Elsevier

Surgery

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

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

https://doi.org/10.1016/j.surg.2009.04.034Get rights and content

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.

Section snippets

Patients and methods

This study was approved by the Ethics Committee of Akita University School of Medicine. The study participants were 110 Japanese patients treated surgically without neoadjuvant therapy for thoracic esophageal cancer at Akita University Hospital between April 2003 and April 2008. Of the 110 patients, 33 received surgery consecutively between April 2007 and April 2008. The remaining 77 patients were selected at random for participation in the study from among those patients undergoing

Statistical analysis

Values are expressed as means ± standard deviations. Differences in genotype frequency were analyzed using the Pearson χ2 or Fisher exact tests of independence; the frequencies were evaluated to determine whether they were consistent with the expected Hardy-Weinberg proportions. Differences between groups were analyzed using the Student t test, Pearson χ2, or Fisher exact test. Relationships to infectious complications after esophagectomy were tested using univariate logistic regression

Results

The patient population included 96 males and 14 females with an average age of 64 ± 8 years (range, 38–82). Of the 110 lesions, 7 (6%) were located in the upper thoracic esophagus, 57 (52%) in the mid-thoracic segment, and 46 (42%) in the lower thoracic segment. For esophageal reconstruction, the gastric tube was used in 103 (94%) patients, pedicled colon in 6 patients, and pedicled jejunum in 1 patient. As a route of reconstruction, the posterior mediastinal route was used in 104 (95%)

Discussion

This study revealed that there is a significant correlation between the INF-γ 874A>T genetic polymorphism and infectious complications following esophagectomy in a cohort of patients with esophageal cancer. Adjusting for covariates, patients carrying the INF-γ 874A/T genotype appear to be more than 3.4 times as likely to develop a postoperative infection following esophagectomy than patients carrying the INF-γ 874A/A genotype. In contrast, there was no correlation between the other cytokine

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