Polymorphisms in MMP9 and SIPA1 are associated with increased risk of nodal metastases in early-stage cervical cancer

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 were 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. Conflict of Interest Statement:The authors have no conflicts of interest to declare Article Precis: SNPs in MMP9 (rs17576) and SIAP1 (rs746429, rs931127) differ between cervical cancer patients with and without nodal metastases and after controlling for clinicopathologic factors.

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“…14,17,18 Mutations or abnormal expression of SIPA1 have been reported in hematopoietic malignancies and solid cancer in humans. 19 C57BL/6 mice were used as controls. CD45.1 B6.SJL-Ptprca Pepcb/BoyJ (Jackson Laboratory, Bar Harbor, ME) mice were used as recipients or donors for transplantations.…”

Suppression of SIPA-1 expression may reduce bladder cancer invasion and metastasis via the downregulation of E-cadherin and ZO-1

“…Recent studies have indicated that SIPA-1 is associated with the motility of cancer cells (14)(15)(16). In addition, nuclear SIPA-1 activates the integrin β1 promoter and promotes the invasion of breast cancer cells (15).…”

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