CRP genetic polymorphism is associated with lymph node metastasis in thoracic esophageal squamous cell cancer.
BACKGROUND
Lymph node involvement is the most important prognostic factor in thoracic esophageal cancer. A more accurate molecular technique for diagnosing lymph node metastasis and a better understanding of the molecular mechanisms governing lymph node metastasis would be highly desirable. The purpose of this study is to examine the association between inflammation-related genetic polymorphisms and lymph node metastasis.


METHODS
The study participants were 113 Japanese patients undergoing curative surgery for thoracic esophageal squamous cell cancer. DNA was extracted from blood samples and genetic polymorphisms in C-reactive protein (CRP), tumor necrosis factor (TNF)-alpha and -beta, interferon (IFN)-gamma, transforming growth factor (TGF)- beta, interleukin (IL)-1beta, IL-1 receptor antagonist, IL-2, IL-4, IL-6, IL-6 receptor, IL-10, and IL-12beta were investigated using the polymerase chain reaction-restriction fragment length polymorphism method. We then assessed the association between inflammation-related genes and lymph node metastasis.


RESULTS
For CRP 1846C>T polymorphism, the frequency of the 1846T/T genotype was significantly higher in patients with lymph node metastasis (P = 0.0043), and the odds ratio (3.040) derived from logistic regression models indicated that the 1846T/T genotype significantly increases the likelihood of lymph node metastasis. In submucosal cancer, the utility of CRP 1846C>T polymorphism for predicting lymph node involvement was superior to usual methods (computed tomography and ultrasonography), with positive and negative predictive values of 69% and 75%, respectively.


CONCLUSIONS
These findings suggest that CRP polymorphism is a potentially effective predictor of lymph node metastasis and may thus be useful for deciding on treatment strategy.
Motoyama
Satoru
S
Department of Surgery, Akita University School of Medicine, Akita, Japan. motoyama@doc.med.akita-u.ac.jp
Miura
Masatomo
M
Hinai
Yudai
Y
Maruyama
Kiyotomi
K
Usami
Shuetsu
S
Saito
Hajime
H
Minamiya
Yoshihiro
Y
Satoh
Shigeru
S
Murata
Katsuyuki
K
Suzuki
Toshio
T
Ogawa
Jun-ichi
J
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002097:C-Reactive Protein / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000556:secondary; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D008198:Lymph Nodes / Q000473:pathology* / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D053701:Receptors, Interleukin-10 / Q000235:genetics; D019947:Receptors, Interleukin-6 / Q000235:genetics; D015996:Survival Rate; D013899:Thoracic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D014408:Biomarkers, Tumor; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D053701:Receptors, Interleukin-10; D019947:Receptors, Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4; D002097:C-Reactive Protein