Adult-Attained Height and Colorectal Cancer Risk: A Cohort Study, Systematic Review, and Meta-Analysis.

BACKGROUND: The influence of anthropometric characteristics on colorectal neoplasia biology is unclear. We conducted a systematic review and meta-analysis to determine if adult-attained height is independently associated with the risk of colorectal cancer or adenoma. METHODS: We searched MEDLINE, EMBASE, the Cochrane Library, and Web of Science from inception to August 2020 for studies on the association between adult-attained height and colorectal cancer or adenoma. The original data from the Johns Hopkins (Baltimore, MD) Colon Biofilm study was also included. The overall HR/OR of colorectal cancer/adenoma with increased height was estimated using random-effects meta-analysis. RESULTS: We included 47 observational studies involving 280,644 colorectal cancer and 14,139 colorectal adenoma cases. Thirty-three studies reported data for colorectal cancer incidence per 10-cm increase in height; 19 yielded an HR of 1.14 [95% confidence interval (CI), 1.11-1.17; P < 0.001), and 14 engendered an OR of 1.09 (95% CI, 1.05-1.13; P < 0.001). Twenty-six studies compared colorectal cancer incidence between individuals within the highest versus the lowest height percentile; 19 indicated an HR of 1.24 (95% CI, 1.19-1.30; P < 0.001), and seven resulting in an OR of 1.07 (95% CI, 0.92-1.25; P = 0.39). Four studies reported data for assessing colorectal adenoma incidence per 10-cm increase in height, showing an overall OR of 1.06 (95% CI, 1.00-1.12; P = 0.03). CONCLUSIONS: Greater adult attained height is associated with an increased risk of colorectal cancer and adenoma. IMPACT: Height should be considered as a risk factor for colorectal cancer screening.

Self-reported Metabolic Risk Factor Associations with Adenomatous, Sessile Serrated, and Synchronous Adenomatous and Sessile Serrated Polyps.

Studies have found a positive association between metabolic risk factors, such as obesity and diabetes, and adenomatous polyps (AP). However, fewer studies have assessed the association between sessile serrated polyps (SSP) or synchronous diagnosis of APs and SSPs (synch polyps). Study participants (N = 1,370; ages 40-85) undergoing screening colonoscopy were enrolled between August 2016 and February 2020. Self-reported metabolic risk factors, including diabetes, hypertension, hyperlipidemia, and overweight/obesity, were evaluated for associations with new diagnoses of APs, SSPs, and synch polyps at the present colonoscopy. Average participant age was 60.73 ± 8.63 (SD) years; 56.7% were female and 90.9% white. In an assessment of individual metabolic risk factors, adjusted for age, sex, race, and smoking status, increased body mass index (BMI; overweight or obese vs. normal BMI of <25 kg/m2) was associated with an increased odds for new onset of colon APs (P trend < 0.001) as was a diagnosis of diabetes [adjusted conditional OR (aCOR) = 1.59 (1.10-2.29)]. No associations were seen between the metabolic risk factors and onset of SSPs. Being obese or hypertensive each increased the odds of new onset of synch polyps with aCOR values of 2.09 (1.01-4.32) and 1.79 (1.06-3.02), respectively. Self-reported risk factors may help assess polyp type risk. Because SSPs and synch polyps are rare, larger studies are needed to improve our understanding of the contribution of these factors to polyp risk. These data lead us to hypothesize that differences in observed metabolic risk factors between polyp types reflect select metabolic impact on pathways to colorectal cancer. PREVENTION RELEVANCE: Self-reported medical history provides valuable insight into polyp risk, potentially enabling the use of larger retrospective studies of colonoscopy populations to assess knowledge gaps. More aggressive colonoscopy screening, critical to colorectal cancer prevention, may be considered in populations of individuals with metabolic risk factors and modifiable lifestyle risk factors.

Yogurt consumption and colorectal polyps.

