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In Reply:

Medizinische Poliklinik, Innenstadt, Klinikum der Universität München, München, Germany

Helga-Paula Török, Christian Folwaczny

Chirurgische Klinik und Poliklinik, Innenstadt and Medizinische Poliklinik, Innenstadt, Klinikum der Universität München, München, Germany

Agnes Schneider, Manfred Stolte

Institut für Pathologie, Klinikum Bayreuth, Bayreuth, Germany

Günter Brünnler, Ekehard D. Albert

Labor für Immungenetik, Kinderklinik und Kinderpoliklinik, Klinikum der Universität München, München, Germany

Reinhard Kopp

Chirurgische Klinik und Poliklinik, Grosshadern, Klinikum der Universität München, München, Germany

We welcome the comments by Drs Graziano and Ruzzo and appreciate their interest in our work. The frequency of the IL-1RN2/2 genotype in our study¹ exceeds previously reported percentages and we believe that this might reflect differences in the genetic background, which distinguishes early gastric cancer from advanced stages in which the percentages range between 10% and 20%.^2-6 Unfortunately, the frequencies of the IL-1RN genotypes were cited incorrectly by Graziano and Ruzzo, because percentages were used rather than the absolute numbers of patients. The correct frequencies, which are depicted in Table 3 of our article, are as follows: 51 of 88 patients for IL-1RN*2/2, eight of 88 patients for IL-1RN*1/2, and 27 of 88 patients for IL-1RN*1/1. Thus, in our trial, only the frequency of the genotype IL-1RN *2/2 was increased (58 v 8%) whereas the frequency of the homozygous genotype IL-1RN*1/1 was even decreased in early-stage gastric cancer (31% v 45%). The observed increase of the genotype IL-1RN*2/2 and the simultaneous decrease of the genotypes IL-1RN*1/1 and IL-1RN*1/2 parallels findings in articles on advanced-stage gastric cancer.^2-6

Cases with early-stage gastric cancer were selected retrospectively from the tumor bank of one institution led by a coauthor (M.S.), and comprise all accessible cases from 1993 to 2003. In addition, Drs Graziano and Ruzzo mentioned the difference in the average age between controls and patients. We certainly concede an age-dependent probability for the occurrence of gastric cancer. However, the difference between the incidences in both groups is too small to impact the conclusions of our study and similar age differences have also been reported in preceding trials.^3,4,6 We acknowledge that the unknown H pylori status of the blood donors might hamper the interpretation of our results. In previous studies,^2-6 various linkage disequilibria have been observed between the IL-1B and the IL-1RN loci. In our study, such a linkage disequilibrium was only observed in the subgroup with the intestinal type of early gastric cancer but not in the remainder of patients.

We certainly agree with Drs Graziano and Ruzzo that our data have to await confirmation and extension in independent trials, which should ideally compare early and advanced stages of gastric cancer in a prospective manner to avoid premature and exaggerated conclusions. In our opinion, this precaution is particularly relevant in genetic association studies.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Glas J, Török HP, Schneider A, et al: Allele 2 of the interleukin-1 receptor antagonist gene is associated with early gastric cancer. J Clin Oncol 22:4746-4752, 2004[Abstract/Free Full Text]

2. El-Omar EM, Carrington M, Chow WH, et al: Interleukin-1 polymorphisms associated with increased risk of gastric cancer. Nature 404:398-402, 2000[CrossRef][Medline]

3. Machado JC, Pharoah P, Sousa S, et al: Interleukin 1B and interleukin 1RN polymorphisms are associated with increased risk of gastric carcinoma. Gastroenterology 121:823-829, 2001[CrossRef][Medline]

4. Figueiredo C, Machado JC, Pharoah P, et al: Helicobacter pylori and interleukin 1 genotyping: An opportunity to identify high-risk individuals for gastric carcinoma. J Natl Cancer Inst 94:1680-1687, 2002[Abstract/Free Full Text]

5. El-Omar EM, Rabkin CS, Gammon MD, et al: Increased risk of noncardia gastric cancer associated with proinflammatory cytokine gene polymorphisms. Gastroenterology 124:1193-1201, 2003[CrossRef][Medline]

6. Machado JC, Figueiredo C, Canedo P, et al: A proinflammatory genetic profile increases the risk for chronic atrophic gastritis and gastric carcinoma. Gastroenterology 125:364-371, 2003[CrossRef][Medline]

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Related Correspondence

• Role of the Interleukin-1 Receptor Antagonist Gene Polymorphism (IL-1RN*2) in Early Gastric Cancer
  Francesco Graziano and Annamaria Ruzzo
  JCO 2005 23: 5272 [Full Text]

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