Protein biomarker associated with improved survival in colorectal cancer

Morikowa T. JAMA. 2011;305:1685-1694.

Issue: June 10, 2011

Activation of the protein biomarker CTNNB1 was associated with better colorectal cancer-specific survival and OS for obese patients with colorectal cancer.

Researchers reviewed data collected in the Nurses’ Health Study and the Health Professionals Follow-up Study on 955 patients with any stage colon or rectal cancer. Roughly 80% of patients had normal BMI, whereas 18.7% had a BMI of at least 30.

Half of the total cohort was positive for CTNNB1, including 20.6% of obese patients. Of the patients negative for CTNNB1, 16.7% were obese.

There were 440 deaths in 141 months of follow-up, including 266 deaths from colorectal cancer.

Obese patients positive for nuclear CTNNB1 (n=70) had significantly superior cancer-specific mortality (HR=0.24; 95% CI, 0.12-0.49) and OS (HR=0.56, 95% CI, 0.35-0.90). Researchers also observed a similar but weaker positive effect of BMI using cytoplasmic CTNNB1 or membrane status.

Positive status for nuclear CTNNB1 was not significantly associated with cancer-specific survival for non-obese patients.

Five-year OS also favored positive nuclear CTNNB1, 77% vs. 74% (HR=0.98; 95% CI, 0.79-1.22), on stage-matched multivariate analysis.

Researchers found that a high-rate of post-diagnosis physical activity, defined as at least 18 metabolic equivalent task hours per week, improved colorectal cancer-specific survival in patients with negative nuclear CTNNB1 (HR=0.33; 95% CI, 0.13-0.81). Physical activity was not associated with improved disease-specific survival (HR=1.07; 95% CI, 0.50-2.30) or OS (HR=0.86; 95% CI, 0.55-1.34) for patients positive for CTNNB1.

Beta-catenin is a marker that's been evaluated in several other studies; none have shown a correlation between expression and outcome, and some have shown a negative correlation between nuclear expression and outcome. This is an interesting study, but it's hypothesis-generating at this point, rather than confirmatory or practice changing. The study is important because it's one of the few studies to look at a marker and its interaction between a modifiable patient characteristic. However, there is no good hypothesis generated in the study to explain why patients with a high BMI benefit from nuclear expression of beta-catenin, so it's not clear whether further studies would confirm this finding. It's not clear to me why patients who are overweight would benefit from a higher level of nuclear beta-catenin.

– Marwan Fakih, MD
Chief of the gastrointestinal section,
Roswell Park Cancer Institute, Buffalo, NY.

Disclosure: Dr. Fakih reported no relevant financial interests.

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