Genetic association of deleted in colorectal carcinoma variants with breast cancer risk: A case-control study

Xinghan Liu,Kang Liu,Huafeng Kang,Zhijun Dai,Xijing Wang,Sidney W Fu,Haitao Guan,Shuqun Zhang,Xiaobin Ma,Yanjing Feng,Meng Wang,Cong Dai,Shuai Lin

doi:10.18632/oncotarget.9024

Abstract

Deleted in colorectal carcinoma (DCC), a netrin-1 dependence receptor, is correlated with cell progression, migration, and adhesion. Evidence indicated that DCC was frequently down-regulated in many cancers. However, the association of DCC with breast cancer remains uncertain. We conducted a case-control study to investigate the impact of three DCC gene variants (rs2229080, rs7504990, and rs4078288) on breast cancer susceptibility in Chinese women. This study included 560 breast cancer patients and 583 age-matched healthy controls from Northwest China. The three gene variants were genotyped via Sequenom MassARRAY. Odds ratios (ORs) and 95% confidence intervals (CIs) were utilized to evaluate the associations. We found that individuals with the rs2229080 C/G, C/C, and C/G-CC genotypes had a higher breast cancer risk, and the minor allele C was associated with increased breast cancer risk in an allele model. We observed a significantly decreased breast cancer risk with the rs7504990 C/T, T/T, and C/T-T/T genotypes, and the minor allele T was protective against breast cancer in an allele model. In addition, rs2229080 was associated with the axillary lymph node (LN) metastasis status. An age-stratified analysis revealed an association between rs2229080 and reduced breast cancer risk among older patients (≥ 49 years). Furthermore, the haplotype analysis showed that the Crs2229080Crs7504990Ars4078288 haplotype was associated with a decreased breast cancer risk. However, the results indicated a lack of association between rs4078288 and breast cancer risk. These findings affirmed that rs2229080 and rs7504990 polymorphisms in DCC might be related with breast cancer susceptibility in Chinese women.

Highlights

Breast cancer (BC) is the most common type of tumors in women worldwide, with 1.8 million incident cases and 464,000 death cases in 2013 [1]
Deleted in colorectal carcinoma (DCC) is a single-pass transmembrane protein that belongs to the immunoglobulin superfamily, and it is a candidate tumor suppressor gene located on chromosome 18q21 [14]
DCC extends more than 1.2 Mb with 29 exons [15], and is the largest tumor suppressor gene identified to date

Summary

Introduction

Breast cancer (BC) is the most common type of tumors in women worldwide, with 1.8 million incident cases and 464,000 death cases in 2013 [1]. A previous study estimated that the expression of axon guidance molecules (AGMs) was dysregulated during BC tumorigenesis and tumor progression, suggesting that AGMs might act as tumor suppressors and oncogene activators [3]. A family of extracellular proteins, are considered critical axon guidance cues for the positioning of axonal growth during neural circuit formation and various biological processes, including tumorigenesis, adhesion, and angiogenesis [5]. A complete loss of netrin-1 causes embryonic death and severe axon guidance defects www.impactjournals.com/oncotarget in mice [9]. Netrin-1 receptors such as DCC and SAX-3 (Robo) can function individually or in combination with other guidance receptors to control axon growth [10]. Evidence shows that DCC is widely expressed by neurons and is enriched at synapses to promote synaptogenesis between mammalian cortical neurons [11]. DCC can induce apoptosis in the absence of its ligand netrin-1 [12]

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