Risk of Different Cancers Among First-degree Relatives of Pancreatic Cancer Patients: Influence of Probands' Susceptibility Gene Mutation Status

Samuel Antwi, Sarah E. Fagan, Kari G. Chaffee, William R. Bamlet, Chunling Hu, Eric Polley, Steven Hart, Hermela Shimelis, Jenna Lilyquist, Rohan D. Gnanaolivu, Robert R Mc Williams, Ann L Oberg, Fergus J Couch, Gloria M Petersen

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Abstract

BACKGROUND: Increased risk of malignancies other than pancreatic cancer (PC) has been reported among first-degree relatives (FDRs) of PC patients; however, the roles of susceptibility gene mutations are unclear. We assessed risk for 15 cancers among FDRs of unselected PC probands. METHODS: Data on 17 162 FDRs, with more than 336 000 person-years at risk, identified through 2305 sequential PC probands enrolled at Mayo Clinic (2000-2016) were analyzed. Family history data were provided by the probands. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated, comparing malignancies observed among the FDRs with that expected using Surveillance, Epidemiology, and End Results (SEER) data. Genetic testing was performed among a subset of probands (n = 2094), enabling stratified analyses among FDRs based on whether the related proband tested positive or negative for inherited mutation in 22 sequenced cancer susceptibility genes. All statistical tests were two-sided. RESULTS: Compared with SEER, PC risk was twofold higher among FDRs of PC probands (SIR = 2.04, 95% CI = 1.78 to 2.31, P < .001). Primary liver cancer risk was elevated among female FDRs (SIR = 2.10, 95% CI = 1.34 to 3.12, P < .001). PC risk was more elevated among FDRs of mutation-positive probands (SIR = 4.32, 95% CI = 3.10 to 5.86) than FDRs of mutation-negative probands (SIR = 1.77, 95% CI = 1.51 to 2.05, between-group P < .001). FDR PC risk was higher when the related proband was younger than age 60 years at diagnosis and mutation-positive (SIR = 5.24, 95% CI = 2.93 to 8.64) than when the proband was younger than age 60 years but mutation-negative (SIR = 1.76, 95% CI = 1.21 to 2.47, between-group P < .001). Breast (SIR = 1.29, 95% CI = 1.01 to 1.63) and ovarian (SIR = 2.38, 95% CI = 1.30 to 4.00) cancers were elevated among FDRs of mutation-positive probands. CONCLUSIONS: Our study substantiates twofold risk of PC among FDRs of PC patients and suggests increased risk for primary liver cancer among female FDRs. FDRs of susceptibility mutation carriers had substantially increased risk for PC and increased risk for breast and ovarian cancers.

Original languageEnglish (US)
Pages (from-to)264-271
Number of pages8
JournalJournal of the National Cancer Institute
Volume111
Issue number3
DOIs
StatePublished - Mar 1 2019

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Pancreatic Neoplasms
Mutation
Genes
Confidence Intervals
Neoplasms
Incidence
Liver Neoplasms
Epidemiology
Neoplasm Genes
Genetic Testing
Ovarian Neoplasms
Breast

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Risk of Different Cancers Among First-degree Relatives of Pancreatic Cancer Patients : Influence of Probands' Susceptibility Gene Mutation Status. / Antwi, Samuel; Fagan, Sarah E.; Chaffee, Kari G.; Bamlet, William R.; Hu, Chunling; Polley, Eric; Hart, Steven; Shimelis, Hermela; Lilyquist, Jenna; Gnanaolivu, Rohan D.; Mc Williams, Robert R; Oberg, Ann L; Couch, Fergus J; Petersen, Gloria M.

In: Journal of the National Cancer Institute, Vol. 111, No. 3, 01.03.2019, p. 264-271.

