Prostaglandin-endoperoxide synthase 2 (PTGS2) gene polymorphisms and risk biliary tract cancer and gallstones:: a population-based study in Shanghai, China
Prostaglandin-endoperoxide synthase 2 (PTGS2) gene polymorphisms and risk biliary tract cancer and gallstones:: a population-based study in Shanghai, China
复制标题
DOI：
10.1093/carcin/bgi314
复制
发表时间：
2006-06-01
期刊：
影响因子：
4.7
通讯作者：
Hsing, Ann W.
中科院分区：
文献类型：
--
作者：
Sakoda, Lori C.;Gao, Yu-Tang;Hsing, Ann W.
有证据表明，慢性炎症易患胆道癌，使用非甾体类抗炎药（NSAID）具有保护作用。尽管NSAID降低癌症风险的机制尚不清楚，但NSAID通过阻断前列腺素内过氧化物合酶2（PTGS 2，通常称为考克斯-2）减少前列腺素的产生，PTGS 2是一种由促炎刺激诱导的酶，通常在恶性组织中过度表达。由于PTGS 2基因的变异体可以改变其编码酶的表达或功能，从而调节胆道的炎症反应，我们研究了8种PTGS 2多态性的相关性。（-645 C-> T; Ex3 - 8G-> C; IVS5 - 275 T-> G; IVS7 + 111 T-> C; Ex10 + 127 T-> C; Ex10 + 686 -> ATTAT -> TTATA; Ex10 + 837 T-> C; Ex 10 - 90 C-> T）与胆道癌和结石的患者进行了一项基于人群的病例对照研究。对411例胆道癌患者（胆囊癌237例，肝外胆管癌127例，壶腹癌47例）、895例胆系结石患者（胆囊癌673例，胆管癌222例）和786例健康人进行基因分型。仅在Ex 10 + 837 T-> C标记物和胆管癌风险之间观察到显著关联。相对于TT基因型个体，携带C等位基因（TC或CC基因型）的个体患胆管癌的风险为1.8倍（95%置信区间：1.2-2.7）。包括这种风险赋予等位基因的推断单倍型也与类似程度的胆管癌风险增加相关。我们的研究结果表明，一种常见的PTGS 2变异增加了胆管癌的风险。需要进一步的研究来证实和扩展我们在胆道癌研究中的发现，更全面地检查PTGS 2和其他炎症相关基因。
There is evidence that chronic inflammation predisposes to biliary tract cancer and that use of non-steroidal antiinflammatory drugs (NSAIDs) is protective. Although the mechanisms by which NSAIDs lower cancer risk remain unclear, NSAIDs reduce prostaglandin production by blocking prostaglandin-endoperoxide synthase 2 (PTGS2, commonly known as COX-2), an enzyme induced by proinflammatory stimuli that is often overexpressed in malignant tissue. Since variants in the PTGS2 gene may modify the expression or function of its encoded enzyme to modulate the inflammatory response in the biliary tract, we examined the associations of eight PTGS2 polymorphisms (-645C -> T; Ex3 -8G -> C; IVS5 -275T -> G; IVS7 + 111T -> C; Ex10 + 127T -> C; Ex10 + 686 -> ATTAT -> TTATA; Ex10 + 837T -> C; Ex10 -90C -> T) with biliary tract cancer and stones in a population-based case-control study conducted in Shanghai, China. Genotyping was performed for 411 patients with biliary tract cancer (237 gallbladder, 127 extrahepatic bile duct and 47 ampulla of Vater), 895 patients with biliary stones (673 gallbladder, 222 bile duct), and 786 healthy individuals randomly selected from the population. Significant associations were seen only between the Ex10 + 837T -> C marker and bile duct cancer risk. Relative to individuals with the TT genotype, those carrying the C allele (TC or CC genotype) had a 1.8-fold (95% confidence interval: 1.2-2.7) risk of bile duct cancer. Inferred haplotypes including this risk-conferring allele were also associated with increased bile duct cancer risk of similar magnitude. Our results suggest that a common PTGS2 variant increases bile duct cancer risk. Further investigation is needed to confirm and extend our findings in studies of biliary tract cancer that more comprehensively examine PTGS2 and other inflammation-related genes.