Association of MCP‐1 promoter polymorphism with susceptibility to nasopharyngeal carcinoma

Abstract

Nasopharyngeal carcinoma (NPC) is prevalent among populations from southern China and is influenced by both genetic and environmental risk factors. The monocyte chemoattractant protein‐1 (MCP‐1), a member of cysteine‐cysteine chemokine family, plays critical roles in cancers. A polymorphism within the MCP‐1 promoter, rs1024611, has been shown to be significantly associated with the risk of several cancers. Our purpose was to assess the role of rs1024611 in NPC susceptibility. By polymerase chain reaction‐restriction fragment length polymorphism method, we genotyped rs1024611 in 593 patients with NPC (cases) and 480 cancer‐free subjects (controls) among Guangxi population from southern China. We observed that the G allele of rs1024611 was significantly associated with the increased risk of NPC in an additive model and dominant model, respectively (P = 0.018 and 0.010, odds ratio = 1.25 and 1.41, respectively). No appreciable variation of the effects was found across the subgroups stratified by age, sex, nationality, smoking and drinking status, and smoking level. In addition, significantly higher messenger RNA (mRNA) expression level of MCP‐1 was observed in NPC tissues than that in normal nasopharyngeal tissues, and the G allele of rs1024611 was significantly associated with elevated mRNA expression level of MCP‐1 in Epstein‐Barr virus‐transformed lymphocytes. In conclusion, our findings suggested that rs1024611 at the MCP‐1 promoter may be a risk factor for NPC. Further studies with larger sample size are necessary to confirm these findings.

Genome‐wide association study identifies 7q11.22 and 7q36.3 associated with noise‐induced hearing loss among Chinese population

“…We used data from the 1000 Genomic Projects as a reference data set for our imputation and generated genotypes of 3 830 431 SNPs in 298 individuals (Table ). Then, the genotype‐phenotype association analysis was performed by logistic regression model with the age and noise exposure time adjusted 22 . We drew a plot of Manhattan to show the association between genome‐wide SNPs and the risk of NIHL (Figure 2A).…”

“…Then, the genotype-phenotype association analysis was performed by logistic regression model with the age and noise exposure time adjusted. 22 We drew a plot of Manhattan to show the association between genome-wide SNPs and the risk of NIHL ( Figure 2A). The quantile-quantile plot shows a good match between the observed P-value distributions and the expected P-value distribution by chance (λ = 0.996; Figure 2B), which indicates that the overall inflation of genome-wide statistical results is minor at the discovery stage.…”

Current Status and Future Perspectives about Molecular Biomarkers of Nasopharyngeal Carcinoma

“…(a) NPC associated polymorphism and HLA With high throughput technologies, including whole-exome sequencing, wholegenome sequencing (WGS), and genome-wide association studies (GWAS), many SNPs associated with NPC risk or pathogenesis have been investigated. For example, polymorphism allele rs5275 in cyclooxygenase-2 (COX-2), rs1024611 in monocyte chemoattractant protein-1 (MCP-1), and rs3216733 in 78-kDa glucose-regulated protein (GRP78) gene promoter are associated with NPC susceptibility [21][22][23]. MCP-1 is a member of the chemokine family and acts as a potent chemoattractant for immune cells including memory T and lymphocytes.…”

“…Its association with NPC development via three distinct mechanisms has been proven. These mechanisms are: (i) facilitating tumour cell growth; (ii) modulating the tumour microenvironment (TME) by recruiting several immune cells; (iii) suppressing cytotoxic T-lymphocyte (CTLs) activities [ 22 ]. GRP78 encodes the HSPA78 protein (heat-shock 70-kDa protein 5), which is important for protein folding, where it promotes angiogenesis by upregulating vascular endothelial growth factor (VEGF) and facilitates tumour survival and proliferation [ 23 ].…”

Anticancer Potential of Raddeanin A, a Natural Triterpenoid Isolated from Anemone raddeana Regel

“…Breast cancer is a clinically complicated condition with a high incidence and mortality rate in developed countries [84][85][86][87][88]. According to the vicious cycle of bone metastasis, bone cells can interact with breast cancer cells in which tumor cells release pro-osteoclastic factors to induce osteoclastogenesis, while the bone matrix releases pro-tumorigenic growth factors.…”