N Jewel Samadder1, Ken Robert Smith2, Heidi Hanson3, Richard Pimentel3, Jathine Wong3, Kenneth Boucher3, Wallace Akerley4, Glynn Gilcrease4, Cornelia M Ulrich5, Randall W Burt6, Karen Curtin7. 1. Huntsman Cancer Institute, University of Utah, Salt Lake City2Division of Gastroenterology, Department of Medicine, University of Utah, Salt Lake City. 2. 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. 3. Huntsman Cancer Institute, University of Utah, Salt Lake City. 4. Huntsman Cancer Institute, University of Utah, Salt Lake City5Division of Medical Oncology, Department of Medicine, University of Utah, Salt Lake City. 5. Huntsman Cancer Institute, University of Utah, Salt Lake City3Department of Population Sciences, University of Utah, Salt Lake City. 6. 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. 7. Huntsman Cancer Institute, University of Utah, Salt Lake City7Division of Genetic Epidemiology, Department of Medicine, University of Utah, Salt Lake City.
Abstract
IMPORTANCE: 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. 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. MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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.
IMPORTANCE: 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. 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. MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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: Divyanshoo R Kohli; Ken Robert Smith; Jathine Wong; Zhe Yu; Kenneth Boucher; Douglas O Faigel; Rahul Pannala; Randall W Burt; Karen Curtin; N Jewel Samadder Journal: J Gastroenterol Date: 2019-06-25 Impact factor: 7.527
Authors: Stefan Kolling; Ferdinando Ventre; Elena Geuna; Melissa Milan; Alberto Pisacane; Carla Boccaccio; Anna Sapino; Filippo Montemurro Journal: Front Oncol Date: 2020-01-17 Impact factor: 6.244
Authors: Alexander L R Grewcock; Karlijn E P E Hermans; Matty P Weijenberg; Piet A van den Brandt; Caroline Loef; Rob L H Jansen; Leo J Schouten Journal: Eur J Cancer Care (Engl) Date: 2021-07-05 Impact factor: 2.328