Faculty Collaboration Database

Polymorphisms in MMP9 and SIPA1 are associated with increased risk of nodal metastases in early-stage cervical cancer. Gynecol Oncol 2010 Mar;116(3):539-43

Date

11/13/2009

Pubmed ID

19906411

Pubmed Central ID

PMC2822070

DOI

10.1016/j.ygyno.2009.09.037

Scopus ID

2-s2.0-75749152523 (requires institutional sign-in at Scopus site)   34 Citations

Abstract

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.

Author List

Brooks R, Kizer N, Nguyen L, Jaishuen A, Wanat K, Nugent E, Grigsby P, Allsworth JE, Rader JS

Authors

Janet Sue Rader MD Chair, Professor in the Obstetrics and Gynecology department at Medical College of Wisconsin
Karolyn A. Wanat MD Chair, Professor in the Dermatology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Alleles
Case-Control Studies
Female
GTPase-Activating Proteins
Humans
Lymphatic Metastasis
Lymphatic Vessels
Matrix Metalloproteinase 9
Neoplasm Staging
Nuclear Proteins
Polymorphism, Single Nucleotide
Uterine Cervical Neoplasms