title: Familial Risk in Patients With Carcinoma of Unknown Primary.
abstract: OBJECTIVE
  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.
  
  
  OBJECTIVE
  To quantify the risk of cancer by site in first- and second-degree relatives and first cousins of individuals with CUP.
  
  
  METHODS
  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.
  
  
  METHODS
  Familial aggregation of cancer risk in relatives of cases compared with controls using Cox regression analysis.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Huntsman Cancer Institute, University of Utah, Salt Lake City2Division of Gastroenterology, Department of Medicine, University of Utah, Salt Lake City.
authors: N Jewel
authors: NJ
authors: Samadder
authors: 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.
authors: Ken Robert
authors: KR
authors: Smith
authors: Huntsman Cancer Institute, University of Utah, Salt Lake City.
authors: Heidi
authors: H
authors: Hanson
authors: Huntsman Cancer Institute, University of Utah, Salt Lake City.
authors: Richard
authors: R
authors: Pimentel
authors: Huntsman Cancer Institute, University of Utah, Salt Lake City.
authors: Jathine
authors: J
authors: Wong
authors: Huntsman Cancer Institute, University of Utah, Salt Lake City.
authors: Kenneth
authors: K
authors: Boucher
authors: Huntsman Cancer Institute, University of Utah, Salt Lake City5Division of Medical Oncology, Department of Medicine, University of Utah, Salt Lake City.
authors: Wallace
authors: W
authors: Akerley
authors: Huntsman Cancer Institute, University of Utah, Salt Lake City5Division of Medical Oncology, Department of Medicine, University of Utah, Salt Lake City.
authors: Glynn
authors: G
authors: Gilcrease
authors: Huntsman Cancer Institute, University of Utah, Salt Lake City3Department of Population Sciences, University of Utah, Salt Lake City.
authors: Cornelia M
authors: CM
authors: Ulrich
authors: Huntsman Cancer Institute, University of Utah, Salt Lake City2Division of Gastroenterology, Department of Medicine, University of Utah, Salt Lake City6Department of Oncological Sciences, University of Utah, Salt Lake City.
authors: Randall W
authors: RW
authors: Burt
authors: Huntsman Cancer Institute, University of Utah, Salt Lake City7Division of Genetic Epidemiology, Department of Medicine, University of Utah, Salt Lake City.
authors: Karen
authors: K
authors: Curtin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000235:genetics; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D014589:Utah