Aims: Cyclooxygenase-2 (COX-2) is involved in carcinogenesis, immune response suppression, apoptosis inhibition, angiogenesis, and tumour cell invasion and metastasis. The gene for COX-2, designated as PTGS2, carries several polymorphisms, such as -765G >C, 1195G/A in the promoter region, and 8473T >C in the 3' UTR, which have been associated with susceptibility to malignant disease. The aim of this study was to search for new mutations and polymorphisms in the COX-2 gene and to assess the relationship with breast cancer.
Materials and methods: In the present study, we identified a novel single nucleotide polymorphism, 169C >G, in exon 2 using polymerase chain reaction-single-strand conformation polymorphism analysis. This nucleotide change causes the amino acid change from proline to alanine at codon 57. To investigate the role of this polymorphism for breast cancer, we determined the prevalence of PTGS2 genotypes in 310 women with breast cancer and 310 gender- and age-matched healthy control subjects.
Results: Homozygous carriers of the 169-GG genotype were more frequent among patients (15.16%) than among controls (9.35%; P = 0.03). The odds ratio for carriers of this genotype for breast cancer was 1.76 (95% confidence interval, 1.20-3.05). Among patients, oestrogen receptor positivity was less frequent among carriers of a GG genotype (61.7%) than among carriers of a CC or GC genotype (72.3%; P = 0.02). Tumour size, histological grade, presence of primary lymph node metastases, progesterone receptor positivity, or age at diagnosis were not associated with PTGS2 genotypes.
Conclusion: We conclude that the homozygous PTGS2 169-GG genotype may be associated with breast cancer risk.