Interleukin-6 -634G>C genetic polymorphism is associated with prognosis following surgery for advanced thoracic esophageal squamous cell carcinoma.
OBJECTIVE
Systemic and/or local interleukin-6 (IL-6) reportedly plays an active role in the progression and prognosis of thoracic esophageal squamous cell carcinoma (TESCC). We assessed the associations between IL-6 and IL-6 receptor (IL-6R) genetic polymorphisms, tumoral IL-6 expression and survival rates following surgery.


METHODS
The study participants were 63 Japanese patients treated between 2003 and 2008 for T2-T4 advanced TESCC using curative esophagectomy without neoadjuvant treatment. We investigated IL-6 -634G>C (rs1800796) and IL-6R 48892A>C (rs8192284, Asp358Ala) genetic polymorphisms using DNA from peripheral blood samples. In addition, tumoral IL-6 expression was investigated immunohistochemically in resected specimens, and serum IL-6 was measured using a human IL-6 immunoassay.


RESULTS
There was a significant difference in survival between patients with the IL-6 -634G/G+G/C genotype and those with the C/C genotype, such that their 5-year overall survival rates were 42 and 72%, respectively. By contrast, the IL-6R 48892A /C genotype and tumoral IL-6 expression had no significant effect on survival among patients. Univariate and multivariate analyses revealed that IL-6 -634G>C polymorphism was an independent prognostic factor with a hazard ratio of 3.


CONCLUSIONS
IL-6 -634G>C genetic polymorphism may be a predictive prognostic factor in patients receiving esophagectomy for TESCC.
Department of Surgery, Akita University Graduate School of Medicine, Akita, Japan. motoyama@doc.med.akita-u.ac.jp
Satoru
S
Motoyama
Toshinobu
T
Nakatsu
Masatomo
M
Miura
Yudai
Y
Hinai
Yoshihiro
Y
Minamiya
Jun-ichi
J
Ogawa
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D016629:Esophagectomy; D005260:Female; D005838:Genotype; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D011379:Prognosis; D016016:Proportional Hazards Models; D019947:Receptors, Interleukin-6 / Q000235:genetics; D015996:Survival Rate
D015850:Interleukin-6; D019947:Receptors, Interleukin-6