Functional Polymorphisms in the Cyclooxygenase 2 (COX-2) Gene and Risk of Breast Cancer in a Chinese Population

Abstract

Cyclooxygenase (COX), the rate-limiting enzyme in prostaglandins (PG) synthesis, exists in at least two isoforms, COX-1 and COX-2. COX-2 plays an important role in carcinogenesis, and overexpression may increase proliferation, inhibit apoptosis, and enhance the invasiveness of breast cancer cells. Polymorphisms in the regulatory regions of the COX-2 gene may influence function and/or expression and contribute to interindividual variability in susceptibility to cancer. In this study three variants (−1195G/A and −765G/C in the promoter and 8473C/T in 3′UTR) of COX-2 were examined for correlation with breast cancer risk. A case-control study of 615 histologically confirmed breast cancer patients and 643 cancer-free controls frequency-matched for age were selected. Logistic regression analyses revealed that no overall significant associations were detected in the single-locus analysis between three polymorphisms of COX-2 and the risk of breast cancer. However, a significantly increased risk of breast cancer was associated with the combined genotypes containing “more than 3 variant alleles”' (adjusted OR = 1.37, 95% CI 1.01–1.84) compared with the combined genotypes with “0–3 variant alleles.” Haplotype analyses showed that haplotypes A−1195G−765T8473 and A−1195C−765T8473 were significantly associated with breast cancer risk (OR = 1.20, 95% CI 1.01–1.43 for A−1195G−765T8473; OR = 9.16, 95% CI 1.14–73.51 for A−1195C−765T8473) compared with the most common haplotype, G−1195G−765T8473. These findings indicate that these three variants in the regulatory regions of COX-2 may contribute to the etiology of breast cancer.