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.

This work was supported in part by the National Key Basic Research Program Grants (2002CB512908), Jiangsu Natural Science Foundation (BK2004145), and Postdoctoral Science Foundation of China (2004035218).