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.

• Authors: Jun Gao, Qiao Ke, Hong-Xia Ma, Yan Wang, Yan Zhou, Zhi-Bin Hu, Xiang-Jun Zhai, Xue-Chen Wang, Jian-Wei Qing, Wen-Sen Chen, Guang-Fu Jin, Ji-Yong Liu, Yong-Fei Tan, Xin-Ru Wang, Hong-Bing Shen
• Journal: Journal of toxicology and environmental health. Part A (J Toxicol Environ Health A) Vol. 70 Issue 11 Pg. 908-15 (Jun 2007) ISSN: 1528-7394 [Print] England
• PMID: 17479405 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Membrane Proteins
• Cyclooxygenase 2
• PTGS2 protein, human

Topics

• Adenocarcinoma (enzymology, epidemiology, genetics)
• Asian People (genetics)
• Breast Neoplasms (enzymology, epidemiology, genetics)
• China (epidemiology)
• Cyclooxygenase 2 (genetics, metabolism)
• DNA Fingerprinting
• Female
• Genetic Predisposition to Disease
• Genotype
• Humans
• Logistic Models
• Membrane Proteins (genetics, metabolism)
• Menopause
• Middle Aged
• Polymorphism, Single Nucleotide
• Risk Factors