highlights
Decoy Receptor 3 (DcR3), which maps to chromosomal region 20q13.3, is called tumor necrosis factor receptor super family member 6β (TNFRSF6β) and can bind FasL, LIGHT and TL1A [1, 2]
We found that DcR3 is overexpressed in breast infiltrating ductal carcinoma (IDC) cells as compared with normal controls
We found that the AGGG haplotype was associated with lymph node metastasis and may be important for breast IDC proximal and distal metastasis
Summary
Decoy Receptor 3 (DcR3), which maps to chromosomal region 20q13.3, is called tumor necrosis factor receptor super family member 6β (TNFRSF6β) and can bind FasL, LIGHT and TL1A [1, 2]. LIGHT, TL1A and their signal receptors are essential for promoting T cell proliferation, and DcR3-mediated blockade of these ligands was shown to reduce T cell activity [3, 4]. DcR3 can modulate activation and differentiation of dendritic cells [5] and macrophages [6, 7]. DcR3 expression is few detectable in normal tissues, but is upregulated in some malignant tissues [8,9,10,11]. DcR3 may be a potential prognostic indicator or marker for early tumor detection in certain kinds of cancer
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