title: Association of cyclooxygenase 2 single-nucleotide polymorphisms and hepatocellular carcinoma in Taiwan.
abstract: Hepatocellular carcinoma (HCC) is a worldwide neoplasm for which early diagnosis is difficult and the prognosis is usually poor. Overexpression of cyclooxygenase 2 (COX-2) has been suggested to be associated with hepatocarcinogenesis. Although several COX-2 inhibitors have been used in hepatoma therapy, the genetic background between COX-2 and HCC remains largely unknown. In this study, the association of genotypic polymorphisms in COX-2 with HCC was investigated. 298 patients with HCC and 298 healthy controls recruited from the China Medical Hospital in Taiwan were genotyped by a PCR-RFLP method. We have investigated six polymorphic variants of COX-2, including A-1195G, G- 765C, T+8473C, and variants in introns 1, 5 and 6, and analyzed the association of specific genotype(s) with susceptibility to HCC. The results showed that, for each of the six genotypes, no differences un distribution between the HCC and control groups were found. There was neither obvious joint effect of COX-2 G-765C/intron 6 haplotype nor its genotypes with smoking or alcohol consumption on HCC risk. Environmental factors, other than smoking and alcohol drinking, may affect the post-natal expression of COX-2 in the etiology of HCC, which is an outcome of complex genetic and environmental interactions. Moreover , our immunohistochemistrical results indicated that the COX-2 protein was significantly over-expressed in well-differentiated HCC, but not significantly increased in expression in poorly-differentiated HCC. We suggest that COX-2 may be a determinant of the differentiation grade of HCC.
authors.affiliation: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, Republic of China.
authors.forename: Wen-Shin
authors.initials: WS
authors.lastname: Chang
authors.forename: Mei-Due
authors.initials: MD
authors.lastname: Yang
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Tsai
authors.forename: Li-Hao
authors.initials: LH
authors.lastname: Cheng
authors.forename: Long-Bin
authors.initials: LB
authors.lastname: Jeng
authors.forename: Woei-Chung
authors.initials: WC
authors.lastname: Lo
authors.forename: Chih-Hsueh
authors.initials: CH
authors.lastname: Lin
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
authors.forename: Da-Tian
authors.initials: DT
authors.lastname: Bau
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000235:genetics*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human