News from the Journal of Clinical Oncology

New data from a long-term, prospective study show that among people who were surgically treated for colorectal cancer, pre-diagnosis blood levels of two insulin-related proteins predicted the risk of subsequent death. Researchers found that patients with high pre-diagnosis levels of insulin-like growth factor binding protein-1 (IGFBP-1) had a more than 50 percent reduced risk of overall death and colorectal cancer death; conversely, high levels of C-peptide, a marker of insulin production, were associated with nearly twice the overall risk of death. The study was the first to analyze the association between insulin-related protein markers and mortality in people treated for stage I-III colorectal cancer. Certain lifestyle factors – such as obesity, physical inactivity and unhealthy diet – are known to promote high levels of insulin, which may bind to specific insulin receptors on a cancer cell's surface and fuel the growth of colon cancer. High levels of insulin are associated with increased C-peptide levels and depressed IGFBP-1.

"Our findings add to the growing evidence that lifestyle choices have an impact on the risk of recurrence and death in people with colorectal cancer that has been surgically removed," explained Brian M. Wolpin, MD, instructor of medicine at Harvard Medical School, attending physician at Dana-Farber Cancer Institute, and the study's lead author. "Although this research needs to be confirmed in additional studies, our findings provide insight into the biologic factors that may underlie the influence of diet, body type and physical activity on cancer outcomes in patients with colorectal cancer."

Dr. Wolpin and his colleagues examined the relationship between pre-diagnosis plasma levels of IGFBP-1 and C-peptide in 373 people who were later found to have stage I-III colorectal cancer between 1991 and 2004. All patients were participants in the Nurses' Health Study or the Health Professionals Follow-up Study, two large ongoing prospective studies evaluating the influence of lifestyle factors on various diseases.

The study showed that:

IGFBP-1 was associated with a protective effect. Patients with the highest levels of IGFBP-1 had a 56 percent reduction in the risk of death overall and a 57 percent reduction in the risk of colorectal cancer death specifically. IGFBP-1 may exert a protective effect by blocking other growth factors that contribute to colon cancer cell growth.

C-peptide level was an indicator of increased risk of death. High levels of C-peptide doubled the risk of overall death in people with cancer but were not significantly associated with death from colorectal cancer specifically.

Dr. Wolpin speculated that the lack of a significant association between C-peptide levels and colorectal cancer death could be due to a link between high insulin production and other potentially fatal diseases, such as heart disease and stroke, which may have strengthened the association between C-peptide and overall mortality. Alternatively, he noted that smaller numbers of colorectal cancer deaths may have obscured a statistically significant association with C-peptide.

ASCO Perspective
Nicholas Petrelli, MD, ASCO Spokesperson, and Medical Director, Helen F. Graham Cancer Center

"These data lend support to the recommendation that people with colorectal cancer should continue to exercise regularly, achieve and maintain a healthy body weight, and adopt a healthy diet that does not promote high levels of insulin."

"Measures such as these can reduce the risk of colorectal cancer recurrence and death."

Source: American Society of Clinical Oncology