title: 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.affiliation: Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Gao
authors.forename: Qiao
authors.initials: Q
authors.lastname: Ke
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Ma
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Zhi-Bin
authors.initials: ZB
authors.lastname: Hu
authors.forename: Xiang-Jun
authors.initials: XJ
authors.lastname: Zhai
authors.forename: Xue-Chen
authors.initials: XC
authors.lastname: Wang
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Qing
authors.forename: Wen-Sen
authors.initials: WS
authors.lastname: Chen
authors.forename: Guang-Fu
authors.initials: GF
authors.lastname: Jin
authors.forename: Ji-Yong
authors.initials: JY
authors.lastname: Liu
authors.forename: Yong-Fei
authors.initials: YF
authors.lastname: Tan
authors.forename: Xin-Ru
authors.initials: XR
authors.lastname: Wang
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Shen
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D001943:Breast Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D002681:China / Q000453:epidemiology; D051546:Cyclooxygenase 2 / Q000235:genetics* / Q000378:metabolism; D016172:DNA Fingerprinting; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008593:Menopause; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human