Family history of colorectal cancer and its impact on survival in patients with resected stage III colon cancer: Results from NCCTG Trial N0147 (Alliance)

Claire L. Jansson-Knodell, Nathan R. Foster, Daniel J. Sargent, Paul John Limburg, Stephen N Thibodeau, Thomas Christopher Smyrk, Frank A Sinicrope, Balkrishna Jahagirdar, Richard M. Goldberg, Steven Robert Alberts

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Family history of colon cancer often portends increased risk of disease development; however, the prognostic significance of family history related to disease and survival outcomes is unclear. Methods: To investigate the relationship between family history of colorectal cancer and survival outcomes in stage III colon cancer patients, a prospective cohort of 1,935 patients with resected stage III colon cancer enrolled in a randomized controlled trial (N0147), comparing the standard of care FOLFOX to FOLFOX with cetuximab, was studied. Patients completed a baseline questionnaire on family history and were followed every 6 months until death or 5 years after randomization. Results: We examined the endpoints of disease-free survival (DFS), time to recurrence (TTR) and overall survival (OS), comparing patients with a positive versus negative family history of colorectal cancer. The adjusted hazard ratios (HRs) for patients with a positive family history were 0.95 [95% confidence interval (CI), 0.78-1.16] for DFS, 0.94 (95% CI, 0.76-1.16) for TTR, and 0.92 (95% CI, 0.74-1.15) for OS (all adjusted P>0.47). A non-significant trend toward improved DFS (P=0.17; adjusted P=0.34) was observed when 2 or more relatives were affected as compared to 0 relatives (multivariate HR: 0.72; 95% CI, 0.45-1.15), whereas subjects with histories of 0 or 1 affected relatives had similar DFS (multivariate HR for 1 vs. 0: 1.00; 95% CI, 0.81-1.24). Interactions of the molecular factors KRAS, BRAF, and MMR with family history were also explored. The only significant interaction was for deficient MMR (dMMR) and first-degree relatives with a family history of colorectal cancer (0 vs. 1 vs. 2+ relatives) for a benefit on OS (univariate P=0.001), which remained significant after adjusting for other factors (P=0.029). Conclusions: Among patients with stage III resected colon cancer treated with adjuvant FOLFOX, a family history of colorectal cancer did not significantly impact DFS, TTR, or OS outcomes, with the exception of patients with dMMR-expressing tumors.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalJournal of Gastrointestinal Oncology
Volume8
Issue number1
DOIs
StatePublished - 2017

Fingerprint

Colonic Neoplasms
Colorectal Neoplasms
Survival
Disease-Free Survival
Confidence Intervals
Recurrence
Standard of Care
Random Allocation
Randomized Controlled Trials

Keywords

  • Colorectal cancer
  • Family history
  • Outcomes

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

Cite this

Family history of colorectal cancer and its impact on survival in patients with resected stage III colon cancer : Results from NCCTG Trial N0147 (Alliance). / Jansson-Knodell, Claire L.; Foster, Nathan R.; Sargent, Daniel J.; Limburg, Paul John; Thibodeau, Stephen N; Smyrk, Thomas Christopher; Sinicrope, Frank A; Jahagirdar, Balkrishna; Goldberg, Richard M.; Alberts, Steven Robert.

In: Journal of Gastrointestinal Oncology, Vol. 8, No. 1, 2017, p. 1-11.

Research output: Contribution to journalArticle

@article{f6887df5ea584126b97d64502dba400b,
title = "Family history of colorectal cancer and its impact on survival in patients with resected stage III colon cancer: Results from NCCTG Trial N0147 (Alliance)",
abstract = "Background: Family history of colon cancer often portends increased risk of disease development; however, the prognostic significance of family history related to disease and survival outcomes is unclear. Methods: To investigate the relationship between family history of colorectal cancer and survival outcomes in stage III colon cancer patients, a prospective cohort of 1,935 patients with resected stage III colon cancer enrolled in a randomized controlled trial (N0147), comparing the standard of care FOLFOX to FOLFOX with cetuximab, was studied. Patients completed a baseline questionnaire on family history and were followed every 6 months until death or 5 years after randomization. Results: We examined the endpoints of disease-free survival (DFS), time to recurrence (TTR) and overall survival (OS), comparing patients with a positive versus negative family history of colorectal cancer. The adjusted hazard ratios (HRs) for patients with a positive family history were 0.95 [95{\%} confidence interval (CI), 0.78-1.16] for DFS, 0.94 (95{\%} CI, 0.76-1.16) for TTR, and 0.92 (95{\%} CI, 0.74-1.15) for OS (all adjusted P>0.47). A non-significant trend toward improved DFS (P=0.17; adjusted P=0.34) was observed when 2 or more relatives were affected as compared to 0 relatives (multivariate HR: 0.72; 95{\%} CI, 0.45-1.15), whereas subjects with histories of 0 or 1 affected relatives had similar DFS (multivariate HR for 1 vs. 0: 1.00; 95{\%} CI, 0.81-1.24). Interactions of the molecular factors KRAS, BRAF, and MMR with family history were also explored. The only significant interaction was for deficient MMR (dMMR) and first-degree relatives with a family history of colorectal cancer (0 vs. 1 vs. 2+ relatives) for a benefit on OS (univariate P=0.001), which remained significant after adjusting for other factors (P=0.029). Conclusions: Among patients with stage III resected colon cancer treated with adjuvant FOLFOX, a family history of colorectal cancer did not significantly impact DFS, TTR, or OS outcomes, with the exception of patients with dMMR-expressing tumors.",
keywords = "Colorectal cancer, Family history, Outcomes",
author = "Jansson-Knodell, {Claire L.} and Foster, {Nathan R.} and Sargent, {Daniel J.} and Limburg, {Paul John} and Thibodeau, {Stephen N} and Smyrk, {Thomas Christopher} and Sinicrope, {Frank A} and Balkrishna Jahagirdar and Goldberg, {Richard M.} and Alberts, {Steven Robert}",
year = "2017",
doi = "10.21037/jgo.2016.12.13",
language = "English (US)",
volume = "8",
pages = "1--11",
journal = "Journal of Gastrointestinal Oncology",
issn = "2078-6891",
publisher = "Pioneer Bioscience Publishing Company (PBPC)",
number = "1",

