Deoxyribonuclease I Activity, Cell-Free DNA, and Risk of Liver Cancer in a Prospective Cohort

医学 生物标志物 内科学 危险系数 前瞻性队列研究 癌症 置信区间 肝癌 队列 胃肠病学 四分位数 肿瘤科 套式病例对照研究 队列研究 优势比 生物 生物化学
作者
Rachel M. Golonka,Beng San Yeoh,Jessica L. Petrick,Stephanie J. Weinstein,Demetrius Albanes,Andrew T. Gewirtz,Katherine A. McGlynn,Matam Vijay‐Kumar
出处
期刊:JNCI Cancer Spectrum [Oxford University Press]
卷期号:2 (4) 被引量:13
标识
DOI:10.1093/jncics/pky083
摘要

Abstract Background Circulating cell-free DNA (cfDNA) is a proposed latent biomarker for several cancers, including liver cancer. Deoxyribonucleases (DNases) facilitate the timely and efficient degradation of cfDNA, leading us to hypothesize that DNase I and/or II might be a more sensitive early biomarker than cfDNA. To test this hypothesis, a study was conducted in a large, prospective cohort. Methods A nested case-control study (224 liver cancer case patients and 224 matched control subjects) was conducted in a cohort of Finnish male smokers, followed from baseline (1985–1988) to 2014. The associations among DNase I activity, cfDNA, and the risk of liver cancer were assessed using multivariable-adjusted conditional logistic regression. Results DNase I activity, whether measured as radius (mm) or as units per milliliter, was statistically significantly associated with increased risk of liver cancer (Ptrend <.01). DNase I activity in the highest quartile was associated with a greater than threefold risk of developing liver cancer (DNase I activity radius >2.7 mm, hazard ratio [HR] = 3.03, 95% confidence interval [CI] = 1.59 to 5.77; DNase I activity >2.72 units/mL, HR = 3.30, 95% CI = 1.64 to 6.65). The strength of this association was not substantially altered by exclusion of cases diagnosed within the first five years of follow-up or those with hepatitis C virus (HCV) infection. In contrast, cfDNA and DNase II was not statistically significantly associated with risk of liver cancer. Conclusions DNase I activity was a superior latent biomarker of liver cancer than cfDNA. These findings advance the goal of developing a means to detect liver cancer years well before the development of clinical manifestations.
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