CRP 1846C>T Genetic Polymorphism Is Associated with Lymph Node Metastasis and/or Severe Lymphatic Invasion in Endometrial Cancer

Abstract

Endometrial cancer (EC) rates are rising in Japan. Lymph node (LN) metastasis is an important prognostic factor in EC, and its risk is increased with higher tumor grade, deep myometrial invasion, larger tumor size, and lymphovascular space invasion (LVSI). Current methodologies to assess these factors are unreliable. We previously showed the association between C-reactive protein (CRP) 1846C>T (rs1205) polymorphism and LN metastasis in esophageal, non-small cell lung, and breast cancers. The CRP gene is located on chromosome 1q21-q23, and the polymorphism in the noncoding region (1846C>T) of this gene decreases serum CRP levels. We investigated the relationship between CRP 1846C>T genetic polymorphism and LN metastasis or LVSI in 130 EC patients using polymerase chain reaction-restriction fragment length polymorphism. The CRP 1846C/T genotype was C/C in 11 patients, C/T in 58 patients and T/T in 61 patients. The patients were divided into two groups based on their CRP 1846 genotypes: "C/C" and "C/T + T/T". Nine (7%) and 18 (13%) patients, all with the polymorphism, had LN metastasis and moderate or prominent lymphatic invasion, respectively. LN metastasis and/or severe lymphatic invasion were observed in the C/T + T/T group, while patients with the C/C genotype had no LN metastases or severe lymphatic invasion. Univariate and multivariate logistic regression models revealed that the C/T + T/T patients had a significant likelihood of developing LN metastasis and/or severe lymphatic invasion. Our results suggest that CRP genetic polymorphism is a novel risk predictor of LN metastasis and/or lymphatic invasion in EC.

Clinicopathologic and prognostic significance of C-reactive protein/albumin ratio in patients with solid tumors: an updated systemic review and meta-analysis

“…With the presence of elevated serum CRP concentration, serum level of vascular endothelial growth factor is also increased, which plays a critical role in promoting cancer angiogenesis and improving oxygen supply of cancer cells [ 49 ]. Moreover, CRP genetic polymorphism was associated with lymph node (LN) metastasis in several cancer types, including ESCC, NSCLC, and breast cancer [ 50 ]. The CRP 1846C > T polymorphism could be a novel predictor of LN involvement in ESCC, which was more accurate than computed tomography [ 51 ].…”

C-reactive Protein as a Diagnostic and Prognostic Factor of Endometrial Cancer

“…Interestingly, measurement of CRP concentration is not only a prognostic indicator associated with C-reactive protein. Kito et al investigated the relationship between CRP 1846C>T genetic polymorphism and lymph node metastasis and lymphovascular space involve in 130 EC patients [27]. Among women with C/T or T/T polymorphism 7 % had lymph node metastasis and 6 % had moderate to prominent vascular invasion whilst none of the women with C/C genotype had such symptoms [27].…”

“…Kito et al investigated the relationship between CRP 1846C>T genetic polymorphism and lymph node metastasis and lymphovascular space involve in 130 EC patients [27]. Among women with C/T or T/T polymorphism 7 % had lymph node metastasis and 6 % had moderate to prominent vascular invasion whilst none of the women with C/C genotype had such symptoms [27]. Interestingly, plasma CRP concentration difference between these two groups was not statistically significant indicating that CRP gene polymorphism could be another independent prognosis predictor for patients with endometrial cancer.…”

Fibulin-4 is associated with prognosis of endometrial cancer patients and inhibits cancer cell invasion and metastasis via Wnt/β-catenin signaling pathway

“…Although early-stage endometrial cancer generally has a favorable outcome, up to 30% of endometrial cancer patients are diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage III or IV, and have a relatively poor prognosis, with local or extra-pelvic metastasis, and even distant metastasis [2, 3]. Metastasis causes most cancer deaths [4], so there is an urgent requirement for exploring the mechanism of tumor invasion and metastasis to further elucidate the progression of cancers.…”