Interferon-gamma 874A>T genetic polymorphism is associated with infectious complications following surgery in patients with thoracic esophageal cancer

Motoyama, Satoru; Miura, Masatomo; Hinai, Yudai; Maruyama, Kiyotomi; Usami, Shuetsu; Nakatsu, Toshinobu; Saito, Hajime; Minamiya, Yoshihiro; Murata, Katsuyuki; Suzuki, Toshio; Ogawa, Jun-ichi

doi:10.1016/j.surg.2009.04.034

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Volume 146, Issue 5 , Pages 931-938, November 2009

Interferon-gamma 874A>T genetic polymorphism is associated with infectious complications following surgery in patients with thoracic esophageal cancer

Satoru Motoyama, MD, PhD
- Department of Surgery, Akita University School of Medicine, Akita, Japan
- Reprint requests: Satoru Motoyama, MD, PhD, Department of Surgery, Akita University School of Medicine, 1-1-1 Hondo, Akita, Japan 010-8543.
Masatomo Miura, PhD
- Department of Pharmacy, Akita University Hospital, Akita, Japan
Yudai Hinai, PhD
- Department of Pharmacy, Akita University Hospital, Akita, Japan
Kiyotomi Maruyama, MD, PhD
- Department of Surgery, Akita University School of Medicine, Akita, Japan
Shuetsu Usami, MD
- Department of Surgery, Akita University School of Medicine, Akita, Japan
Toshinobu Nakatsu, MD
- Department of Surgery, Akita University School of Medicine, Akita, Japan
Hajime Saito, MD, PhD
- Department of Surgery, Akita University School of Medicine, Akita, Japan
Yoshihiro Minamiya, MD, PhD
- Department of Surgery, Akita University School of Medicine, Akita, Japan
Katsuyuki Murata, MD, PhD
- Department of Environmental Health Sciences, Akita University School of Medicine, Akita, Japan
Toshio Suzuki, PhD
- Department of Pharmacy, Akita University Hospital, Akita, Japan
Jun-ichi Ogawa, MD, PhD
- Department of Surgery, Akita University School of Medicine, Akita, Japan

Accepted 17 April 2009. published online 07 September 2009.

Background

Cytokines play a major role in the organization of orchestrated responses to infections, and there is an emerging consensus that cytokine gene polymorphisms mediate individual variations in cytokine expression. Our aim in this study was to assess whether cytokine polymorphisms were associated with infectious complications following esophagectomy in a Japanese population.

Methods

The study participants were Japanese patients treated with transthoracic esophagectomy without neoadjuvant treatment. DNA was extracted from blood samples, and genetic polymorphisms for interferon (INF)-γ, tumor necrosis factor-α and -β, transforming growth factor-β1, interleukin (IL)-1β, IL-1 receptor antagonist, IL-2, IL-6, IL-6 receptor, IL-10, and IL-12β were investigated using the polymerase chain reaction-restriction fragment length polymorphism method. We then assessed the association between gene polymorphisms and postoperative infection.

Results

Of the 110 patients studied, 18 (16%) developed a postoperative infection (pneumonia, 14 patients; pyothorax, 5; intraabdominal abscess, 1; neck abscess, 1; sepsis, 2). Although the characteristics of patients who developed postoperative infections did not differ, analysis of the genotypes using the Fisher exact test revealed a significantly (P = .0215) greater incidence of postoperative infections among those carrying the INF-γ 874 (rs2430561) A/A and A/T genotypes. Moreover, univariate and multivariate logistic regression models showed patients carrying the INF-γ 874A/T genotype were significantly more likely to develop postoperative infectious complications (odds ratio>3.4).

Conclusion

Our findings suggest that the IFN-γ 874A>T polymorphism is potentially predictive of the likelihood that patients undergoing esophagectomy for thoracic esophageal cancer will develop postoperative infections. This polymorphism may therefore have important clinical relevance and should be considered when treatment regimens are designed.