June 6, 2008 Among patients with advanced colon cancer receiving treatment that includes chemotherapy, a family history of colorectal cancer is associated with a significant reduction in cancer recurrence and death, with the risk reduced further by having an increasing number of affected first-degree relatives, according to a new study.
"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 authors write.
Jennifer A. Chan, M.D., M.P.H., of the Dana-Farber Cancer Institute, Boston, and colleagues examined the association of family history of colorectal cancer with recurrence and survival of 1,087 patients with stage III colon cancer who were receiving supplemental chemotherapy. Patients provided information on family history of colorectal cancer at the beginning of the study, and were followed up until March 2007 for cancer recurrence and death (median [midpoint] follow-up, 5.6 years).
Among the 1,087 participants, 195 (17.9 percent) reported a family history of colorectal cancer in 1 or more first-degree relatives. The researchers found that a family history of colorectal cancer was associated with a significant reduction in the risk of cancer recurrence or death. Compared with patients without a family history, those with a family history had a 28 percent lower risk for cancer recurrence or death, which occurred in 57 of 195 patients (29 percent) with a family history of colorectal cancer compared with 343 of 892 patients (38 percent) without a family history.
Examining just the risk for cancer recurrence, patients with a family history of colorectal cancer had a 26 percent reduced risk compared with patients without a family history. Cancer recurrence occurred in 27 percent of patients with a family history of colorectal cancer and 35 percent of patients without a family history. The reduced risk of death for patients with a family history of colorectal cancer was 25 percent.
The apparent benefit associated with family history was stronger with an increasing number of affected family members. Compared with participants without a family history of colorectal cancer, participants with two or more affected relatives had a 51 percent lower risk for cancer recurrence or death.
"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 researchers write. "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."
Editorial: Familial Colorectal Cancer - A Genetics Treasure Trove for Medical Discovery
In an accompanying editorial, Boris Pasche, M.D., Ph.D., of the Northwestern University Feinberg School of Medicine, Chicago, and Contributing Editor, JAMA, comments on the results of the study by Chan and colleagues.
"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," Dr. Pasche writes. "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."
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- 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. Association of Family History With Cancer Recurrence and Survival Among Patients With Stage III Colon Cancer. JAMA, 2008;299(21):2515-2523
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