Huntsman Cancer Institute, University of Utah, Salt Lake City2Division of Gastroenterology, Department of Medicine, University of Utah, Salt Lake City.
Huntsman Cancer Institute, University of Utah, Salt Lake City3Department of Population Sciences, University of Utah, Salt Lake City4Department of Family and Consumer Studies, University of Utah, Salt Lake City.
JAMA Oncol. 2016 Mar;2(3):340-6. doi: 10.1001/jamaoncol.2015.4265.
Carcinoma of unknown primary (CUP) accounts for 3% to 5% of all cancers and is associated with poor prognosis. Familial clustering of different cancer sites with CUP is unknown and may provide information regarding etiology, as well as elevated cancer risks in relatives.
To quantify the risk of cancer by site in first- and second-degree relatives and first cousins of individuals with CUP.
DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study of patients who received a diagnosis of CUP between 1980 and 2010 identified from the Utah Cancer Registry. Population controls with no CUP diagnosis were sex and age matched 10:1 to patients with CUP. Data about relatives were drawn from the Utah Population Database.
Familial aggregation of cancer risk in relatives of cases compared with controls using Cox regression analysis.
For the 4160 index patients (median [interquartile range] age, 72 [62-81] years; 47.6% male) who had received a diagnosis of CUP, first-degree relatives were at an elevated risk of CUP themselves (hazard ratio [HR], 1.35 [95% CI, 1.07-1.70]), as well as lung (HR, 1.37 [95% CI, 1.22-1.54]), pancreatic (HR, 1.28 [95% CI, 1.06-1.54]), myeloma (HR, 1.28 [95% CI, 1.01-1.62]), and non-Hodgkin lymphoma (HR, 1.16 [95% CI, >1.00-1.35]) cancers compared with controls without CUP. When the analysis was restricted to relatives of cancer-free controls, additional increased risks for colon (HR, 1.19 [95% CI, 1.06-1.33]) and bladder (HR, 1.18 [95% CI, >1.00-1.38]) cancers were observed. Second-degree relatives of patients with CUP were at a slight increased risk of lung (HR, 1.14 [95% CI, 1.03-1.26]), pancreatic (HR, 1.17 [95% CI, 1.01-1.37]), breast (HR, 1.09 [95% CI, 1.02-1.16]), melanoma (HR, 1.09 [95% CI, >1.00-1.19]), and ovarian (HR, 1.19 [95% CI, 1.02-1.39]) cancers.
Relatives of patients with CUP are at increased risk of CUP and several other malignant neoplasms, including lung, pancreatic, and colon cancer. The present data may suggest sites of origin for CUP and provide cancer risk information for relatives of patients with CUP that can lead to effective intervention. Relatives of patients with CUP should be aware of the elevated risks for lung, pancreatic, and colon cancer and encouraged to modify risk factors and adhere to site-specific population cancer screening.
未知原发性癌（CUP）占所有癌症的 3%至 5%，与预后不良相关。家族聚集的不同癌症部位与 CUP 尚不清楚，可能提供有关病因学的信息，以及亲属的癌症风险升高。
定量分析 CUP 患者一级和二级亲属以及表亲的癌症风险。
设计、设置和参与者：对 1980 年至 2010 年间从犹他癌症登记处确诊的 CUP 患者进行病例对照嵌套研究。没有 CUP 诊断的人群对照按性别和年龄 10:1 与 CUP 患者匹配。关于亲属的数据来自犹他州人口数据库。
Cox 回归分析比较病例与对照的亲属癌症风险聚集情况。
在 4160 名确诊 CUP 的指数患者（中位[四分位间距]年龄，72[62-81]岁；47.6%为男性）中，一级亲属自身 CUP 风险增加（风险比[HR]，1.35[95%CI，1.07-1.70]），以及肺癌（HR，1.37[95%CI，1.22-1.54]）、胰腺癌（HR，1.28[95%CI，1.06-1.54]）、骨髓瘤（HR，1.28[95%CI，1.01-1.62]）和非霍奇金淋巴瘤（HR，1.16[95%CI，>1.00-1.35]）与无 CUP 对照组相比。当将分析仅限于无癌症对照组的亲属时，观察到结直肠癌（HR，1.19[95%CI，1.06-1.33]）和膀胱癌（HR，1.18[95%CI，>1.00-1.38]）的风险进一步增加。CUP 患者的二级亲属患肺癌（HR，1.14[95%CI，1.03-1.26]）、胰腺癌（HR，1.17[95%CI，1.01-1.37]）、乳腺癌（HR，1.09[95%CI，1.02-1.16]）、黑色素瘤（HR，1.09[95%CI，>1.00-1.19]）和卵巢癌（HR，1.19[95%CI，1.02-1.39]）的风险略有增加。
CUP 患者的亲属患 CUP 和其他几种恶性肿瘤的风险增加，包括肺癌、胰腺癌和结肠癌。目前的数据可能提示 CUP 的起源部位，并为 CUP 患者的亲属提供癌症风险信息，从而进行有效的干预。CUP 患者的亲属应意识到肺癌、胰腺癌和结肠癌的风险增加，并鼓励他们改变风险因素并遵守特定部位的人群癌症筛查。
