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Brian Wolpin, MD, MPH
A pair of proteins may help explain why people with surgically
removed colorectal cancer and who are overweight, physically inactive,
and follow a Western-pattern diet may have an increased risk of dying of
the disease or other causes, Dana-Farber Cancer Institute scientists
report in a new study.
The researchers found that in people who have undergone surgery for
colorectal cancer, the levels of two insulin-related proteins in their
blood before diagnosis predicted their chances of dying from the cancer
or other conditions.
Patients with high prediagnosis levels of insulin-like growth factor
binding protein-1 (IGFBP-1) were more than half as likely to succumb to
the disease, while those with high levels of C-peptide were nearly twice
as likely to die. The results are being published online by the Journal of Clinical Oncology on Dec. 8.
The study was the first to consider whether proteins whose blood
levels are influenced by lifestyle factors can be a gauge of a patient's
chances of surviving stage I-III colorectal cancer.
It was designed to explore why people with certain characteristics —
namely, obesity, physical inactivity, and an unhealthy diet — have an
increased risk of colon cancer, cancer recurrence, and death.
Such lifestyle factors can lead to high levels of circulating
insulin, a hormone that may bind directly to colon cancer cells and spur
their growth. High insulin levels also lead to lead to numerous
alterations in other blood proteins, which may influence cancer cell
"We don't know yet whether the two proteins identified in this study
are part of the actual mechanism that promotes colon cancer recurrence
or whether they are simply 'markers' for risk of colon cancer recurrence
and death," says the study's lead author, Brian Wolpin, MD, MPH, of
Dana-Farber and Brigham and Women's Hospital (BWH).
"But the results underscore the growing evidence that lifestyle
choices can have an impact on the risk of recurrence in patients with
surgically removed colorectal cancer."
Using data from the Nurses' Health Study and the Health Professionals
Follow-up Study — two long-term studies tracking participants' health —
investigators examined prediagnosis levels of four insulin-related
proteins in 373 people who later developed stage I-III colorectal
cancer. All four proteins are known to increase or decrease in response
to lifestyle factors such as overweight, physical inactivity, and poor
Levels of two of the proteins were unrelated to colon cancer
recurrence or death. The connection between IGFBP-1, C-peptide, and
mortality, however, was strong.
Patients with the highest levels of IGFBP-1 had a 56 percent lower
risk of death during the study period, and a 57 percent lower risk of
dying from colorectal cancer. Researchers speculate that the protein may
exert a protective effect by blocking other growth factors that
contribute to colon cancer cell proliferation.
High levels of C-peptide, by contrast, doubled the risk of overall
death in people with cancer but were not significantly associated with
death from colorectal cancer itself. This may be because of an even
stronger link between high insulin levels of other potentially fatal
diseases such as heart disease and stroke, or because C-peptide is not
as accurate a measure of insulin-related hormonal changes as other
proteins, the study authors speculate.
Funding for the study was provided by grants from the National Cancer Institute.
The senior author of the paper is Charles Fuchs, MD, MPH, of
Dana-Farber and BWH. Co-authors were Jeffrey Meyerhardt, MD, MPH, Kimmie
Ng, MD, MPH, Jennifer Chan, MD, MPH, of Dana-Farber and BWH; Andrew
Chan, MD, MPH, of Massachusetts General Hospital and BWH; Kana Wu, MD,
PhD, of Harvard School of Public Health; Michael Pollak, MD, of the
Jewish General Hospital and McGill University in Montreal; and Edward
Giovannucci, MD, ScD, of BWH and the Harvard School of Public Health.
Dana-Farber Cancer Institute (www.dana-farber.org)
is a principal teaching affiliate of the Harvard Medical School and is
among the leading cancer research and care centers in the United States.
It is a founding member of the Dana-Farber/Harvard Cancer Center
(DF/HCC), designated a comprehensive cancer center by the National