Allellic variants in regulatory regions of cyclooxygenase-2: association with advanced colorectal adenoma.
Allellic variants in regulatory regions of cyclooxygenase-2: association with advanced colorectal adenoma.
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DOI：
10.1038/sj.bjc.6602806
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发表时间：
2005-10-17
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
Cyclooxygenase 2 (Cox-2) is upregulated in colorectal adenomas and carcinomas. Polymorphisms in the Cox-2 gene may influence its function and/or its expression and may modify the protective effect of nonsteroidal anti-inflammatory drugs (NSAIDs), thereby impacting individuals' risk of developing colorectal cancer and response to prevention/intervention strategies. In a nested case–control study, four polymorphisms in the Cox-2 gene (two in the promoter, −663 insertion/deletion, GT/(GT) and −798 A/G; one in intron 5-5229, T/G; one in 3′untranslated region (UTR)-8494, T/C) were genotyped in 726 cases of colorectal adenomas and 729 age- and gender-matched controls in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial. There was no significant association between the Cox-2 polymorphisms and adenoma development in the overall population. However, in males, the relatively rare heterozygous genotype GT/(GT) at −663 in the promoter and the variant homozygous genotype G/G at intron 5-5229 appeared to have inverse associations (odds ratio (OR)=0.59, confidence interval (CI): 0.34–1.02 and OR=0.48, CI: 0.24–0.99, respectively), whereas the heterozygous genotype T/C at 3′UTR-8494 had a positive association (OR=1.31, CI: 1.01–1.71) with adenoma development. Furthermore, the haplotype carrying the risk-conferring 3′UTR-8494 variant was associated with a 35% increase in the odds for adenoma incidence in males (OR=1.35, CI: 1.07–1.70), but the one with a risk allele at 3′UTR-8494 and a protective allele at intron 5-5229 had no effect on adenoma development (OR=0.85, CI: 0.66–1.09). Gender-related differences in adenoma risk were also noted with tobacco usage and protective effects of NSAIDs. Our analysis underscores the significance of the overall allelic architecture of Cox-2 as an important determinant for risk assessment.
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影响因子：
158.5
作者：
GIOVANNUCCI, E;EGAN, KM;SPEIZER, FE
通讯作者：
SPEIZER, FE
DOI：
10.1016/s0197-2456(00)00097-0
发表时间：
2000-12-01
期刊：
CONTROLLED CLINICAL TRIALS
影响因子：
--
作者：
Gohagan, JK;Prorok, PC;Kramer, BS
通讯作者：
Kramer, BS
影响因子：
4.8
作者：
Dixon, DA;Kaplan, CD;Prescott, SM
通讯作者：
Prescott, SM
影响因子：
9.8
作者：
McCashland, TM;Brand, R;de Garmo, P
通讯作者：
de Garmo, P
影响因子：
3.5
作者：
Mestre, JR;Rivadeneira, DE;Daly, JM
通讯作者：
Daly, JM