Research output: Contribution to journalArticle

@article{dff1565519ab474389fc915080656acb,
title = "Risk of Different Cancers Among First-degree Relatives of Pancreatic Cancer Patients: Influence of Probands' Susceptibility Gene Mutation Status",
abstract = "BACKGROUND: Increased risk of malignancies other than pancreatic cancer (PC) has been reported among first-degree relatives (FDRs) of PC patients; however, the roles of susceptibility gene mutations are unclear. We assessed risk for 15 cancers among FDRs of unselected PC probands. METHODS: Data on 17 162 FDRs, with more than 336 000 person-years at risk, identified through 2305 sequential PC probands enrolled at Mayo Clinic (2000-2016) were analyzed. Family history data were provided by the probands. Standardized incidence ratios (SIRs) and 95{\%} confidence intervals (CIs) were calculated, comparing malignancies observed among the FDRs with that expected using Surveillance, Epidemiology, and End Results (SEER) data. Genetic testing was performed among a subset of probands (n = 2094), enabling stratified analyses among FDRs based on whether the related proband tested positive or negative for inherited mutation in 22 sequenced cancer susceptibility genes. All statistical tests were two-sided. RESULTS: Compared with SEER, PC risk was twofold higher among FDRs of PC probands (SIR = 2.04, 95{\%} CI = 1.78 to 2.31, P < .001). Primary liver cancer risk was elevated among female FDRs (SIR = 2.10, 95{\%} CI = 1.34 to 3.12, P < .001). PC risk was more elevated among FDRs of mutation-positive probands (SIR = 4.32, 95{\%} CI = 3.10 to 5.86) than FDRs of mutation-negative probands (SIR = 1.77, 95{\%} CI = 1.51 to 2.05, between-group P < .001). FDR PC risk was higher when the related proband was younger than age 60 years at diagnosis and mutation-positive (SIR = 5.24, 95{\%} CI = 2.93 to 8.64) than when the proband was younger than age 60 years but mutation-negative (SIR = 1.76, 95{\%} CI = 1.21 to 2.47, between-group P < .001). Breast (SIR = 1.29, 95{\%} CI = 1.01 to 1.63) and ovarian (SIR = 2.38, 95{\%} CI = 1.30 to 4.00) cancers were elevated among FDRs of mutation-positive probands. CONCLUSIONS: Our study substantiates twofold risk of PC among FDRs of PC patients and suggests increased risk for primary liver cancer among female FDRs. FDRs of susceptibility mutation carriers had substantially increased risk for PC and increased risk for breast and ovarian cancers.",
author = "Samuel Antwi and Fagan, {Sarah E.} and Chaffee, {Kari G.} and Bamlet, {William R.} and Chunling Hu and Eric Polley and Steven Hart and Hermela Shimelis and Jenna Lilyquist and Gnanaolivu, {Rohan D.} and {Mc Williams}, {Robert R} and Oberg, {Ann L} and Couch, {Fergus J} and Petersen, {Gloria M}",
year = "2019",
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T1 - Risk of Different Cancers Among First-degree Relatives of Pancreatic Cancer Patients

T2 - Influence of Probands' Susceptibility Gene Mutation Status

AU - Antwi, Samuel

AU - Fagan, Sarah E.

AU - Chaffee, Kari G.

AU - Bamlet, William R.

AU - Hu, Chunling

AU - Polley, Eric

AU - Hart, Steven

AU - Shimelis, Hermela

AU - Lilyquist, Jenna

AU - Gnanaolivu, Rohan D.

