Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, D-69120, Heidelberg, Germany.
Center for Primary Health Care Research, Lund University, 205 02 Malmö, Sweden.
Sci Rep. 2017 Feb 15;7:42601. doi: 10.1038/srep42601.
A family history of cutaneous melanoma ('melanoma') is a well-established risk factor for melanoma. However, less is known about the possible familial associations of melanoma with other discordant cancers. A risk for discordant cancer may provide useful information about shared genetic and environmental risk factors and it may be relevant background data in clinical genetic counseling. Using the Swedish Family-Cancer Database, we assessed the relative risk (RR) for any cancer in families with increasing numbers of first-degree relatives diagnosed with melanoma, including multiple melanoma, and in reverse order RR for melanoma in families of multiple discordant cancers. Close to 9% of melanoma was familial; among these 92% were in 2-case families and 8% in families with 3 cases or more. Cancers that were associated with melanoma, in at least two independent analyses, included breast, prostate, colorectal, skin and nervous system cancers. Other associations included cancer of unknown primary, acute myeloid leukemia/myelofibrosis and Waldenström macroglobulinemia/myeloma. Significant results, which appear biologically plausible, were also obtained for rare nasal melanoma and mesothelioma. Although small samples sizes and multiple comparisons were of concern, many of the above associations were internally consistent and provide new diverse leads for discordant familial association of melanoma.
家族性皮肤黑色素瘤（“黑色素瘤”）病史是黑色素瘤的一个既定危险因素。然而，对于黑色素瘤与其他不同癌症之间可能存在的家族相关性了解较少。不同癌症的风险可能提供有关共同遗传和环境风险因素的有用信息，并且可能是临床遗传咨询中的相关背景数据。我们使用瑞典家族癌症数据库，评估了具有越来越多一级亲属被诊断患有黑色素瘤（包括多发性黑色素瘤）的家族中任何癌症的相对风险（RR），并按相反顺序评估了多发性不同癌症家族中黑色素瘤的 RR。近 9%的黑色素瘤具有家族性；其中 92%存在于 2 例家族中，8%存在于 3 例或更多例家族中。至少在两项独立分析中与黑色素瘤相关的癌症包括乳腺癌、前列腺癌、结直肠癌、皮肤癌和神经系统癌症。其他关联包括不明原发性癌症、急性髓系白血病/骨髓纤维化和瓦尔登斯特伦巨球蛋白血症/骨髓瘤。还获得了一些具有生物学意义的显著结果，包括罕见的鼻黑色素瘤和间皮瘤。尽管小样本量和多次比较令人担忧，但上述许多关联在内部是一致的，并为黑色素瘤的不同家族相关性提供了新的多样化线索。
