Functional polymorphisms in the cyclooxygenase 2 (COX-2) gene and risk of breast cancer in a Chinese population.
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.
Gao
Jun
J
Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
Ke
Qiao
Q
Ma
Hong-Xia
HX
Wang
Yan
Y
Zhou
Yan
Y
Hu
Zhi-Bin
ZB
Zhai
Xiang-Jun
XJ
Wang
Xue-Chen
XC
Qing
Jian-Wei
JW
Chen
Wen-Sen
WS
Jin
Guang-Fu
GF
Liu
Ji-Yong
JY
Tan
Yong-Fei
YF
Wang
Xin-Ru
XR
Shen
Hong-Bing
HB
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
D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human