CXCL12 G801A Polymorphism Is a Risk Factor for Sporadic Prostate Cancer Susceptibility

Abstract

Purpose: The chemokine CXCL12 and its receptor CXCR4 have been found to be associated with cancer metastasis. A single nucleotide polymorphism of CXCL12 G801A has been described and is regarded as a target for cis-acting factor that has the ability to up-regulate CXCL12 expression. Currently, there are no reports investigating the role of CXCL12 G801A polymorphism in prostate cancer (PC). Experimental Design: We genotyped CXCL12 G801A and p53Arg72Pro in 167 PC patients and 167 age-matched healthy subjects. Genotyping was done with PCR-RFLP and confirmed by direct DNA sequencing. To investigate the effect of the CXCL12 G801A polymorphism on CXCL12 and CXCR4 expression, immunohistochemistry was done in genotyped PC tissues. Results: A significant increase in the GA + AA genotype of the CXCL12 G801A polymorphism was observed in PC patients compared with healthy controls. The frequency of CXCL12 AA genotype was significantly higher in a group of patients with lymph node metastasis (23%) compared with those without metastasis (7 %). The frequency of CXCL12 expression in AA + GA genotype carriers was significantly higher than that in GG genotype carriers. Among the carriers with CXCL12 GA + AA genotypes, CXCR4 expression was also significantly higher compared with those with the GG genotype. Moreover, among the groups with both CXCL12-and CXCR4-positive staining, the frequency of the CXCL12 GA + AA genotype was high. Although we did not find a significant relationship between the frequency of the Arg/Pro + Pro/Pro genotype of p53 Arg72Pro and susceptibility in PC, there was a combined effect of CXCL12 GA + AA genotype and the p53 72Arg/Pro + Pro/Pro genotype on the frequency of PC. These results indicate that the p53 codon 72 polymorphism may interact with CXCL12 G801A. Conclusions: This is the first report showing that CXCL12 G801A polymorphism may be a risk factor for PC. Moreover, this study suggests that this polymorphism can be an important marker for detecting microinvasion and PC metastasis.

No Association between Common Chemokine and Chemokine Receptor Gene Variants and Prostate Cancer Risk

“…These include CC chemokine ligand 5 (CCL5, MIM#187011) À403 promoter variant (rs2107538G>A), CXC chemokine ligand 12 (CXCL12, MIM#600835) +180 3 ¶ untranslated regulatory variant (rs1801157G>A), CC chemokine receptor 2 (CCR2, MIM#601267) nonsynonymous variant CCR2V64I (rs1799864G>A), chemokine receptor 5 (CCR5, MIM#601373) 32 bp deletion variant CCR5D32, and CX3C chemokine receptor (CX3CR1, MIM#601470) nonsynonymous variants CX3CR1V249I (rs3732379G>A) and CX3CR1T280M (rs3732378C>T). The CXCL12 +801G>A polymorphism was recently shown to be a risk factor for prostate cancer in a Japanese study (13). The remaining variants, although associated with many infectious diseases and cancers, have not yet been investigated in prostate cancer.…”

Analysis of the stromal cell-derived factor 1-3'A gene polymorphism in pancreatic cancer

“…The most compelling evidence for the role of the SdF-1 G→a polymorphism in malignancy is provided by previous genotype and allele-frequency studies showing that this specific polymorphism is associated with a susceptibility to breast, lung and prostate cancer (36,38,(40)(41)(42). in the current study, we attempted to determine whether an association exists between this SdF-1 gene variant and pancreatic cancer.…”

“…on the other hand, current studies on colorectal cancer have failed to suggest a serious impact of the SdF-1 polymorphism on the risk of colorectal cancer development (43,44). Hypothetically, different mechanisms involved in the pathogenesis of colorectal carcinogenesis, along with a host of modifying molecular events, may account for this lack of association, in contrast to the documented role of the SdF-1 polymorphism in breast, lung, prostate and pancreatic cancer (36,38,(40)(41)(42). in other words, based on tissue origin, the influence of the sDF-1 gene polymorphism may contribute differentially between malignancies in mediating tumor progression, angiogenesis, metastasis and leukocyte migration.…”

“…This single nucleotide polymorphism of the SdF-1 gene has been investigated in type 1 diabetes and HiV-1 infection, and has been reported to be associated with an increased risk of non-Hodgkin's lymphoma in HiV-1 infected individuals (30,34,35). The SdF-1 G→a polymorphism has been investigated in various cancers, but no information is currently available regarding its role in pancreatic cancer (36)(37)(38)(39)(40)(41)(42)(43)(44).…”

Letter to the Editor Clarification of data for a meta-analysis: p53 codon 72 polymorphism and prostate cancer risk

“…Importantly, using the same search strategy and end-of-search date as those of Li et al (2011), we have located four relevant studies in Pubmed database with a total of 544 prostate cancer patients and 1005 controls (Wu et al, 1995;Hirata et al, 2007Hirata et al, , 2009Xu et al, 2010) (Table 1), which were not included in the meta-analysis even though they were consistent with the search criteria. Among them, two articles (Hirata et al, 2007(Hirata et al, , 2009 had duplicate data of cases and controls, so we selected the most complete and larger study (Hirata et al, 2007). Finally, three newly additional studies should be included.…”