AU - Mc Williams, Robert R

AU - Oberg, Ann L

AU - Couch, Fergus J

AU - Petersen, Gloria M

PY - 2019/3/1

Y1 - 2019/3/1

N2 - BACKGROUND: Increased risk of malignancies other than pancreatic cancer (PC) has been reported among first-degree relatives (FDRs) of PC patients; however, the roles of susceptibility gene mutations are unclear. We assessed risk for 15 cancers among FDRs of unselected PC probands. METHODS: Data on 17 162 FDRs, with more than 336 000 person-years at risk, identified through 2305 sequential PC probands enrolled at Mayo Clinic (2000-2016) were analyzed. Family history data were provided by the probands. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated, comparing malignancies observed among the FDRs with that expected using Surveillance, Epidemiology, and End Results (SEER) data. Genetic testing was performed among a subset of probands (n = 2094), enabling stratified analyses among FDRs based on whether the related proband tested positive or negative for inherited mutation in 22 sequenced cancer susceptibility genes. All statistical tests were two-sided. RESULTS: Compared with SEER, PC risk was twofold higher among FDRs of PC probands (SIR = 2.04, 95% CI = 1.78 to 2.31, P < .001). Primary liver cancer risk was elevated among female FDRs (SIR = 2.10, 95% CI = 1.34 to 3.12, P < .001). PC risk was more elevated among FDRs of mutation-positive probands (SIR = 4.32, 95% CI = 3.10 to 5.86) than FDRs of mutation-negative probands (SIR = 1.77, 95% CI = 1.51 to 2.05, between-group P < .001). FDR PC risk was higher when the related proband was younger than age 60 years at diagnosis and mutation-positive (SIR = 5.24, 95% CI = 2.93 to 8.64) than when the proband was younger than age 60 years but mutation-negative (SIR = 1.76, 95% CI = 1.21 to 2.47, between-group P < .001). Breast (SIR = 1.29, 95% CI = 1.01 to 1.63) and ovarian (SIR = 2.38, 95% CI = 1.30 to 4.00) cancers were elevated among FDRs of mutation-positive probands. CONCLUSIONS: Our study substantiates twofold risk of PC among FDRs of PC patients and suggests increased risk for primary liver cancer among female FDRs. FDRs of susceptibility mutation carriers had substantially increased risk for PC and increased risk for breast and ovarian cancers.

AB - BACKGROUND: Increased risk of malignancies other than pancreatic cancer (PC) has been reported among first-degree relatives (FDRs) of PC patients; however, the roles of susceptibility gene mutations are unclear. We assessed risk for 15 cancers among FDRs of unselected PC probands. METHODS: Data on 17 162 FDRs, with more than 336 000 person-years at risk, identified through 2305 sequential PC probands enrolled at Mayo Clinic (2000-2016) were analyzed. Family history data were provided by the probands. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated, comparing malignancies observed among the FDRs with that expected using Surveillance, Epidemiology, and End Results (SEER) data. Genetic testing was performed among a subset of probands (n = 2094), enabling stratified analyses among FDRs based on whether the related proband tested positive or negative for inherited mutation in 22 sequenced cancer susceptibility genes. All statistical tests were two-sided. RESULTS: Compared with SEER, PC risk was twofold higher among FDRs of PC probands (SIR = 2.04, 95% CI = 1.78 to 2.31, P < .001). Primary liver cancer risk was elevated among female FDRs (SIR = 2.10, 95% CI = 1.34 to 3.12, P < .001). PC risk was more elevated among FDRs of mutation-positive probands (SIR = 4.32, 95% CI = 3.10 to 5.86) than FDRs of mutation-negative probands (SIR = 1.77, 95% CI = 1.51 to 2.05, between-group P < .001). FDR PC risk was higher when the related proband was younger than age 60 years at diagnosis and mutation-positive (SIR = 5.24, 95% CI = 2.93 to 8.64) than when the proband was younger than age 60 years but mutation-negative (SIR = 1.76, 95% CI = 1.21 to 2.47, between-group P < .001). Breast (SIR = 1.29, 95% CI = 1.01 to 1.63) and ovarian (SIR = 2.38, 95% CI = 1.30 to 4.00) cancers were elevated among FDRs of mutation-positive probands. CONCLUSIONS: Our study substantiates twofold risk of PC among FDRs of PC patients and suggests increased risk for primary liver cancer among female FDRs. FDRs of susceptibility mutation carriers had substantially increased risk for PC and increased risk for breast and ovarian cancers.

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