Do discordant cancers share familial susceptibility?
Do discordant cancers share familial susceptibility?
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DOI：
10.1016/j.ejca.2011.09.017
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发表时间：
2012-05-01
影响因子：
8.4
通讯作者：
Brandt, Andreas
中科院分区：
文献类型：
--
作者：
Hemminki, Kari;Sundquist, Jan;Brandt, Andreas
目的：癌症综合征表现在许多部位，尽管外显率不同。全基因组关联(GWA)研究已经确定了许多类型癌症共有的易感基因。然而，由于缺乏人口规模，人群水平上对不协调癌症之间共同易感性的搜索受到阻碍。方法：在全国范围内的瑞典家庭癌症数据库中，对33个地点的110多万名患者进行了不协调家族性癌症的分析。标准化发病率比率(SIRS)是针对家庭成员患有明确癌症的患者与那些没有患癌症的家庭成员进行比较而计算的。结果：肺癌显示出13个显著不一致的关联，但大多数与吸烟是危险因素的站点有关。一个例外是肺癌和内分泌癌的聚集性。四个不协调的关联达到了5x10(-6)的最低显著水平：结直肠-子宫内膜、乳房-卵巢、乳房-前列腺癌和皮肤黑色素瘤-鳞状细胞癌。黑色素瘤和神经系统癌症的相关性达到了10(-4)的最小意义。剔除肺癌后，所有其他关联都基于单一检验，因此它们容易成为机会关联。结论：这项研究表明，在研究多个癌症部位时，对统计能力的要求非常高。除了与吸烟相关的网站外，乳腺癌和前列腺癌、黑色素瘤和神经系统肿瘤以及肺部和内分泌肿瘤之间的关联也得到了强有力的统计支持。在目前的样本数量限制内，我们没有发现任何证据表明总体上对癌症的易感性。(C)2011爱思唯尔有限公司。保留所有权利。
Aims: Cancer syndromes manifest at many sites albeit with variable penetrance. Genome-wide association (GWA) studies have identified susceptibility loci shared by many types of cancer. Yet, a population level search for shared susceptibility between discordant cancers has been hampered because of lacking population sizes.Methods: Over 1.1 million patients in the nation-wide Swedish Family-Cancer Database were analysed for discordant familial cancers covering 33 sites. Standardised incidence ratios (SIRs) were calculated for patients whose family members had a defined cancer compared to those whose family members did not have that cancer. Three independent tests for each pair of cancer sites were done using different family relationships.Results: Lung cancer showed 13 significant discordant associations but most of them were with sites for which smoking is a risk factor. An exception was the clustering of lung cancer and endocrine cancers. Four discordant associations reached a minimal significance level of 5 x 10(-6): colorectum-endometrium, breast-ovary, breast-prostate and melanoma-squamous cell carcinoma of the skin. The association of melanoma and nervous system cancer reached a minimal significance of 10(-4). Discarding lung cancer, all other associations were based on a single test whereby they were liable to be chance associations.Conclusions: This study showed the extraordinary requirements for statistical power in study of multiple cancer sites. In addition to the smoking related sites, associations between breast and prostate cancers, melanoma and nervous system tumours and lung and endocrine tumours found strong statistical support. Within the present sample size limits, we found no evidence of an overall susceptibility to cancer. (C) 2011 Elsevier Ltd. All rights reserved.