CXCL12 G801A polymorphism is a risk factor for sporadic prostate cancer susceptibility.
OBJECTIVE
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).


METHODS
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.
Hirata
Hiroshi
H
Department of Urology, San Francisco Veterans Affairs Medical Center and University of California, San Francisco, California 94121, USA.
Hinoda
Yuji
Y
Kikuno
Nobuyuki
N
Kawamoto
Ken
K
Dahiya
Angela V
AV
Suehiro
Yutaka
Y
Tanaka
Yuichiro
Y
Dahiya
Rajvir
R
D000368:Aged; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics*; D003062:Codon; D016158:Genes, p53; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors