Faculty Collaboration Database

Association of family history with cancer recurrence and survival among patients with stage III colon cancer. JAMA 2008 Jun 04;299(21):2515-23

Date

06/05/2008

Pubmed ID

18523220

Pubmed Central ID

PMC3616330

DOI

10.1001/jama.299.21.2515

Scopus ID

2-s2.0-44649122161 (requires institutional sign-in at Scopus site)   69 Citations

Abstract

CONTEXT: A family history of colorectal cancer in a first-degree relative increases the risk of developing colorectal cancer. However, the influence of family history on cancer recurrence and survival among patients with established disease remains uncertain.

OBJECTIVE: To examine the association of family history of colorectal cancer with cancer recurrence and survival of patients with colon cancer.

DESIGN, SETTING, AND PARTICIPANTS: Prospective observational study of 1087 patients with stage III colon cancer enrolled in a randomized adjuvant chemotherapy trial (CALGB 89803) between April 1999 and May 2001. Patients provided data on family history at baseline and were followed up until March 2007 for disease recurrence and death (median follow-up, 5.6 years). In a subset of patients, we assessed microsatellite instability (MSI) and expression of the mismatch repair (MMR) proteins MLH1 and MSH2 in tumor specimens.

MAIN OUTCOME MEASURES: Disease-free survival, recurrence-free survival, and overall survival according to the presence or absence of a family history of colorectal cancer.

RESULTS: Among 1087 eligible patients, 195 (17.9%) reported a family history of colorectal cancer in a first-degree relative. Cancer recurrence or death occurred in 57 of 195 patients (29%; 95% confidence interval [CI], 23%-36%) with a family history of colorectal cancer and 343 of 892 patients (38%; 95% CI, 35%-42%) without a family history. Compared with patients without a family history, the adjusted hazard ratios (HRs) among those with 1 or more affected first-degree relatives were 0.72 (95% CI, 0.54-0.96) for disease-free survival, 0.74 (95% CI, 0.55-0.99) for recurrence-free survival, and 0.75 (95% CI, 0.54-1.05) for overall survival. This reduction in risk of cancer recurrence or death associated with a family history became stronger with an increasing number of affected first-degree relatives. Compared with participants without a family history of colorectal cancer, those with 1 affected relative had a multivariate HR of 0.77 (95% CI, 0.57-1.04) for disease-free survival. For participants with 2 or more affected relatives, we observed a greater reduction in risk (multivariate HR for disease-free survival, 0.49; 95% CI, 0.23-1.04; P for trend with increasing number of affected relatives = .01). The improved disease-free survival associated with a family history was independent of tumoral MSI or MMR status.

CONCLUSION: Among patients with stage III colon cancer receiving adjuvant chemotherapy, a family history of colorectal cancer is associated with a significant reduction in cancer recurrence and death.

Author List

Chan JA, Meyerhardt JA, Niedzwiecki D, Hollis D, Saltz LB, Mayer RJ, Thomas J, Schaefer P, Whittom R, Hantel A, Goldberg RM, Warren RS, Bertagnolli M, Fuchs CS

Author

James P. Thomas MD, PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adaptor Proteins, Signal Transducing
Adult
Aged
Aged, 80 and over
Colonic Neoplasms
DNA Mismatch Repair
Female
Humans
Male
Microsatellite Instability
Middle Aged
MutL Protein Homolog 1
MutS Homolog 2 Protein
Neoplasm Recurrence, Local
Nuclear Proteins
Prospective Studies
Recurrence
Survival Analysis