Elevations in novel inflammatory marker predict who may benefit from preventive treatment
The reduced risk of colorectal cancer associated with taking aspirin
or other nonsteroidal anti-inflammatory drugs (NSAIDs) may be confined
to individuals already at risk because of elevations in a particular
inflammatory factor in the blood.
In a report in the March issue of Gastroenterology,
investigators from Dana-Farber Cancer Institute and Massachusetts
General Hospital (MGH) report finding that higher baseline levels of a
novel inflammatory marker indicated increased risk of developing
colorectal tumors and also predicted who might benefit from taking
aspirin or NSAIDs.
"These findings suggest that a blood biomarker may be helpful in
deciding whether individuals should take aspirin or NSAIDs to reduce
their cancer risk," says Andrew Chan, MD, MPH, of the MGH
Gastrointestinal Unit, the paper's lead author. "They also indicate
that chronic inflammatory pathways are quite complex and further studies
are needed to understand which facets of the inflammatory response are
most associated with the development of colorectal cancer."
In recent years, considerable research has supported the importance
of inflammation in the development of chronic conditions such as
cardiovascular disease and several forms of cancer. Many studies have
found reduced incidence of colorectal cancer among individuals who
regularly take aspirin or other NSAIDs, and disorders such as colitis
and inflammatory bowel disease are known to increase the risk.
To investigate whether moderately elevated levels of chronic
inflammation also raise the risk of colorectal cancer, the investigators
analyzed data from the Nurses Health Study (NHS), which has followed
more than 120,000 female registered nurses since 1976, gathering
comprehensive health information from its participants every two years.
The current study analyzed data from NHS participants who had
provided a blood sample in 1989 or 1990 and were cancer-free at that
time. After identifying 280 participants who developed colorectal
cancer during the subsequent 14 years and 555 age-matched controls who
did not, the research team analyzed their baseline levels of three
inflammatory factors — C-reactive protein (CRP), interleukin-6 (IL-6)
and soluble tumor necrosis factor receptor-2 (sTNFR-2).
Although no association was seen between levels of CRP or IL-6 and
risk of developing colorectal cancer, participants with the highest
levels of sTNFR-2 had a 60 percent greater risk than did those with the
lowest levels of the factor. In addition, the reduced risk of
developing colorectal tumors associated with regularly taking aspirin or
NSAIDs was primarily seen among participants with high baseline sTNFR-2
"Our results suggest that, even though chronic inflammation may
increase colorectal cancer risk, not all blood markers of inflammation
are markers of that risk," says Chan. "The most common blood biomarkers
of inflammation — CRP and IL-6 — do not appear to be relevant, while
sTNFR-2 does. A better understanding of the significance of these
markers will help us identify individuals most likely to benefit from
chemoprevention using aspirin or NSAIDs."
Charles Fuchs, MD, MPH,
of Dana-Farber, the study's senior author adds: "Understanding the
specific inflammatory pathways that influence risk for colorectal cancer
will be critical. While there is widespread agreement that inflammation
is broadly related to cancer risk, some pathways may be protective
while others are detrimental. More clearly defining the relevant
pathways should help us better tailor therapies and interventions that
will reduce cancer risk."
Fuchs is a professor and Chan an assistant professor of Medicine at Harvard Medical School. Additional co-authors of the Gastroenterology
paper are Shuji Ogino, MD, PhD, and Edward Giovannucci, DSc, MD,
Brigham and Women's Hospital. The study was supported by grants from
the National Institutes of Health and the Damon Runyon Cancer Research