Genetic variation in CXCL12 and risk of cervical carcinoma: a population-based case-control study.
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.
Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
S N
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Maley
S M
SM
Schwartz
L G
LG
Johnson
M
M
Malkki
Q
Q
Du
J R
JR
Daling
S S
SS
Li
L P
LP
Zhao
E W
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Petersdorf
M M
MM
Madeleine
D020413:3' Untranslated Regions; D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002277:Carcinoma / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D054377:Chemokine CXCL12 / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D020641:Polymorphism, Single Nucleotide; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000235:genetics*
D020413:3' Untranslated Regions; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12