Polymorphisms in MMP9 and SIPA1 are associated with increased risk of nodal metastases in early-stage cervical cancer.
OBJECTIVE
Heritable polymorphisms modulate metastatic efficiency in Cancer Single nucleotide polymorphisms (SNPs) in MMP9 (rs17576) and SIPA1 (rs746429, rs931127) have been associated with nodal metastases in multiple cancers. We investigated the association of these SNPs with nodal metastases in early-stage cervical cancer.


METHODS
Consecutive patients with stage IB cervical cancer who underwent a pelvic lymph node (LN) dissection were included. Cases (>1 positive LN, n=101) were compared with controls (negative LN pathology, n=273). Genotyping was performed on genomic DNA in the 3 SNPs using a TaqMan assay and correlated with clinical variables.


RESULTS
The G allele at SIPA1 rs931127 was associated with an increased risk of nodal disease (OR 1.9, P=0.03) and approached significance at SIPA 1 rs746429 (OR 2.2, P=0.09) and MMP9 rs17576 (OR 1.5, 0.08). In patients with stage Ib1 lesions (n=304), the G allele at both SIPA1 SNPs was associated with LN metastases (rs746429 OR 10.1, P=0.01; rs931127 OR 2.4, P=0.01). In patients with no lymph vascular space invasion, SIPA1 SNPs were again associated with LN metastases, and all patients with nodal disease had at least one G allele at SIPA1 rs746429.


CONCLUSIONS
In this case-control study, SNPs in SIPA1 varied statistically in cervical cancer patients with and without nodal metastases and in MMP9 after controlling for stage and lymphvascular space invasion. Further work is needed to characterize inherited polymorphisms that provide a permissive background for the metastatic cascade.
Brooks
Rebecca
R
Washington University School of Medicine/Barnes-Jewish Hospital, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, 4911 Barnes Jewish Hospital Plaza Box 8064, Saint Louis, MO 63110, USA. brooksr@wudosis.wustl.edu
Kizer
Nora
N
Nguyen
Loan
L
Jaishuen
Atthapon
A
Wanat
Karolyn
K
Nugent
Elizabeth
E
Grigsby
Perry
P
Allsworth
Jenifer E
JE
Rader
Janet S
JS
D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics*; D006801:Humans; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
D020690:GTPase-Activating Proteins; D009687:Nuclear Proteins; C490403:SIPA1 protein, human; D020780:Matrix Metalloproteinase 9