Functional polymorphisms in the cyclooxygenase 2 (COX-2) gene and risk of breast cancer in a Chinese population

J Toxicol Environ Health A. 2007 Jun;70(11):908-15. doi: 10.1080/15287390701289966.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Membrane Proteins
  • Cyclooxygenase 2
  • PTGS2 protein, human