Genetic variation in CXCL12 and risk of cervical carcinoma: a population‐based case–control study

Abstract

SummaryCXCL12 provides a chemotactic signal directing leukocyte migration and regulates metastatic behavior of tumor cells. We conducted a population-based case-control study to test the hypothesis that common genetic variation in CXCL12 (single SNP alleles and haplotypes) is associated with the risk of cervical carcinoma. Cases (N=917) were women diagnosed with invasive squamous cell cervical carcinoma (SCC), adenocarcinoma or adenosquamous carcinoma or adenocarcinoma in situ (ACIS) of the cervix, while residents of western Washington State. Control participants (N=849) were identified from the source population by random digit telephone dialing and frequency matched to cases on county and age. Nine CXCL12 tagSNPs chosen from the SeattleSNPs database were genotyped. The minor allele of intronic SNP rs266085 was inversely associated with cervical cancer under a recessive genetic effects model (OR=0.74, 95% C.I. 0.56-0.98). Among the ten common haplotypes inferred from the 9 tagSNPs, one haplotype defined by minor alleles at 5' flanking SNP rs17885289 and rs266085, and common alleles at the other 7 SNPs occurred among 7.8% of cases and 10.6% of controls (dominant model OR=0.72, 95% C.I. 0.56-0.93; recessive model OR=0.35, 95% C.I. 0.12-0.97; and log additive model OR=0.72, 95% C.I. 0.57-0.90). A stepwise procedure identified rs17885289, rs266085, and 3' UTR SNP rs266093 as the most parsimonious subset of SNPs necessary to define the haplotype inversely associated with cervical cancer risk in our study. A 3' UTR SNP, rs1801157, previously found to be related to HIV pathogenesis, was not associated with cervical cancer risk. Further populationbased studies are warranted to confirm these associations between genetic variation in CXCL12 and cervical cancer risk.

Stromal cell-derived factor-1 G801A polymorphism and the risk factors for cervical cancer

“…In the present study, the SDF1-3' G801A SNP was not identified as a risk factor for cervical cancer. The present observations are in agreement with those by Maley et al (23) and Tee et al (24), which also observed no association between the SDF1-3' G801A polymorphism and risk of cervical cancer. However, in the present study, the P-value assessment of the trend observed for the SDF1-3' G801A polymorphism was on the borderline of statistical significance.…”

“…The possible role of the SDF1-3' A variant in the increased levels of transcription and protein has been reported (22). Certain studies have demonstrated no association between the SDF1-3' G801A single nucleotide polymorphism (SNP) and cervical carcinoma (23,24), however, the interaction between the SDF1-3' G801A SNP with other known risk factors of cervical cancer remain to be fully elucidated. In the present study, the SDF1-3' G801A genotype and allele frequencies were investigated in patients with cervical cancer (n=462) and healthy controls (n=497) in the Polish population, stratified based on contraceptive use, menopausal status, parity and history of tobacco smoking.…”

CXCL12 G801A polymorphism and cancer risk: An updated meta-analysis

“…Upon reviewing the abstracts, 10 articles were excluded since they were not case-control studies. After further examination of articles on full-text basis, 10 papers were excluded for P<0.05 in control HWE test [18][19][20][21] or failing to provide sufficient genotype data [22][23][24][25][26][27] . As a result, a total of 29 papers were included.…”

Stromal‐derived factor‐1 gene variations in pediatric patients with primary immune thrombocytopenia

“…Previous studies have shown single nucleotide polymorphisms (SNPs) in the human SDF-1 gene may influence SDF-1 function, such as serum SDF-1 level (11,12) and its expression in hematopoietic stem cells in peripheral blood (13,14). These SNPs have also shown to be associated with malignant diseases such as cervical cancer (15), in which SDF-1 was believed to affect the metastatic behavior of the cancer cell. In SLE (16), T-cell function and survival are suggested to be affected by SDF-1 polymorphism.…”