Abstract
Duffy antigen receptor for chemokine (DARC) and CCBP2, the two members of chemokine decoy receptor family, restrain cell proliferation and invasion through sequestrating cytotoxic chemokines. Our previous research clarified two functional nonsynonymous single nucleotide polymorphisms (SNPs): rs12075 in DARC and rs2228468 in CCBP2 were significantly correlated with lymph node metastasis. However, the role of their genetic variations on survival of breast cancer remains unclear. In the present study, rs12075 in DARC and rs2228468 in CCBP2 were genotyped in 806 patients with primary breast cancer. The endpoint was recurrence‐free survival (RFS). Cox regression model was used to explore the association between SNPs and patients’ survival. The results revealed that participants with GG genotype in rs12075 appeared a higher recurrence risk compared with AG/AA genotype after adjustment with clinical parameters including lymph node status (AG+AA vs GG: hazard ratio [HR] = 0.54, 95% confidence interval [CI], 0.31‐0.93, P = 0.027). Furthermore, subgroup analysis revealed that GG genotype frequency of rs12075 had a positive correlation with RFS compared with AG/AA genotype (AG+AA vs GG: HR = 0.22, 95% CI, 0.05‐0.91, P = 0.021) in triple‐negative breast cancer (TNBC) subtype but not in other subtypes. No significant association between the genotypic variants and relapse risk was found in rs2228468 (AC+AA vs CC: HR = 0.80, 95% CI, 0.56‐1.14, P = 0.222). There was also no significant difference in survival among rs2228468 polymorphism in any subtypes. Our study suggested that rs12075 could be served as a key predictive factor of recurrence risk in breast cancer, especially for TNBC subtype. Further researches to monitor SNPs will provide further opportunities to determine clinical prognosis.
Highlights
Breast cancer, as the most prevalent diagnosed malignancy in female, is a heterogeneous multifactorial disease that attributes to complex interactions between genetic and environmental factors.[1,2] previous studies have identified women who carry a certain genetic variant response for its susceptibility in various populations, there remain a large proportion of treatment failure and mortality subsequently resulting from relapse and metastasis.[3]
Previous research in our laboratory has clarified the two nonsynonymous single nucleotide polymorphisms (SNPs): rs12075 (G42D) and rs2228468 (S373Y). rs12075 in Duffy antigen receptor for chemokine (DARC) and rs2228468 in CCBP2 were significantly correlated with lymph node metastasis in a dominant model, but not in a recessive model,[16] which manifested that genetic polymorphisms in the genes encoding Chemokine decoy receptors (CDR) could mediate metastatic risk
In view of the broad distribution of the two potentially functional nonsynonymous single nucleotide polymorphisms (SNPs) as well as the capability of decreasing the possibility of lymph node metastasis, we hypothesized that carrying different levels of CDR genetic variants and genotyping might affect the long‐term survival of breast cancer
Summary
As the most prevalent diagnosed malignancy in female, is a heterogeneous multifactorial disease that attributes to complex interactions between genetic and environmental factors.[1,2] previous studies have identified women who carry a certain genetic variant response for its susceptibility in various populations, there remain a large proportion of treatment failure and mortality subsequently resulting from relapse and metastasis.[3]. Chemokine and chemokine receptors are believed to promote tumor progression, stimulate angiogenesis, and induce epithelial‐mesenchymal transition.[4,5,6,7] Emerging evidence indicates Rs12075 in DARC and rs2228468 in CCBP2 were significantly correlated with lymph node metastasis in a dominant model, but not in a recessive model,[16] which manifested that genetic polymorphisms in the genes encoding CDRs could mediate metastatic risk. In view of the broad distribution of the two potentially functional nonsynonymous single nucleotide polymorphisms (SNPs) as well as the capability of decreasing the possibility of lymph node metastasis, we hypothesized that carrying different levels of CDR genetic variants and genotyping might affect the long‐term survival of breast cancer. Our research attempted to seek a promising recurrence predictor which could optimize more appropriate therapeutic measures
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