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

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

MASAHIKO KITO,¹ SATORU MOTOYAMA,^2,3 KAZUMA FUJITA,⁴ MASATOMO MIURA,⁴ HIROSHI NANJO,⁵ NAOKI SATO,¹ DAI SHIMIZU,¹ TOSHIHARU SATO,¹ KENICHI MAKINO,¹ TAE SUGAWARA,¹ AYA KATO,¹ DAISUKE TAMURA,¹ KAZUE TAKAHASHI,¹ YUKIYO KUMAZAWA,¹ WATARU SATO,¹ HIROSHI MIURA,¹ HIROMITSU SHIRASAWA,¹ AKIRA SATO,¹ JIN KUMAGAI¹ and YUKIHIRO TERADA¹

¹Department of Obstetrics and Gynecology, Akita University Graduate School of Medicine, Akita, Akita, Japan
²Department of Comprehensive Cancer Control, Akita University Graduate School of Medicine, Akita, Akita, Japan
³Division of Esophageal Surgery, Akita University Hospital, Akita, Akita, Japan
⁴Department of Pharmacy, Akita University Hospital, Akita, Akita, Japan
⁵Department of Pathology, Akita University Hospital, Akita, Akita, Japan

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.

keywords —— 1846C>T genetic polymorphism; C-reactive protein; endometrial cancer; lymph node metastasis; lymphovascular invasion

===============================

Tohoku J. Exp. Med., 2015, 237, 25-30

Correspondence: Masahiko Kito, M.D., Department of Obstetrics and Gynecology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, Akita 010-8543, Japan.

e-mail: kitom0103@yahoo.co.jp