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.
Int J Cancer. 2017 Dec 1;141(11):2253-2259. doi: 10.1002/ijc.30927. Epub 2017 Aug 26.
Familial risks of breast cancer (BC) are well established but whether BC clusters with other, i.e. discordant, cancers is less certain but of interest for the identification of common genetic and possible environmental factors contributing to a general cancer susceptibility. We apply a novel approach to search for familial associations of BC with other (discordant) cancers based on the Swedish Family-Cancer Database. Relative risks (RRs) were calculated for BC in families with increasing numbers of patients with discordant cancer X, and conversely, familial RRs for cancer X in families with increasing numbers of BC patients. Joint p-values were calculated from independent analyses. The total number of familial BCs was 12,266, 14.9% with one first-degree relative with BC and 1.2% with at least 2 affected relatives. Ovarian and prostate cancers showed the strongest associations with BC (p-value <10 ). The p-value for melanoma was <10 , for stomach and male colorectal cancer <2.5 × 10 , for cancer of unknown primary <2.5 × 10 and for lung cancer <5 × 10 . Significance level <5 × 10 was reached with pancreatic cancer. The remaining associations (p < 0.0025) included thyroid, endometrial, testicular, eye cancers (uveal melanoma), nervous system and endocrine tumors and non-Hodgkin lymphoma. The RR for BC increased by increasing numbers of patients with any cancer in family members and it reached 1.62 when three or more family members were affected. The results suggest that BC shares susceptibility with a number of other cancers. This might alert genetic counselors and challenge approaches for gene and gene-environment identification.
家族性乳腺癌（BC）风险已得到充分证实，但 BC 是否与其他（即不一致）癌症聚集尚不确定，但对于确定导致一般癌症易感性的共同遗传和可能的环境因素很有意义。我们应用一种新方法，基于瑞典家族癌症数据库，搜索 BC 与其他（不一致）癌症的家族关联性。对于具有递增数量的不一致癌症 X 患者的家族，计算了 BC 的相对风险（RR），反之，对于具有递增数量的 BC 患者的家族，计算了癌症 X 的家族 RR。从独立分析中计算联合 p 值。家族性 BC 总数为 12,266 例，14.9%有 1 位一级亲属患有 BC，1.2%至少有 2 位亲属患病。卵巢癌和前列腺癌与 BC 的关联最强（p 值 <10）。黑色素瘤的 p 值 <10，胃癌和男性结直肠癌 <2.5×10，原发性不明癌症 <2.5×10，肺癌 <5×10。胰腺癌达到了 <5×10 的显著性水平。其余关联（p<0.0025）包括甲状腺癌、子宫内膜癌、睾丸癌、眼部癌症（葡萄膜黑色素瘤）、神经系统和内分泌肿瘤以及非霍奇金淋巴瘤。BC 的 RR 随家族成员中任何癌症患者数量的增加而增加，当三个或更多家庭成员受到影响时，RR 达到 1.62。结果表明，BC 与许多其他癌症具有易感性。这可能会提醒遗传咨询师，并对基因和基因-环境识别方法提出挑战。
