Familial risk in patients with carcinoma of unknown primary

Niloy Jewel Samadder, Ken Robert Smith, Heidi Hanson, Richard Pimentel, Jathine Wong, Kenneth Boucher, Wallace Akerley, Glynn Gilcrease, Cornelia M. Ulrich, Randall W. Burt, Karen Curtin

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)340-345
Number of pages6
JournalJAMA oncology
Volume2
Issue number3
DOIs
StatePublished - Mar 1 2016
Externally publishedYes

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Carcinoma
Neoplasms
Pancreatic Neoplasms
Colonic Neoplasms
Lung Neoplasms
Lung
Population Control
Early Detection of Cancer
Non-Hodgkin's Lymphoma
Population
Cluster Analysis
Registries
Case-Control Studies
Melanoma
Colon
Urinary Bladder
Breast
Regression Analysis
Databases

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Samadder, N. J., Smith, K. R., Hanson, H., Pimentel, R., Wong, J., Boucher, K., ... Curtin, K. (2016). Familial risk in patients with carcinoma of unknown primary. JAMA oncology, 2(3), 340-345. https://doi.org/10.1001/jamaoncol.2015.4265

Familial risk in patients with carcinoma of unknown primary. / Samadder, Niloy Jewel; Smith, Ken Robert; Hanson, Heidi; Pimentel, Richard; Wong, Jathine; Boucher, Kenneth; Akerley, Wallace; Gilcrease, Glynn; Ulrich, Cornelia M.; Burt, Randall W.; Curtin, Karen.

In: JAMA oncology, Vol. 2, No. 3, 01.03.2016, p. 340-345.

Research output: Contribution to journalArticle

Samadder, NJ, Smith, KR, Hanson, H, Pimentel, R, Wong, J, Boucher, K, Akerley, W, Gilcrease, G, Ulrich, CM, Burt, RW & Curtin, K 2016, 'Familial risk in patients with carcinoma of unknown primary', JAMA oncology, vol. 2, no. 3, pp. 340-345. https://doi.org/10.1001/jamaoncol.2015.4265
Samadder NJ, Smith KR, Hanson H, Pimentel R, Wong J, Boucher K et al. Familial risk in patients with carcinoma of unknown primary. JAMA oncology. 2016 Mar 1;2(3):340-345. https://doi.org/10.1001/jamaoncol.2015.4265
Samadder, Niloy Jewel ; Smith, Ken Robert ; Hanson, Heidi ; Pimentel, Richard ; Wong, Jathine ; Boucher, Kenneth ; Akerley, Wallace ; Gilcrease, Glynn ; Ulrich, Cornelia M. ; Burt, Randall W. ; Curtin, Karen. / Familial risk in patients with carcinoma of unknown primary. In: JAMA oncology. 2016 ; Vol. 2, No. 3. pp. 340-345.
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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.",
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T1 - Familial risk in patients with carcinoma of unknown primary

AU - Samadder, Niloy Jewel

AU - Smith, Ken Robert

AU - Hanson, Heidi

AU - Pimentel, Richard

AU - Wong, Jathine

AU - Boucher, Kenneth

AU - Akerley, Wallace

AU - Gilcrease, Glynn

AU - Ulrich, Cornelia M.

AU - Burt, Randall W.

AU - Curtin, Karen

PY - 2016/3/1

Y1 - 2016/3/1

N2 - 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.

AB - 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.

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