According to a paper published in the June 4 issue of JAMA, patients with advanced colon cancer who receive chemotherapy and who have a family history of colorectal cancer have a significantly lower likelihood of cancer recurrence and death. Jennifer A. Chan, M.D., M.P.H., (Dana-Farber Cancer Institute, Boston) and colleagues also note that the risk is reduced further in patients who have more first-degree relatives who have been affected by the disease.

In providing background information, the authors note that, “Approximately 16 percent to 20 percent of patients with colorectal cancer have a first-degree relative with colorectal cancer. Beyond rare but highly penetrant hereditary colorectal cancer syndromes, numerous studies have demonstrated that a history of colorectal cancer in a first-degree relative increases the risk of developing the disease by approximately 2-fold. However, the influence of family history on cancer recurrence and survival among patients with established colon cancer remains uncertain.”

The results of this study come from an examination of 1,087 patients with stage III colon cancer who were receiving supplemental chemotherapy. Researchers used information provided by the patients to analyze the link between family history of colorectal cancer and recurrence and survival. The participants also provided follow-up data until March 2007 for cancer recurrence and death, with a median follow-up time of 5.6 years.

The analysis revealed that 195 of the 1,087 patients (17.9%) had one or more first-degree relatives with colorectal cancer. Statistical models indicated that a family history of the disease was associated with a significant reduction in the risk of cancer recurrence or death. Specifically, those with a family history had a 28% lower risk for cancer recurrence or death compared to patients who lacked a family history. Cancer recurrence or death occurred in 57 of 195 patients (29%) with a family history of colorectal cancer and 343 of 892 patients (38%) without a family history. Patients with a family history also had a 26% reduction in risk of cancer recurrence alone and a 25% reduction in risk of death alone compared to those without a history.

Chan and colleagues also found that patients who had more affected family members seemed to have an increased benefit associated with family history. Having two more affected relatives decreased the risk for cancer recurrence or death by 51% compared with participants without a family history of colorectal cancer.

“Beyond rare, well-characterized hereditary colorectal cancer syndromes, our data support the hypothesis that a relatively common though less penetrant genetic predisposition may not only influence colorectal cancer risk but also patient survival. This finding may reflect a distinct underlying molecular and pathogenic mechanism in cancers that develop in the setting of a common (i.e., sporadic) family history,” the authors conclude. “Further studies are needed to more fully elucidate potential mechanisms by which a common family history may influence the outcome for patients with colorectal cancer.”

An accompanying editorial, written by Boris Pasche, M.D., Ph.D. (Northwestern University Feinberg School of Medicine, Chicago, and Contributing Editor, JAMA), calls for additional validation of these striking findings:

“If these intriguing findings are validated in other studies, family history may well become a new prognostic factor in colorectal cancer. Should this be the case, genome-wide association studies and tumor gene expression profiling studies will be warranted to identify germline and tumor-specific genetic features associated with a family history of colorectal cancer and favorable outcome following adjuvant chemotherapy.”

“Over the past 2 decades, some of the first major molecular genetics inroads were achieved through careful study of patients with a strong family history of colorectal cancer. The study by Chan et al suggests that family history of colorectal cancer will lead to the identification of novel genetic features predictive of response to chemotherapy. Familial colorectal cancer may therefore confirm its role as a genetics treasure trove for medical discovery,” concludes Dr. Pasche.

Association of Family History With Cancer Recurrence and Survival Among Patients With Stage III Colon Cancer
Jennifer A. Chan; Jeffrey A. Meyerhardt; Donna Niedzwiecki; Donna Hollis; Leonard B. Saltz; Robert J. Mayer; James Thomas; Paul Schaefer; Renaud Whittom; Alexander Hantel; Richard M. Goldberg; Robert S. Warren; Monica Bertagnolli; Charles S. Fuchs
JAMA (2008). 299[21]:2515-2523.
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Written by: Peter M Crosta