JAMA Otolaryngol Head Neck Surg. 2014 May;140(5):423-7. doi: 10.1001/jamaoto.2014.78.
IMPORTANCE Determining the associated risk between papillary thyroid carcinoma (PTC) and cutaneous malignant melanoma (CM) and the rate of BRAF v600e mutation could help identify a common genetic component of these 2 cancers. OBJECTIVES To define the relative risk of PTC in patients with CM, and vice versa, and their first- through fifth-degree relatives and spouses by using a unique population research database; and to assess the rate of BRAF v600e mutation in a group of patients with both diagnoses. DESIGN, SETTING, AND PARTICIPANTS Retrospective rev iew using the Utah Population Database (which is linked to medical records and the Utah Cancer Registry from 1966 to 2011) and tissue analysis in a tertiary care facility. Included were 4460 patients diagnosed with PTC and 14 569 with CM in Utah between 1966 and 2011 and their first- through fifth-degree relatives and spouses. These were compared at a 5:1 ratio with matched, population-based controls. MAIN OUTCOMES AND MEASURES Statistically significant increased risk of PTC in patients with CM, and vice versa, and any first- through fifth-degree relatives and spouses; and a significantly higher rate of BRAF v600e mutation in patients with both PTC and CM than would be expected for each individual condition alone. RESULTS Patients with CM had a 2.3-fold increased risk (P < .001) of being diagnosed as having PTC compared with population-based matched controls. Conversely, patients with PTC had a 1.8-fold increased risk (P < .001) of developing CM. First- through fifth-degree relatives and spouses of patients with PTC or CM did not show a statistically significant increased risk. Eight patients with both cancer diagnoses had tissue specimens tested, of which 4 (50%) were found to be positive for the BRAF v600e mutation in either their PTC or CM specimen, and 3 (38%) were found positive in both. CONCLUSIONS AND RELEVANCE Patients with either PTC or CMhave an increased risk of developing the other cancer as a second primary malignant neoplasm. Tissue specimens from patients with both cancers show a high rate of BRAF v600e mutation. Translational studies are needed to better define the associated genetic predisposition between PTC and CM and to test the efficacy of and implementation techniques for treatment plans using BRAF mutation as a therapeutic target.
确定甲状腺乳头状癌（PTC）和皮肤恶性黑色素瘤（CM）之间的关联风险以及 BRAF v600e 突变的发生率，有助于确定这两种癌症的共同遗传成分。目的：利用独特的人群研究数据库，定义 CM 患者中 PTC 的相对风险，反之亦然，以及他们的一级至五级亲属和配偶；并评估一组同时患有这两种疾病的患者的 BRAF v600e 突变率。设计、设置和参与者：回顾性审查使用犹他州人群数据库（该数据库与 1966 年至 2011 年的医疗记录和犹他癌症登记处相关联）和三级医疗机构的组织分析。包括 1966 年至 2011 年期间在犹他州被诊断患有 PTC 的 4460 例患者和患有 CM 的 14569 例患者，以及他们的一级至五级亲属和配偶。将这些人与匹配的基于人群的对照以 5:1 的比例进行比较。主要结果和措施：CM 患者中 PTC 的发病率显著增加，反之亦然，任何一级至五级亲属和配偶；以及同时患有 PTC 和 CM 的患者中 BRAF v600e 突变的发生率明显高于每种单独疾病的预期。结果：与基于人群的匹配对照组相比，患有 CM 的患者被诊断为患有 PTC 的风险增加了 2.3 倍（P <.001）。相反，患有 PTC 的患者患 CM 的风险增加了 1.8 倍（P <.001）。PTC 或 CM 患者的一级至五级亲属和配偶没有显示出统计学上显著的风险增加。8 例同时患有这两种癌症的患者进行了组织标本检测，其中 4 例（50%）在其 PTC 或 CM 标本中检测到 BRAF v600e 突变阳性，3 例（38%）在两种标本中均检测到阳性。结论和相关性：患有 PTC 或 CM 的患者患另一种癌症作为第二原发性恶性肿瘤的风险增加。同时患有这两种癌症的患者的组织标本显示出高 BRAF v600e 突变率。需要进行转化研究，以更好地定义 PTC 和 CM 之间的遗传易感性，并测试使用 BRAF 突变作为治疗靶点的治疗计划的疗效和实施技术。
