Association of family history with cancer recurrence and survival among patients with stage III colon cancer.
BACKGROUND
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.


METHODS
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.


METHODS
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.


CONCLUSIONS
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.
Division of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. jang@partners.org
Jennifer A
JA
Chan
Jeffrey A
JA
Meyerhardt
Donna
D
Niedzwiecki
Donna
D
Hollis
Leonard B
LB
Saltz
Robert J
RJ
Mayer
James
J
Thomas
Paul
P
Schaefer
Renaud
R
Whittom
Alexander
A
Hantel
Richard M
RM
Goldberg
Robert S
RS
Warren
Monica
M
Bertagnolli
Charles S
CS
Fuchs
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D053843:DNA Mismatch Repair; D005260:Female; D006801:Humans; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics / Q000378:metabolism; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000401:mortality; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011446:Prospective Studies; D012008:Recurrence; D016019:Survival Analysis
D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein