IMAGING-BASED VISCERAL ADIPOSE TISSUE VOLUME (VAT) AND CANCER RISK IN THE UK BIOBANK COHORT

Background: Diets high in animal fat and low in plant fiber increase colorectal cancer (CRC) risk, while diets high in fiber, but low in animal fat, are protective. Bacteria present in the colon produce beneficial and harmful metabolites from our diets. Fiber is fermented by these bacteria, producing short-chain fatty acids (SCFA). One of them, butyric acid, is the major energy source for colonic cells and has strong anti-inflammatory/anti-carcinogenic properties. Excess consumption of animal fats is known to increase levels of carcinogenic secondary bile acids in the colon, namely lithocholic acid (LCA) and deoxycholic acid (DCA). Alaska Native (AN) people, at highest risk globally for CRC, were interested in whether increasing dietary fiber intake could reduce CRC risk, as their diets are high in meat and fat, but deficient in fiber.
Purpose: Evaluate whether a fiber supplement added to the usual diet of AN volunteers will increase the microbial production of butyrate and suppress fecal bile acids, thus reducing CRC risk.
Methods: Forty-eight healthy AN adult volunteers were enrolled a 4-week randomized, double-blind, placebo-controlled trial in which they received either a resistant starch supplement, RS, a non-chemically modified food starch extracted from high amylose corn, or a digestible starch supplement, DS, an isocaloric amylopectin supplement, occurring naturally as a branched glucose polymer. Quantitation of fecal SCFA and bile acids was performed by on stool samples collected pre- and post-supplementation by gas chromatography-flame-ionization detection (GC-FID) and gas chromatography-mass spectrometry (GC-MS) (Figure 1). The primary endpoint was to evaluate whether RS could suppress epithelial proliferation measured by immunohistological staining of proliferative cells with Ki67 in well orientated crypts. The magnitude of the Ki67 suppression was also used to define clinically significant responses of <20%, termed “responders” (Figure 2). Statistical analyses were performed with paired t-tests on all SCFA and bile acids.
Results: Butyrate levels showed increases in both groups, significant in the RS group. Conversely, there were reductions in LCA and DCA in both groups, significant for DCA in the RS group.
Conclusions: RS significantly increased fecal anticarcinogenic butyrate and suppressed inflammatory and potentially carcinogenic secondary bile acids which might explain the suppression of cancer biomarkers in the colonic mucosa. Interestingly, DS had similar but less pronounced effects. It is noteworthy that previous dietary analysis indicated the AN diet was also low in carbohydrate (Ocvirk et al. AJCN 2016) and so it is possible that their diet could be improved by the increased consumption of all forms of complex carbohydrate.
Acknowledgements: NIH grant R01 CA204403

Background: Obesity, particularly abdominal obesity, is a major risk factor of cancer. However, it remains unknown how visceral fat may influence cancer risk independently of traditional measures of overall and abdominal obesity, due to the lack of large-scale data on visceral fat. Methods: Leveraging the body (abdominal) magnetic resonance imaging (MRI) measurements among 23,148 participants who attended the first imaging test since 2014 in the UK Biobank (UKB) cohort, we prospectively examined visceral adipose tissue volume (VAT) in relation to the risk of overall, obesity-related, and gastrointestinal (GI) cancer and major individual cancers in men and women, using multivariable Cox proportional hazards regression (see the table 1 footnote for the covariate list). We also trained and validated a prediction equation for VAT based on demographic factors and traditional anthropometric measures (see the predictor list and brief summary of process in the table footnote). We compared the association of the measured and predicted VAT with cancer risk among individuals with the MRI data, and then assessed the predicted VAT in relation to cancer risk among 471,089 participants in the overall UKB cohort who attended the initial assessment visit (2006-2010). To examine the added value of VAT beyond traditional measures of overall and abdominal obesity, we conducted a joint association analysis for predicted VAT with body mass index (BMI) and waist circumference (WC) in relation to total cancer risk in the overall UKB cohort. Results: In the MRI subcohort and overall UKB cohort, respectively, we documented 719 and 47,940 cancer cases during a median follow-up of 4 and 12 years. In the MRI subcohort, each unit (90^th to 10^th difference) increase in the measured VAT was associated with 33% and 74% higher risk of total cancer in men (multivariable HR=1.33, 95% CI: 1.05-1.67) and women (1.74, 1.11-2.72), respectively. The final equation for predicted VAT showed a similarly high R² in the training (0.76) and validation (0.74) sets; no difference was found between the measured and predicted VAT in the validation set (p-value>0.05), with Spearman correlation (r=0.87). In the MRI subcohort, the predicted VAT showed similar HRs to those of the measured VAT. After applying the prediction equation to the overall UKB cohort, we found that the predicted VAT was associated with higher risk of total cancer and many individual cancers, particularly GI, kidney, liver, and endometrial cancers. Furthermore, within each of the BMI and WC groups, predicted VAT was associated with a higher risk of total cancer. Conclusions: VAT was associated with an increased risk of total cancer and several individual cancers. VAT also provided additional information regarding total cancer risks within each of the BMI or WC groups.