}

TY - JOUR

T1 - Family history of colorectal cancer and its impact on survival in patients with resected stage III colon cancer

T2 - Results from NCCTG Trial N0147 (Alliance)

AU - Jansson-Knodell, Claire L.

AU - Foster, Nathan R.

AU - Sargent, Daniel J.

AU - Limburg, Paul John

AU - Thibodeau, Stephen N

AU - Smyrk, Thomas Christopher

AU - Sinicrope, Frank A

AU - Jahagirdar, Balkrishna

AU - Goldberg, Richard M.

AU - Alberts, Steven Robert

PY - 2017

Y1 - 2017

N2 - Background: Family history of colon cancer often portends increased risk of disease development; however, the prognostic significance of family history related to disease and survival outcomes is unclear. Methods: To investigate the relationship between family history of colorectal cancer and survival outcomes in stage III colon cancer patients, a prospective cohort of 1,935 patients with resected stage III colon cancer enrolled in a randomized controlled trial (N0147), comparing the standard of care FOLFOX to FOLFOX with cetuximab, was studied. Patients completed a baseline questionnaire on family history and were followed every 6 months until death or 5 years after randomization. Results: We examined the endpoints of disease-free survival (DFS), time to recurrence (TTR) and overall survival (OS), comparing patients with a positive versus negative family history of colorectal cancer. The adjusted hazard ratios (HRs) for patients with a positive family history were 0.95 [95% confidence interval (CI), 0.78-1.16] for DFS, 0.94 (95% CI, 0.76-1.16) for TTR, and 0.92 (95% CI, 0.74-1.15) for OS (all adjusted P>0.47). A non-significant trend toward improved DFS (P=0.17; adjusted P=0.34) was observed when 2 or more relatives were affected as compared to 0 relatives (multivariate HR: 0.72; 95% CI, 0.45-1.15), whereas subjects with histories of 0 or 1 affected relatives had similar DFS (multivariate HR for 1 vs. 0: 1.00; 95% CI, 0.81-1.24). Interactions of the molecular factors KRAS, BRAF, and MMR with family history were also explored. The only significant interaction was for deficient MMR (dMMR) and first-degree relatives with a family history of colorectal cancer (0 vs. 1 vs. 2+ relatives) for a benefit on OS (univariate P=0.001), which remained significant after adjusting for other factors (P=0.029). Conclusions: Among patients with stage III resected colon cancer treated with adjuvant FOLFOX, a family history of colorectal cancer did not significantly impact DFS, TTR, or OS outcomes, with the exception of patients with dMMR-expressing tumors.

AB - Background: Family history of colon cancer often portends increased risk of disease development; however, the prognostic significance of family history related to disease and survival outcomes is unclear. Methods: To investigate the relationship between family history of colorectal cancer and survival outcomes in stage III colon cancer patients, a prospective cohort of 1,935 patients with resected stage III colon cancer enrolled in a randomized controlled trial (N0147), comparing the standard of care FOLFOX to FOLFOX with cetuximab, was studied. Patients completed a baseline questionnaire on family history and were followed every 6 months until death or 5 years after randomization. Results: We examined the endpoints of disease-free survival (DFS), time to recurrence (TTR) and overall survival (OS), comparing patients with a positive versus negative family history of colorectal cancer. The adjusted hazard ratios (HRs) for patients with a positive family history were 0.95 [95% confidence interval (CI), 0.78-1.16] for DFS, 0.94 (95% CI, 0.76-1.16) for TTR, and 0.92 (95% CI, 0.74-1.15) for OS (all adjusted P>0.47). A non-significant trend toward improved DFS (P=0.17; adjusted P=0.34) was observed when 2 or more relatives were affected as compared to 0 relatives (multivariate HR: 0.72; 95% CI, 0.45-1.15), whereas subjects with histories of 0 or 1 affected relatives had similar DFS (multivariate HR for 1 vs. 0: 1.00; 95% CI, 0.81-1.24). Interactions of the molecular factors KRAS, BRAF, and MMR with family history were also explored. The only significant interaction was for deficient MMR (dMMR) and first-degree relatives with a family history of colorectal cancer (0 vs. 1 vs. 2+ relatives) for a benefit on OS (univariate P=0.001), which remained significant after adjusting for other factors (P=0.029). Conclusions: Among patients with stage III resected colon cancer treated with adjuvant FOLFOX, a family history of colorectal cancer did not significantly impact DFS, TTR, or OS outcomes, with the exception of patients with dMMR-expressing tumors.

KW - Colorectal cancer

KW - Family history

KW - Outcomes

UR - http://www.scopus.com/inward/record.url?scp=85014313783&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85014313783&partnerID=8YFLogxK

U2 - 10.21037/jgo.2016.12.13

DO - 10.21037/jgo.2016.12.13

M3 - Article

AN - SCOPUS:85014313783

VL - 8

SP - 1

EP - 11

JO - Journal of Gastrointestinal Oncology

JF - Journal of Gastrointestinal Oncology

SN - 2078-6891

IS - 1

ER -