Statin use, candidate mevalonate pathway biomarkers, and colon cancer survival in a population-based cohort study.
Statin use, candidate mevalonate pathway biomarkers, and colon cancer survival in a population-based cohort study.
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在一项基于人群的队列研究中，他汀类药物的使用，候选甲酸盐途径生物标志物和结肠癌存活。
DOI：
10.1038/bjc.2017.139
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发表时间：
2017-06-06
影响因子：
8.8
通讯作者：
Coleman HG
中科院分区：
文献类型：
--
作者：
Gray RT;Loughrey MB;Bankhead P;Cardwell CR;McQuaid S;O'Neill RF;Arthur K;Bingham V;McGready C;Gavin AT;James JA;Hamilton PW;Salto-Tellez M;Murray LJ;Coleman HG
结直肠癌诊断后使用他汀类药物可能会改善生存率，但观察性研究的证据相互矛盾。他汀类药物的抗癌作用可能仅限于某些分子亚组。在这项基于人群的队列研究中，评估了p53和3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）表达、KRAS突变之间的相互作用，以及他汀类药物使用与结肠癌生存率之间的相关性。该队列由2004年至2008年诊断的740名II期和III期结肠癌患者组成。通过临床记录审查确定他汀类药物的使用。取出组织块以确定组织微阵列中p53和HMGCR的免疫组织化学表达以及提取的DNA中KRAS突变的存在。使用考克斯比例风险模型计算结直肠癌特异性生存期和总生存期的风险比（HR）和95%置信区间（CI）。在该队列中，他汀类药物的使用与癌症特异性生存率的改善无关（HR=0.91，95% CI 0.64-1.28）。当分析按肿瘤p53分层时，他汀类药物的使用也与生存率的改善无关。（野生型HR=1.31，95% CI 0.67-2.56 vs异常HR=0.80，95% CI 0.52-1.24），HMGCR（HMGCR-高HR=0.69，95% CI 0.40-1.18 vs HMGCR-低HR=1.10，95% CI 0.66-1.84）和KRAS（野生型HR=0.73，95% CI 0.44-1.19 vs突变型HR=1.21，95% CI 0.70-2.21）状态。在这个基于人群的结肠癌患者队列中，他汀类药物的使用与生存率的改善无关，无论是独立的还是按潜在的甲羟戊酸途径生物标志物分层的。
Statin use after colorectal cancer diagnosis may improve survival but evidence from observational studies is conflicting. The anti-cancer effect of statins may be restricted to certain molecular subgroups. In this population-based cohort study, the interaction between p53 and 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGCR) expression, KRAS mutations, and the association between statin use and colon cancer survival was assessed. The cohort consisted of 740 stage II and III colon cancer patients diagnosed between 2004 and 2008. Statin use was determined through clinical note review. Tissue blocks were retrieved to determine immunohistochemical expression of p53 and HMGCR in tissue microarrays and the presence of KRAS mutations in extracted DNA. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for colorectal cancer-specific and overall survival. Statin use was not associated with improved cancer-specific survival in this cohort (HR=0.91, 95% CI 0.64–1.28). Statin use was also not associated with improved survival when the analyses were stratified by tumour p53 (wild-type HR=1.31, 95% CI 0.67–2.56 vs aberrant HR=0.80, 95% CI 0.52–1.24), HMGCR (HMGCR-high HR=0.69, 95% CI 0.40–1.18 vs HMGCR-low HR=1.10, 95% CI 0.66–1.84), and KRAS (wild-type HR=0.73, 95% CI 0.44–1.19 vs mutant HR=1.21, 95% CI 0.70–2.21) status. Statin use was not associated with improved survival either independently or when stratified by potential mevalonate pathway biomarkers in this population-based cohort of colon cancer patients.
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影响因子：
2.6
作者：
Bengtsson E;Nerjovaj P;Wangefjord S;Nodin B;Eberhard J;Uhlén M;Borgquist S;Jirström K
通讯作者：
Jirström K
DOI：
10.1016/s1470-2045(14)70119-6
发表时间：
2014-09
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Ahern TP;Lash TL;Damkier P;Christiansen PM;Cronin-Fenton DP
通讯作者：
Cronin-Fenton DP
影响因子：
45.3
作者：
Cardwell, Chris R.;Hicks, Blanaid M.;Murray, Liam J.
通讯作者：
Murray, Liam J.
影响因子：
7.4
作者：
Brennan, Donal J.;Laursen, Henriette;Jirstrom, Karin
通讯作者：
Jirstrom, Karin
DOI：
10.1158/1940-6207.capr-11-0113
发表时间：
2011-11
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Lee JE;Baba Y;Ng K;Giovannucci E;Fuchs CS;Ogino S;Chan AT
通讯作者：
Chan AT