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Jennifer A. Chan, MD, MPH; Jeffrey A. Meyerhardt, MD, MPH; Donna Niedzwiecki, PhD; Donna Hollis, MS; Leonard B. Saltz, MD; Robert J. Mayer, MD; James Thomas, MD, PhD; Paul Schaefer, MD; Renaud Whittom, MD; Alexander Hantel, MD; Richard M. Goldberg, MD; Robert S. Warren, MD; Monica Bertagnolli, MD; Charles S. Fuchs, MD, MPH

JAMA. 2008;299(21):2515-2523.

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 Affiliations: Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (Drs Chan, Meyerhardt, Mayer, and Fuchs); Cancer and Leukemia Group B (CALGB) Statistical Center, Duke University Medical Center, Durham, North Carolina (Dr Niedzwiecki and Ms Hollis); Memorial Sloan-Kettering Cancer Center, New York, New York (Dr Saltz); Ohio State University, Columbus (Dr Thomas); Toledo Community Hospital Oncology Program Community Clinical Oncology Program, Toledo, Ohio (Dr Schaefer); Hôpital du Sacré-Coeur de Montréal, Montreal, Quebec, Canada (Dr Whittom); Loyola University Stritch School of Medicine, Maywood, Illinois (Dr Hantel); Department of Hematology/Oncology, University of North Carolina, Chapel Hill (Dr Goldberg); Division of Surgical Oncology, University of California at San Francisco (Dr Warren); and Division of Surgical Oncology, Brigham and Women's Hospital, Boston (Dr Bertagnolli).

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