The heritability of prostate cancer in the Nordic Twin Study of Cancer.
The heritability of prostate cancer in the Nordic Twin Study of Cancer.
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DOI：
10.1158/1055-9965.epi-13-0568
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发表时间：
2014-11
期刊：
影响因子：
--
通讯作者：
Mucci LA
中科院分区：
文献类型：
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作者：
Hjelmborg JB;Scheike T;Holst K;Skytthe A;Penney KL;Graff RE;Pukkala E;Christensen K;Adami HO;Holm NV;Nuttall E;Hansen S;Hartman M;Czene K;Harris JR;Kaprio J;Mucci LA
前列腺癌被认为是最具遗传性的癌症，尽管人们对这种遗传贡献如何随年龄变化的情况知之甚少。为了解决这个问题，我们在北欧双胞胎癌症队列研究中进行了世界上最大的前瞻性研究，其中包括 18,680 对同卵同性男性双胞胎和 30,054 对异卵同性男性双胞胎。我们结合了事件发生时间分析来估计风险一致性和遗传力，同时考虑了死亡风险的审查和竞争风险，这是之前模拟癌症风险和责任的双胞胎研究中尚未考虑到的偏差的基本来源。前列腺癌的累积风险与背景人群相似。在所有年龄段，同卵双胞胎被诊断患有前列腺癌的同卵双胞胎的累积风险均高于异卵双胞胎。在一致受影响的配对中，MZ 配对的诊断间隔时间明显短于 DZ 配对（中位值分别为 3.8 年和 6.5 年）。遗传差异对罹患前列腺癌的风险和责任的变化有很大影响（遗传率=58%（95% CI 52%–63%）。即使诊断和筛查程序有所不同，遗传因素的相对贡献在整个年龄到晚年的过程中都是恒定的，并且存在显着的遗传异质性。基于人群的双胞胎队列的结果表明，在解决偏见来源时，遗传因素对患前列腺癌的风险更大。遗传因素的作用在不同年龄阶段始终很高。研究结果影响遗传和表观遗传标记的搜索以及框架预防努力。
Prostate cancer is thought to be the most heritable cancer, although little is known about how this genetic contribution varies across age. To address this question, we undertook the world's largest prospective study in the Nordic Twin Study of Cancer cohort, including 18,680 monozygotic and 30,054 dizygotic same sex male twin pairs. We incorporated time-to-event analyses to estimate the risk concordance and heritability while accounting for censoring and competing risks of death, essential sources of biases that have not been accounted for in previous twin studies modeling cancer risk and liability. The cumulative risk of prostate cancer was similar to that of the background population. The cumulative risk for twins whose co-twin was diagnosed with prostate cancer was greater for MZ than for DZ twins across all ages. Among concordantly affected pairs, the time between diagnoses was significantly shorter for MZ than DZ pairs (median 3.8 versus 6.5 years, respectively). Genetic differences contributed substantially to variation in both the risk and the liability (heritability=58% (95% CI 52%–63%) of developing prostate cancer. The relative contribution of genetic factors was constant across age through late life with substantial genetic heterogeneity even when diagnosis and screening procedures vary. Results from the population based twin cohort, indicate a greater genetic contribution to the risk of developing prostate cancer when addressing sources of bias. The role of genetic factors is consistently high across age Findings impact the search for genetic and epigenetic markers and frame prevention efforts.