A Case-Control Study of the Association Between the SPP1 Gene SNPs and the Susceptibility to Breast Cancer in Guangxi, China.

Lina Liang,Jiadong Liang,Limei Liang,Yibin Deng,Guijiang Wei,Yujin Tang,Guogang Pan,Jia Liu,Guanming Lu

doi:10.3389/fonc.2019.01415

Lina Liang, Jiadong Liang + Show 7 more

Open Access

https://doi.org/10.3389/fonc.2019.01415

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Abstract

Secreted phosphoprotein-1 (SPP1) has been reported to be involved in the pathogenesis of breast cancer (BRC), but the influence of SPP1 single nucleotide polymorphisms on the BRC susceptibility has been rarely reported. In this study, we explored the association between rs11730582, rs2853750, and rs35893069 in the SPP1 gene and the BRC susceptibility. We used Snapshot assay to detect SPP1 single nucleotide polymorphisms in 471 BRC patients and 471 controls. The plasma SPP1 level was measured by ELISA. We found that the CC genotype and C allele of rs11730582 were associated with a significantly decreased BRC risk compared with the TT genotype and T allele, respectively [CC vs. TT: odds ratio (OR) = 0.59, 95% CI = 0.37–0.94, P = 0.026; C vs. T: OR = 0.79, 95% CI = 0.65–0.96, P = 0.022]. In addition, BRC patients and controls with the rs11730582 CC genotype had a lower plasma SPP1 level than did BRC patients and controls with TT genotype (P = 0.007 and P = 0.011, respectively). Moreover, the proportions of rs11730582 CC genotype and C allele were decreased in BRC patients with clinical stages I–III compared with those with clinical stage IV (P = 0.012 and P = 0.003, respectively). Besides, the C-G-T haplotype was associated with a significantly decreased BRC risk compared with the T-A-T haplotype (OR = 0.69, 95% CI = 0.52–0.93, P = 0.015). However, there was no significant association between rs2853750 or rs35893069 and the BRC risk. In summary, our study found the association between rs11730582 and the risk of BRC and suggested that rs11730582 may promote the occurrence and development of BRC by regulating SPP1 expression.

Highlights

Breast cancer (BRC) is the most common cancer type and a leading cause of mortality among females in the world [1]
Logistic regression was used for exploring the association between Secreted phosphoprotein-1 (SPP1) single nucleotide polymorphisms (SNPs) and the susceptibility to breast cancer (BRC), and P values, odds ratio (OR), and 95% CI were adjusted by age at diagnosis and age at menarche
As for the distribution of age at diagnosis and age at menarche, there was no significant difference between BRC patients and the controls (P = 0.630 and P = 0.596, respectively)

Summary

INTRODUCTION

Breast cancer (BRC) is the most common cancer type and a leading cause of mortality among females in the world [1]. SPP1 was found to be increased in normal human breast tissue at a high risk of developing BRC [15] and promote inflammation and tumor growth by reprograming normal mammary fibroblasts [16]. Previous works had shown that single nucleotide polymorphisms (SNPs) in the SPP1 gene were associated with the risk or metastasis of some human cancers, such as oral carcinogenesis [17], hepatocellular carcinoma [18], and BRC [19]. The association between SNPs in the SPP1 gene and the susceptibility to BRC had been evaluated among the population in Egypt, but the sample size was small (60 cases and 60 controls) [20]. A further study with a larger sample size should be conducted immediately to reveal the association between SNPs in the SPP1 gene and the susceptibility to BRC. We genotyped SNPs in the SPP1 gene, measured its expression level, and assessed the impact of SNPs in the SPP1 gene on the expression level of SPP1 and other BRC-related characteristics

MATERIALS AND METHODS

RESULTS

DISCUSSION

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