Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120, Heidelberg, Germany.
Cancer Gene Therapy Group, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Sci Rep. 2017 Jul 12;7(1):5243. doi: 10.1038/s41598-017-05732-z.
Colorectal cancer (CRC) has a strong familial component which extends to discordant cancers (ie non-CRC tumors). This is best seen in cancer syndromes such as hereditary non-polyposis colorectal cancer (HNPCC) which predisposes to several tumor types. Population-based family studies have also found discordant associations for CRC but they have included cancers which manifest in HNPCC, and there is no convincing evidence of discordant associations beyond the known syndromes. We address familial associations of non-CRC tumors with CRC using the resources of the Swedish Family-Cancer Database and applying a powerful approach of assessing familial relative risks in families of increasing numbers of patients with discordant cancers. Among 1.8 million cancer patients and over 200,000 CRC cases consistent familial associations of CRC was observed for several HNPCC related cancers. However, for small intestinal, pancreatic and nervous system cancers RRs remained essentially unchanged when potential HNPCC families were excluded, suggesting involvement of genes not related to HNPCC. Two independent associations of CRC were found for melanoma, thyroid and eye cancers and these appeared not to be related to known syndromes. A number of other cancers associated with CRC in single analyses and independent studies are required to assess the relevance of such findings.
结直肠癌（CRC）具有很强的家族成分，这种家族成分延伸至非 CRC 肿瘤（即非 CRC 肿瘤）。这种情况在遗传性非息肉病结直肠癌（HNPCC）等癌症综合征中表现得最为明显，HNPCC 易患多种肿瘤类型。基于人群的家族研究也发现了 CRC 的非一致性关联，但它们包括了在 HNPCC 中表现出来的癌症，并且除了已知的综合征之外，没有令人信服的证据表明存在非一致性关联。我们利用瑞典家族癌症数据库的资源，采用评估具有非一致性癌症的家族中患者数量不断增加的家族相对风险的强大方法，来研究非 CRC 肿瘤与 CRC 的家族相关性。在 180 万癌症患者和 20 多万例 CRC 病例中，对于几种与 HNPCC 相关的癌症，观察到 CRC 存在一致的家族相关性。然而，当排除潜在的 HNPCC 家族时，小肠、胰腺和神经系统癌症的 RR 基本保持不变，这表明存在与 HNPCC 无关的基因参与。发现 CRC 与黑色素瘤、甲状腺癌和眼癌存在两个独立的相关性，这些似乎与已知的综合征无关。需要对其他一些在单一分析和独立研究中与 CRC 相关的癌症进行评估，以评估这些发现的相关性。
