Brooks Rebecca, Kizer Nora, Nguyen Loan, Jaishuen Atthapon, Wanat Karolyn, Nugent Elizabeth, Grigsby Perry, Allsworth Jenifer E, Rader Janet S
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.
Gynecol Oncol. 2010 Mar;116(3):539-43. doi: 10.1016/j.ygyno.2009.09.037. Epub 2009 Nov 10.
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.
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.
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.
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.
可遗传的多态性调节癌症转移效率。基质金属蛋白酶9（MMP9，rs17576）和信号转导和激活因子1（SIPA1，rs746429、rs931127）中的单核苷酸多态性（SNP）已与多种癌症的淋巴结转移相关。我们研究了这些SNP与早期宫颈癌淋巴结转移的相关性。
纳入连续接受盆腔淋巴结清扫术的IB期宫颈癌患者。将病例组（>1个阳性淋巴结，n = 101）与对照组（淋巴结病理阴性，n = 273）进行比较。使用TaqMan分析法对3个SNP的基因组DNA进行基因分型，并与临床变量进行关联分析。
SIPA1 rs931127位点的G等位基因与淋巴结疾病风险增加相关（比值比1.9，P = 0.03），SIPA1 rs746429位点接近显著相关（比值比2.2，P = 0.09），MMP9 rs17576位点相关（比值比1.5，P = 0.08）。在Ib1期病变患者（n = 304）中，SIPA1两个SNP位点的G等位基因均与淋巴结转移相关（rs746429比值比10.1，P = 0.01；rs931127比值比2.4，P = 0.01）。在无淋巴血管间隙浸润的患者中，SIPA1 SNP再次与淋巴结转移相关，所有淋巴结疾病患者在SIPA1 rs746429位点至少有一个G等位基因。
在这项病例对照研究中，在控制分期和淋巴血管间隙浸润后，SIPA1中的SNP在有或无淋巴结转移的宫颈癌患者以及MMP9中存在统计学差异。需要进一步研究来确定为转移级联提供许可背景的遗传多态性。
