Abstract 3854: B-catenin expression and obesity in African Americans with colorectal neoplasia: Is there a relationship
Authors: Shokrani Babak , Hydari Tahmineh , Nouraie Seyed-Mehdi , Hassan Sally , Kansal Vandana , Lee Edward , Brim Hassan , Ashktorab Hassan 
Published: May 2015

Background: Colorectal cancer (CRC) risk increases with obesity, physical inactivity, and the metabolic syndrome. Studies suggest that obesity may be associated with 30-60% greater risk of CRC. Activation of the WNT via β-catenin (CTNNB1) signaling pathway plays a critical role in colorectal carcinogenesis. Accumulating evidence indicates a negative relationship between CTNNB1 signaling and obesity.

Aim: To determine the association between obesity and CTNNB1 expression in African Americans (AA) with colorectal lesions, a population at high risk for both CRC and obesity.

Methods: We reviewed the pathology records of 152 colorectal specimens from 2010-2012 (46 CRCs, 74 advanced adenoma and 32 normal healthy colon). We prepared Tissue Microarray Array (TMA) from these samples. Immunohistochemistry (IHC) for CTNNB1 (β-catenin; clone β-Catenin-1) was performed on the constructed TMAs. The IHC results were evaluated by 2 pathologists and the nuclear intensity staining was scored from 0-4. BMI, sex, age, location of the lesion and other demographic data were obtained. Data integration and analysis were performed using Logistic regression analyses. This was applied to calculate the diagnostic odds ratio (95%CI) for each nuclear staining intensity. ROC curve was applied for diagnostic ability of β-Catenin staining percentage.

Results: Positive nuclear staining in normal, advanced adenoma and CRC was 0%, 24% and 41%, respectively (P &lt;0.001). CRCs were associated with positive status for nuclear CTNNB1 intensity (adjusted OR: 3.40, 95%CI=1.42-8.15, P=0.006 for positive nuclear staining) compared to non CRC samples (normals or advanced adenomas). Nuclear staining percentage showed a good diagnostic ability for CRC (AUC: 0.63, 95%CI=0.55-0.71). Overweight and obese patients (BMI&gt;25) did not show a significant (p=0.3) CTNNB1 nuclear expression (17% positive in normal weight vs. 27% positive in overweight/obese). Association between nuclear intensity and CRC was not different between normal and overweight patients (P for interaction = 0.6). The positive nuclear CTNNB1 status in CRC stage III and IV (43% of all CRC) was not different from stage I and II (50%. vs. 36%, respectively, P = 0.4).

Conclusion: In our study, advanced adenomas and CRCs were associated with activation of β-catenin in physically fit, overweight and obese patients and hence participation of the metabolic and WNT pathways was seen in African American patients. We did not find any statistically significant differences in β -Catenin expression between normal and overweight/obese patients in AA population. The WNT/β-catenin pathway has a potential to be used as a molecular pathology effector in colon carcinogenic transformation. Whether or not BMI is a modifier of this pathway need to be further investigated.

Citation Format: Babak Shokrani, Tahmineh Hydari, Seyed-Mehdi Nouraie, Sally Hassan, Vandana Kansal, Edward Lee, Hassan Brim, Hassan Ashktorab. B-catenin expression and obesity in African Americans with colorectal neoplasia: Is there a relationship. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3854. doi:10.1158/1538-7445.AM2014-3854