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

• Published in: Clinical cancer research Vol. 13; no. 17; pp. 5056 - 5062
• Main Authors: HIRATA, Hiroshi, HINODA, Yuji, KIKUNO, Nobuyuki, KAWAMOTO, Ken, DAHIYA, Angela V, SUEHIRO, Yutaka, TANAKA, Yuichiro, DAHIYA, Rajvir
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.09.2007
• Subjects: Aged; Antineoplastic agents; Biological and medical sciences; Chemokine CXCL12; Chemokines, CXC - genetics; Codon; CXCL12; CXCR4; Genes, p53; Genetic Predisposition to Disease; Genotype; Gynecology. Andrology. Obstetrics; Humans; IHC; Lymphatic Metastasis; Male; Male genital diseases; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; p53; PCR-RFLP; Pharmacology. Drug treatments; Polymorphism; Polymorphism, Genetic; Polymorphism, Single Nucleotide; prostate cancer; Prostatic Neoplasms - etiology; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Risk Factors; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Urinary system disease; Genetic variability; Prostate disease; Sporadic; Genotype; Malignant tumor; Epidemiology; stromal-derived factor-1α; Stromal cell derived factor 1; Risk factor; Male genital diseases; Prostate cancer; Polymorphism
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-07-0859

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.