Document Detail

Genetic variation in CXCL12 and risk of cervical carcinoma: a population-based case-control study.
MedLine Citation:
PMID:  19788587     Owner:  NLM     Status:  MEDLINE    
CXCL12 provides a chemotactic signal-directing leucocyte migration and regulates metastatic behaviour of tumour cells. We conducted a population-based case-control study to test the hypothesis that common genetic variation in CXCL12 individual single nucleotide polymorphism (SNP) alleles and haplotypes] is associated with the risk of cervical carcinoma. Cases (n = 917) were residents of western Washington State diagnosed with invasive squamous cell cervical carcinoma (SCC), invasive adenocarcinoma or adenosquamous carcinoma, or adenocarcinoma in situ of the cervix. Control participants (n = 849) were identified from the source population by random digit telephone dialling 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% CI: 0.56-0.98). Among the ten common haplotypes inferred from the nine tagSNPs, one haplotype defined by minor alleles at 5'-flanking SNP rs17885289 and rs266085, and common alleles at the other seven SNPs occurred among 7.8% of cases and 10.6% of controls (dominant model OR = 0.72, 95% CI: 0.56-0.93; recessive model OR = 0.35, 95% CI: 0.12-0.97; and log-additive model OR = 0.72, 95% CI: 0.57-0.90). A stepwise procedure identified rs17885289, rs266085 and 3'-untranslated region (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 population-based studies are warranted to confirm these associations between genetic variation in CXCL12 and cervical cancer risk.
S N Maley; S M Schwartz; L G Johnson; M Malkki; Q Du; J R Daling; S S Li; L P Zhao; E W Petersdorf; M M Madeleine
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-09-24
Journal Detail:
Title:  International journal of immunogenetics     Volume:  36     ISSN:  1744-313X     ISO Abbreviation:  Int. J. Immunogenet.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-17     Completed Date:  2010-02-01     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  101232337     Medline TA:  Int J Immunogenet     Country:  England    
Other Details:
Languages:  eng     Pagination:  367-75     Citation Subset:  IM    
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MeSH Terms
3' Untranslated Regions
Carcinoma / diagnosis,  genetics*
Case-Control Studies
Chemokine CXCL12 / genetics*
Gene Expression Regulation, Neoplastic*
Genetic Variation*
Middle Aged
Neoplasm Invasiveness
Polymorphism, Single Nucleotide*
Uterine Cervical Neoplasms / diagnosis,  genetics*
Grant Support
N01-PC-35412/PC/NCI NIH HHS; P01 CA042792/CA/NCI NIH HHS; P01 CA042792-219003/CA/NCI NIH HHS; P01CA04279/CA/NCI NIH HHS; P30ES07033/ES/NIEHS NIH HHS; R01 CA112512/CA/NCI NIH HHS; R01 CA112512-01/CA/NCI NIH HHS; R01 CA112512-02/CA/NCI NIH HHS; R01 CA112512-03/CA/NCI NIH HHS; R01 CA112512-04/CA/NCI NIH HHS; R01 CA112512-05/CA/NCI NIH HHS; R01CA112512/CA/NCI NIH HHS; R25CA094880/CA/NCI NIH HHS; T32HG00035/HG/NHGRI NIH HHS
Reg. No./Substance:
0/3' Untranslated Regions; 0/CXCL12 protein, human; 0/Chemokine CXCL12

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