Frank Christoph, Sundquist Jan, Yu Hongyao, Hemminki Akseli, Hemminki Kari
Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, Heidelberg, D-69120, Germany.
Center for Primary Health Care Research, Lund University, Malmö, 205 02, Sweden.
Int J Cancer. 2017 Apr 1;140(7):1510-1516. doi: 10.1002/ijc.30583. Epub 2017 Jan 20.
Relatives of cancer patients are at an increased risk of the same (concordant) cancer but whether they are at a risk for different (discordant) cancers is largely unknown - beyond well characterized hereditary cancer syndromes - but would be of major scientific and clinical interest. We therefore decided to resolve the issue by analyzing familial risks when family members were diagnosed with any discordant cancers. We compared the population impact of concordant to discordant familial cancer. The Swedish Family-Cancer Database (FCD) was used to calculate familial relative risks (RRs) for family members of cancer patients, for the 27 most common cancers. Population attributable fractions (PAFs) were estimated for concordant and discordant family histories. Discordant cancers in the family were detected as significant risk factors for the majority of cancers, although the corresponding RRs were modest compared to RRs for concordant cancers. Risks increased with the number of affected family members with the highest RRs for pancreatic (2.31), lung (1.69), kidney (1.98), nervous system (1.79) and thyroid cancers (3.28), when 5 or more family members were diagnosed with discordant cancers. For most cancers, the PAF for discordant family history exceeded that for concordant family history. Our findings suggest that there is an unspecific genetic predisposition to cancer with clinical consequences. We consider it unlikely that shared environmental risk factors could essentially contribute to the risks for diverse discordant cancers, which are likely driven by genetic predisposition. The identification of genes that moderately increase the risk for many cancers will be a challenge.
癌症患者的亲属患相同（一致）癌症的风险增加，但除了特征明确的遗传性癌症综合征外，他们患不同（不一致）癌症的风险在很大程度上尚不清楚，不过这将具有重大的科学和临床意义。因此，我们决定通过分析家庭成员被诊断患有任何不一致癌症时的家族风险来解决这个问题。我们比较了一致与不一致家族性癌症对人群的影响。瑞典家族癌症数据库（FCD）用于计算癌症患者家庭成员患27种最常见癌症的家族相对风险（RRs）。估计了一致和不一致家族史的人群归因分数（PAFs）。家族中的不一致癌症被检测为大多数癌症的显著风险因素，尽管与一致癌症的RRs相比，相应的RRs较小。风险随着受影响家庭成员数量的增加而增加，当5名或更多家庭成员被诊断患有不一致癌症时，胰腺癌（2.31）、肺癌（1.69）、肾癌（1.98）、神经系统癌（1.79）和甲状腺癌（3.28）的RRs最高。对于大多数癌症，不一致家族史的PAF超过了一致家族史的PAF。我们的研究结果表明，存在一种非特异性的癌症遗传易感性，具有临床后果。我们认为，共同的环境风险因素不太可能对多种不一致癌症的风险产生实质性影响，这些癌症可能是由遗传易感性驱动的。鉴定适度增加多种癌症风险的基因将是一项挑战。
