Department of Ophthalmology, The Ohio State University, Columbus, OH, USA.
Fam Cancer. 2010 Sep;9(3):431-8. doi: 10.1007/s10689-010-9328-7.
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. The extent of the contribution of familial/hereditary predisposition to the development of uveal melanoma is largely unknown. Thus we sought to ascertain the frequency of cancers in patients with UM and their family members to identify the prevalence of hereditary/familial predisposition to cancer in these patients. An unselected series of 121 patients with UM seen in a university-based tertiary referral program were consented to the study. Cancer histories (site and age of diagnosis) were obtained for all first- and second-degree relatives. Patients/families were classified as being potentially at high risk for hereditary predisposition if they met any of the following criteria: (1) Diagnosis of UM at age 30 or under, (2) Two or more cases of UM in the family, (3) UM plus at least one other primary cancer in the same patient (excluding non-melanoma skin and cervix cancers due to their strong environmental etiological link). (4) Family history meeting high risk criteria for a known hereditary cancer predisposition syndrome as defined by Hampel et al. (J Med Genet 41(2): 81-91, 2004). One patient had a family history of UM (0.8%). Ten patients (8.3%) had a personal and/or family history consistent with predisposition to a known hereditary cancer syndrome including six with possible hereditary breast, two with hereditary colon and two with hereditary melanomas. Twenty three patients (19%) had a personal history of a second cancer after exclusion of non-melanoma skin and cervical cancers. The frequency of cutaneous melanomas was significantly higher in UM patients than the general population (RR: 2.97, 95% CI: 1.00-6.94). Patients with a family history suggestive of a high risk predisposition to a known cancer syndrome had a significantly higher risk for having a second cancer than the remaining UM patients (P = 0.02). Our results indicate that the frequency of UM patients with high risk for a hereditary cancer predisposition is much higher than earlier estimates (0.6%) and that it could be as high as 11.6%. Our results suggest that cancer phenotypes in these patients are diverse and include cancers other than UM. Thus, alerting ophthalmologists to the need for expanding their cancer family history intake to include other cancers is warranted. It also suggests that patients with a hereditary predisposition to UM have a higher risk for the development of other cancers and that characterization of the germline genetic alterations in these patients is highly warranted.
葡萄膜黑色素瘤（UM）是成年人中最常见的原发性眼内恶性肿瘤。家族/遗传易感性对葡萄膜黑色素瘤发展的贡献程度在很大程度上尚不清楚。因此，我们试图确定 UM 患者及其家庭成员的癌症发病率，以确定这些患者中癌症遗传/家族易感性的患病率。在一个基于大学的三级转诊计划中，我们对 121 名未经选择的 UM 患者进行了研究。为所有一级和二级亲属获取了癌症病史（部位和诊断年龄）。如果患者/家属符合以下任何标准，则被认为具有遗传易感性的高风险：（1）30 岁或以下诊断为 UM，（2）家族中有两个或更多 UM 病例，（3）UM 加上同一患者中至少一种其他原发性癌症（由于其强烈的环境病因学联系，不包括非黑色素瘤皮肤和宫颈癌）。（4）家族史符合 Hampel 等人定义的已知遗传性癌症易感性综合征的高风险标准（J Med Genet 41(2): 81-91, 2004）。一名患者有 UM 家族史（0.8%）。10 名患者（8.3%）有个人和/或家族史，提示易患已知遗传性癌症综合征，包括 6 名可能遗传性乳腺癌、2 名遗传性结肠癌和 2 名遗传性黑色素瘤。排除非黑色素瘤皮肤和宫颈癌后，23 名患者（19%）有第二癌症病史。UM 患者的皮肤黑色素瘤发病率明显高于普通人群（RR：2.97，95%CI：1.00-6.94）。有家族史提示易患已知癌症综合征的遗传易感性的患者发生第二癌症的风险明显高于其余 UM 患者（P = 0.02）。我们的结果表明，具有遗传性癌症易感性高风险的 UM 患者的频率远高于早期估计（0.6%），可能高达 11.6%。我们的结果表明，这些患者的癌症表型多种多样，包括 UM 以外的癌症。因此，提醒眼科医生需要扩大其癌症家族史摄入量以包括其他癌症是合理的。这也表明，UM 遗传性易感性患者发生其他癌症的风险更高，非常有必要对这些患者的种系遗传改变进行特征描述。
