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 1vs.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 (0vs.1vs.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.
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Jansson-Knodell
authors.affiliation: Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA.
authors.forename: Nathan R
authors.initials: NR
authors.lastname: Foster
authors.affiliation: Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Sargent
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Limburg
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Smyrk
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Sinicrope
authors.affiliation: Metro Minnesota Community Oncology Research Consortium, St. Louis Park, MN, USA.
authors.forename: Balkrishna
authors.initials: B
authors.lastname: Jahagirdar
authors.affiliation: The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Goldberg
authors.affiliation: Mayo Clinic, Rochester, MN, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Alberts
keywords: Outcomes; colorectal cancer; family history