Pashayan Nora, Duffy Stephen W, Neal David E, Hamdy Freddie C, Donovan Jenny L, Martin Richard M, Harrington Patricia, Benlloch Sara, Amin Al Olama Ali, Shah Mitul, Kote-Jarai Zsofia, Easton Douglas F, Eeles Rosalind, Pharoah Paul D
Department of Applied Health Research, University College London, London, UK.
Centre for Cancer Prevention, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK.
Genet Med. 2015 Oct;17(10):789-95. doi: 10.1038/gim.2014.192. Epub 2015 Jan 8.
This study aimed to quantify the probability of overdiagnosis of prostate cancer by polygenic risk.
We calculated the polygenic risk score based on 66 known prostate cancer susceptibility variants for 17,012 men aged 50-69 years (9,404 men identified with prostate cancer and 7,608 with no cancer) derived from three UK-based ongoing studies. We derived the probabilities of overdiagnosis by quartiles of polygenic risk considering that the observed prevalence of screen-detected prostate cancer is a combination of underlying incidence, mean sojourn time (MST), test sensitivity, and overdiagnosis.
Polygenic risk quartiles 1 to 4 comprised 9, 18, 25, and 48% of the cases, respectively. For a prostate-specific antigen test sensitivity of 80% and MST of 9 years, 43, 30, 25, and 19% of the prevalent screen-detected cancers in quartiles 1 to 4, respectively, were likely to be overdiagnosed cancers. Overdiagnosis decreased with increasing polygenic risk, with 56% decrease between the lowest and the highest polygenic risk quartiles.
Targeting screening to men at higher polygenic risk could reduce the problem of overdiagnosis and lead to a better benefit-to-harm balance in screening for prostate cancer.
本研究旨在量化多基因风险导致前列腺癌过度诊断的概率。
我们基于66个已知的前列腺癌易感性变异，为来自三项英国正在进行的研究中的17012名50 - 69岁男性（9404名被确诊为前列腺癌的男性和7608名未患癌的男性）计算多基因风险评分。考虑到筛查发现的前列腺癌的观察患病率是潜在发病率、平均停留时间（MST）、检测敏感性和过度诊断的综合结果，我们通过多基因风险四分位数得出过度诊断的概率。
多基因风险四分位数1至4分别包含9%、18%、25%和48%的病例。对于前列腺特异性抗原检测敏感性为80%且MST为9年的情况，四分位数1至4中筛查发现的前列腺癌病例中，分别有43%、30%、25%和19%可能是过度诊断的癌症。过度诊断随着多基因风险的增加而降低，最低和最高多基因风险四分位数之间降低了56%。
针对多基因风险较高的男性进行筛查可以减少过度诊断问题，并在前列腺癌筛查中实现更好的利弊平衡。
