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兄弟前列腺癌患者中非低危疾病的一致性。

Concordance of Non-Low-Risk Disease Among Pairs of Brothers With Prostate Cancer.

机构信息

Fredrik Jansson, Thomas Frisell, and Olof Akre, Karolinska Institute; Olof Akre, Karolinska University Hospital; Fredrik Jansson, Danderyd Hospital, Stockholm; Linda Drevin, Regional Cancer Centre, Uppsala/Örebro; Pär Stattin, Uppsala University Hospital, Uppsala; and Ola Bratt, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

出版信息

J Clin Oncol. 2018 Jun 20;36(18):1847-1852. doi: 10.1200/JCO.2017.76.6907. Epub 2018 Apr 13.

Abstract

Purpose Prostate cancer among first-degree relatives is a strong risk factor for diagnosis of prostate cancer, and the contribution of heritable factors in prostate cancer etiology is high. We investigated how the concordance of non-low-risk prostate cancer among brothers is affected by their genetic relation. Methods We identified 4,262 pairs of brothers with prostate cancer in the Prostate Cancer Database Sweden. Their cancers were categorized as low risk (Gleason score ≤ 6; clinical stage T1-2, Nx/N0, Mx/M0; and prostate-specific antigen ≤ 10 ng/mL) or non-low risk. The odds ratio (OR) for concordance of non-low-risk cancer was calculated with logistic regression for the different types of fraternity (monozygotic twins, dizygotic twins, full brothers, and half-brothers) Results Among monozygotic twins who both were diagnosed with prostate cancer, the OR for both brothers being in the non-low-risk category was 3.82 (95% CI, 0.99 to 16.72) after adjusting for age and year of diagnosis. Among full brothers, the corresponding adjusted OR was 1.21 (95% CI, 1.04 to 1.39). When the analysis was restricted to brothers who both were diagnosed within 4 years, the results were similar. Conclusion Non-low-risk prostate cancer has a heritable pattern suggesting shared genetic factors, with the highest concordance among monozygotic twins. Our results suggest that a man whose brother has been diagnosed with a non-low-risk prostate cancer is at a clinically relevant increased risk of developing an aggressive prostate cancer himself.

摘要

目的

一级亲属(兄弟、姐妹、父母或子女)中有前列腺癌患者,是诊断为前列腺癌的一个强烈危险因素,遗传性因素在前列腺癌发病机制中占有很大比重。本研究旨在探讨兄弟间非低危前列腺癌的一致性是否受遗传关系的影响。

方法

我们在瑞典前列腺癌数据库中确定了 4262 对患有前列腺癌的兄弟。根据 Gleason 评分、临床分期、前列腺特异性抗原水平,将他们的肿瘤分为低危(Gleason 评分≤6;临床分期 T1-2,Nx/N0,Mx/M0;前列腺特异性抗原≤10ng/ml)和非低危。采用 logistic 回归计算不同类型兄弟(同卵双胞胎、异卵双胞胎、同父同母兄弟、同父异母兄弟)间非低危癌症一致性的比值比(OR)。

结果

在同时被诊断为前列腺癌的同卵双胞胎中,调整年龄和诊断年份后,同卵双胞胎均为非低危前列腺癌的 OR 为 3.82(95%可信区间,0.99 至 16.72)。在同父同母兄弟中,相应的调整后 OR 为 1.21(95%可信区间,1.04 至 1.39)。当将分析限制在诊断时间相差不超过 4 年的兄弟间时,结果相似。

结论

非低危前列腺癌具有遗传性模式,提示存在共同的遗传因素,同卵双胞胎间的一致性最高。我们的研究结果表明,兄弟中有人被诊断出患有非低危前列腺癌时,其自身患侵袭性前列腺癌的风险显著增加。

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