title: Prospective analysis of body mass index, physical activity, and colorectal cancer risk associated with β-catenin (CTNNB1) status.
abstract: Dysregulation of the WNT/β-catenin (CTNNB1) signaling pathway is implicated in colorectal carcinoma and metabolic diseases. Considering these roles and cancer prevention, we hypothesized that tumor CTNNB1 status might influence cellular sensitivity to obesity and physical activity. In clinical follow-up of 109,046 women in the Nurses' Health Study and 47,684 men in the Health Professionals Follow-up Study, there were 861 incident rectal and colon cancers with tissue immunohistochemistry data on nuclear CTNNB1 expression. Using this molecular pathological epidemiology database, we conducted Cox proportional hazards regression analysis using data duplication method to assess differential associations of body mass index (BMI) or exercise activity with colorectal cancer risk according to tumor CTNNB1 status. Greater BMI was associated with a significantly higher risk of CTNNB1-negative cancer [multivariate HR = 1.34; 95% confidence interval (CI), 1.18-1.53 for 5.0 kg/m(2) increment; Ptrend = 0.0001] but not with CTNNB1-positive cancer risk (multivariate HR = 1.07; 95% CI, 0.92-1.25 for 5.0 kg/m(2) increment; Ptrend = 0.36; Pheterogeneity = 0.027, between CTNNB1-negative and CTNNB1-positive cancer risks). Physical activity level was associated with a lower risk of CTNNB1-negative cancer (multivariate HR = 0.93; 95% CI, 0.87-1.00 for 10 MET-h/wk increment; Ptrend = 0.044) but not with CTNNB1-positive cancer risk (multivariate HR = 0.98; 95% CI, 0.91-1.05 for 10 MET-h/wk increment; Ptrend = 0.60). Our findings argue that obesity and physical inactivity are associated with a higher risk of CTNNB1-negative colorectal cancer but not with CTNNB1-positive cancer risk. Furthermore, they suggest that energy balance and metabolism status exerts its effect in a specific carcinogenesis pathway that is less likely dependent on WNT/CTNNB1 activation. Cancer Res; 73(5); 1600-10. ©2012 AACR.
authors: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave., Boston, MA 02215, USA.
authors: Teppei
authors: T
authors: Morikawa
authors: Aya
authors: A
authors: Kuchiba
authors: Paul
authors: P
authors: Lochhead
authors: Reiko
authors: R
authors: Nishihara
authors: Mai
authors: M
authors: Yamauchi
authors: Yu
authors: Y
authors: Imamura
authors: Xiaoyun
authors: X
authors: Liao
authors: Zhi Rong
authors: ZR
authors: Qian
authors: Kimmie
authors: K
authors: Ng
authors: Andrew T
authors: AT
authors: Chan
authors: Jeffrey A
authors: JA
authors: Meyerhardt
authors: Edward
authors: E
authors: Giovannucci
authors: Charles S
authors: CS
authors: Fuchs
authors: Shuji
authors: S
authors: Ogino
mesh_terms: D015992:Body Mass Index; D015179:Colorectal Neoplasms / Q000453:epidemiology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009043:Motor Activity; D011446:Prospective Studies; D012307:Risk Factors; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C495270:CTNNB1 protein, human; D051176:beta Catenin