CTNNB1 link to colorectal cancer survival modified by body mass index and exercise
MedWire News: Patients with colorectal cancer may show differential improvement with exercise depending on their cadherin-associated protein beta (CTNNB)1 status, suggest study findings.
The results are of clinical importance as they provide evidence for a possible interactive effect of tumor CTNNB1 signaling and patients' energy balance status in determining tumor cell behavior.
"Our data support the hypothesis that progression of a tumor with an inactive WNT-CTNNB1 signaling pathway might be influenced by energy intake and expenditure, whereas a tumor with an active WNT-CTNNB1 signaling pathway might progress independent of energy balance status," say Shuji Ogino (Harvard Medical School, Boston, Massachusetts, USA) and co-authors.
Using data from the Nurses' Health Study and the Health Professionals Follow-up Study, the researchers evaluated CTNNB1 localization by immunohistochemistry in 955 patients with stage I, II, III, or IV colon and rectal cancer from 1980 to 2004. Prognostic associations of body mass index and level of post-diagnosis physical activity with CTNNB1 status were then investigated, adjusting for clinical and tumor features.
Obese patients (BMI ≥30 kg/m2) who were positive for nuclear CTNNB1 showed significantly better 5-year colorectal cancer-specific survival and overall survival compared with those with negative status (adjusted hazard ratio (aHR)=0.24 and 0.56, respectively).
However, positive status for nuclear CTNNB1 was not significantly associated with colorectal cancer-specific survival or overall survival in non-obese patients.
The study also found that a high level of physical activity (≥18 hours of metabolic equivalent tasks [MET]/week) post-diagnosis was associated with significantly improved 5-year colorectal cancer-specific survival in patients negative for CTNNB1 and cancer in stages I, II, or III (aHR=0.33 compared with patients engaging in <18 MET-hours/week). Among patients with a positive CTNNB1 status, however, there was no significant association between physical activity and survival.
The researchers say the findings suggest that "the effects of alterations in the WNT-CTNNB1 pathway on outcome are modified by BMI and physical activity."
Writing in JAMA, Ogino et al conclude: "Although our data need to be confirmed by independent data sets, tumor CTNNB1 status may serve as a predictive biomarker for response to a prescription for physical activity in clinical practice. Because physical activity is a modifiable lifestyle factor, our data may have considerable clinical implications."
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By Ingrid Grasmo