1. ¹Department of Pathology, University Medical Centre, Utrecht, The Netherlands
2. ²Department of Human Anatomy, Medical University of Lublin, Lublin, Poland
3. ³Department of Pathology, Academic Medical Centre, Amsterdam, The Netherlands
4. ⁴Department of Endocrinology, Academic Medical Centre, Amsterdam, The Netherlands

Correspondence: Dr AN Milne, MD, PhD, Department of Pathology, H04-312, University Medical Center Utrecht, Heidelberglaan 100, Postbox 85500, Utrecht 3508 GA, The Netherlands. E-mail: a.n.a.milne@umcutrecht.nl

Received 7 May 2007; Revised 10 September 2007; Accepted 19 September 2007; Published online 29 February 2008.

Abstract

COX-2 overexpression is known to be an important mechanism in gastric carcinogenesis. Previously we have found that early-onset gastric cancer has a unique COX-2 low-expressing phenotype that differs significantly from that of the frequent overexpression seen in conventional gastric cancers. To investigate whether the COX-2 –765 G>C promoter polymorphism (known to lead to a reduction of COX-2 promoter activity in the colon) may explain this difference in expression, we carried out single-nucleotide polymorphism (SNP) analysis of 241 gastric cancers, including early-onset gastric cancer, conventional gastric cancers and gastric stump cancers, as well as in 100 control patients, using real-time PCR and sequence analysis, and correlated these findings with COX-2 expression using immunohistochemistry. We found that the C allele was present in 30% of early-onset gastric cancers, 24% of conventional gastric cancer, 23% of stump cancers, in contrast to 41% in the control group. There was a statistically significant difference in the presence of the C allele in patients with gastric cancer compared with the control group (P=0.007), with the C allele being associated with protection against gastric cancer. However, there was no significant difference between the early-onset, conventional and stump gastric cancer groups. Interestingly, there was no correlation between the presence of the C allele and a difference in COX-2 expression. In summary, we show that the COX-2 –765 G allele promoter polymorphism is significantly associated with gastric cancer when compared with the normal control group, but does not appear to be related directly to COX-2 expression pattern in gastric cancer. Although early-onset gastric cancers appear to have a unique COX-2 expression pattern when compared with conventional gastric cancer, the exact mechanism by which this occurs is yet to be elucidated.