Diet modifies the risk of colorectal cancer (CRC), and inconclusive evidence suggests that yogurt may protect against CRC. We analysed the data collected from two separate colonoscopy-based case-control studies. The Tennessee Colorectal Polyp Study (TCPS) and Johns Hopkins Biofilm Study included 5446 and 1061 participants, respectively, diagnosed with hyperplastic polyp (HP), sessile serrated polyp, adenomatous polyp (AP) or without any polyps. Multinomial logistic regression models were used to derive OR and 95 % CI to evaluate comparisons between cases and polyp-free controls and case-case comparisons between different polyp types. We evaluated the association between frequency of yogurt intake and probiotic use with the diagnosis of colorectal polyps. In the TCPS, daily yogurt intake v. no/rare intake was associated with decreased odds of HP (OR 0·54; 95 % CI 0·31, 0·95) and weekly yogurt intake was associated with decreased odds of AP among women (OR 0·73; 95 % CI 0·55, 0·98). In the Biofilm Study, both weekly yogurt intake and probiotic use were associated with a non-significant reduction in odds of overall AP (OR 0·75; 95 % CI 0·54, 1·04) and (OR 0·72; 95 % CI 0·49, 1·06) in comparison with no use, respectively. In summary, yogurt intake may be associated with decreased odds of HP and AP and probiotic use may be associated with decreased odds of AP. Further prospective studies are needed to verify these associations.

Loss of imprinting of insulin growth factor II gene: a potential heritable biomarker for colon neoplasia predisposition.

BACKGROUND & AIMS: Loss of genomic imprinting (LOI) of insulin-like growth factor II gene (IGF2) involves abnormal activation of the normally silent maternally inherited allele. LOI of IGF2 has been associated with personal and family history of colorectal neoplasia (CRN), supporting a role for LOI in colorectal carcinogenesis. Whether LOI of IGF2 is associated with known environmental risk factors for CRN is unknown. METHODS: We performed quantitative hot-stop PCR for imprinting analysis of IGF2 on normal peripheral blood lymphocytes (PBL) of individuals. Environmental exposures including tobacco, alcohol, NSAIDs, and nutrient consumption (calcium, folate, selenium, fiber, and fat) were correlated with LOI expression in PBL. Odds ratios (OR) and 95% CI were calculated. RESULTS: The prevalence of LOI of IGF2 was examined in 172 individuals. Persons with CRN (adenomas/cancer) had 5.1-fold (95% CI: 1.92-13.6) increased risk of having LOI of IGF2 in PBL compared with those without CRN. In contrast, tobacco smoking (OR = 0.96, 95% CI: 0.36-2.55), alcohol consumption (OR = 1.22, 95% CI: 0.45-3.3), and NSAIDs use (OR = 1.21, 95% CI: 0.38-3.94) were not significantly associated with LOI of IGF2. Nutrient ingestion including calcium (P = 0.61), folate (P = 0.23), selenium (P = 0.19), fiber (P = 0.63), and fat (P = 0.14) was not statistically correlated with LOI of IGF2. CONCLUSIONS: Abnormal imprinting of IGF2 gene was strongly associated with CRN but not with any of the environmental exposures examined. LOI of IGF2 does not appear to be an environmentally acquired phenomenon but rather a hereditary risk factor for CRN.

Loss of IGF2 imprinting: a potential marker of colorectal cancer risk.

Loss of imprinting (LOI), an epigenetic alteration affecting the insulin-like growth factor II gene (IGF2), is found in normal colonic mucosa of about 30% of colorectal cancer (CRC) patients, but it is found in only 10% of healthy individuals. In a pilot study to investigate the utility of LOI as a marker of CRC risk, we evaluated 172 patients at a colonoscopy clinic. The adjusted odds ratio for LOI in lymphocytes was 5.15 for patients with a positive family history [95% confidence interval (95% CI), 1.70 to 16.96; probability P = 0.002], 3.46 for patients with adenomas (95% CI, 1.14 to 11.37; P = 0.026), and 21.7 for patients with CRC (95% CI, 3.48 to 153.6; P = 0.0005). LOI can be assayed with a DNA-based blood test, and it may be a valuable predictive marker of an individual's risk for CRC.