Early detection of cancer in the general population: a blinded case-control study of p53 autoantibodies in colorectal cancer.

Early detection of cancer in the general population: a blinded case-control study of p53 autoantibodies in colorectal cancer.
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DOI:
10.1038/bjc.2012.517
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发表时间:
2013-01-15
影响因子:
8.8
通讯作者:
Wandall, H. H.
Wandall, H. H.
中科院分区:
医学1区
文献类型:
--
作者:
Pedersen, J. W.;Gentry-Maharaj, A.;Fourkala, E-O;Dawnay, A.;Burnell, M.;Zaikin, A.;Pedersen, A. E.;Jacobs, I.;Menon, U.;Wandall, H. H.

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最近在高危人群中进行的癌症筛查试验的报告表明,在临床诊断之前可以检测到自身抗体。然而,关于自身抗体特征在一般人群癌症筛查中的作用的数据很少。信息p53肽从结直肠癌患者的血清中确定使用自身抗体微阵列与15聚体重叠肽覆盖完整的p53序列。在盲法病例对照研究中使用来自英国卵巢癌筛查协作试验的多模式组的储存血清评估所选肽,其中妇女每年提供血液样品。病例为招募后发生结直肠癌的绝经后女性,诊断前有2份或更多血清样本。对照组为年龄匹配的无癌症史的女性。随机分配到多模式组的50640名妇女随访中位数为6.8年(四分位数间距为5.9-8.4)。在101名女性中收到了结直肠癌通知,其中97名(297份样本)已同意进行次要研究。它们与97个对照(296个系列样品)1:1匹配。四种信息量最大的肽识别了25.8%的结直肠癌患者,特异性为95%。临床诊断前的中位提前时间为1.4(范围0.12-3.8)年。我们的研究结果表明,在一般人群中,在临床前疾病期间可检测到自身抗体特征,并且可能在癌症筛查中具有价值。特别是在结直肠癌筛查中,目前需要提高依从性,这表明p53自身抗体可能有助于风险分层。
Recent reports from cancer screening trials in high-risk populations suggest that autoantibodies can be detected before clinical diagnosis. However, there is minimal data on the role of autoantibody signatures in cancer screening in the general population. Informative p53 peptides were identified in sera from patients with colorectal cancer using an autoantibody microarray with 15-mer overlapping peptides covering the complete p53 sequence. The selected peptides were evaluated in a blinded case–control study using stored serum from the multimodal arm of the United Kingdom Collaborative Trial of Ovarian Cancer Screening where women gave annual blood samples. Cases were postmenopausal women who developed colorectal cancer following recruitment, with 2 or more serum samples preceding diagnosis. Controls were age-matched women with no history of cancer. The 50 640 women randomised to the multimodal group were followed up for a median of 6.8 (inter-quartile range 5.9–8.4) years. Colorectal cancer notification was received in 101 women with serial samples of whom 97 (297 samples) had given consent for secondary studies. They were matched 1 : 1 with 97 controls (296 serial samples). The four most informative peptides identified 25.8% of colorectal cancer patients with a specificity of 95%. The median lead time was 1.4 (range 0.12–3.8) years before clinical diagnosis. Our findings suggest that in the general population, autoantibody signatures are detectable during preclinical disease and may be of value in cancer screening. In colorectal cancer screening in particular, where the current need is to improve compliance, it suggests that p53 autoantibodies may contribute towards risk stratification.
DOI: 10.1038/bjc.2012.155
发表时间: 2012-06-05
影响因子: 8.8
作者:
Fourkala, E. O.;Gentry-Maharaj, A.;Burnell, M.;Ryan, A.;Manchanda, R.;Dawnay, A.;Jacobs, I.;Widschwendter, M.;Menon, U.
通讯作者: Menon, U.
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发表时间: 2011-11
影响因子: 1.9
作者:
Nielsen HJ;Jakobsen KV;Christensen IJ;Brünner N;Danish Study Group on Early Detection of Colorectal Cancer
通讯作者: Danish Study Group on Early Detection of Colorectal Cancer
DOI: 10.1186/1745-6215-12-61
发表时间: 2011-03-01
期刊: TRIALS
影响因子: 2.5
作者:
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通讯作者: Menon, Usha
DOI: 10.1038/nm0795-701
发表时间: 1995-07-01
期刊: NATURE MEDICINE
影响因子: 82.9
作者:
LUBIN, R;ZALCMAN, G;SOUSSI, T
通讯作者: SOUSSI, T
DOI: 10.1200/jco.2008.16.2388
发表时间: 2008-11-01
影响因子: 45.3
作者:
Qiu, Ji;Choi, Gina;Hanash, Samir M.
通讯作者: Hanash, Samir M.