Reduced Risk Of Colorectal Cancer Research Articles

Watermelon Powder Supplementation Reduces Colonic Cell Proliferation by Upregulating p21Waf1/Cip1 Expression

Abstract Objectives Watermelon is high in L-citrulline, a precursor for L-arginine, which in turn may reduce the risk of colorectal cancer (CRC). Research has shown that L-arginine inhibits the hyperproliferation of colorectal tumor cells as a marker for CRC. The objective of this study was, therefore, to examine the effects of watermelon powder supplementation on colonic cell proliferation and their gene expression. The hypothesis was that watermelon powder supplementation would reduce CRC risk by regulating colonic expression of genes related to epithelial cell proliferation. Methods Thirty-two 21-day-old, male, Sprague Dawley rats were randomly assigned to one of the following isocaloric diets: 0.5% watermelon powder, 0.36% L-arginine, and control for 9 weeks. All animals were injected with azoxymethane (15 mg/kg body weight). Colonic cell proliferation was measured using ki-67 immunohistochemistry, and colonic gene expression was determined using a quantitative real-time polymerase chain reaction (PCR). Results Both watermelon powder and L-arginine groups exhibited lower proliferating index (P = 0.041) and lower proliferative zone (P = 0.041). In addition, watermelon powder and L-arginine supplementation upregulated p21Waf1/Cip1 gene expression (P = 0.048). There were no significant differences in the expression of Cyclin D1, Cyclin-dependent kinase 2 (CDK2), Cyclin-dependent kinase 4 (CDK4), and Peroxisome proliferator-activated receptor γ (PPARγ). Conclusions These results suggest that watermelon or L-arginine supplementation may decrease the risk of CRC as they both reduced proliferation by upregulating a cyclin-dependent kinase inhibitor. Additional markers for gene expression involving cell proliferation are needed to confirm the present findings. Funding Sources National Watermelon Promotion Board (NWPB 15–16) National Cancer Institutes of Health (U54CA132384 for SDSU and U54132379 for UCSD).

The Role of the Gut Microbiome in Colorectal Cancer Development and Therapy Response

Colorectal cancer (CRC) is the third most common cancer worldwide and the leading cause of cancer-related deaths. Recently, several studies have demonstrated that gut microbiota can alter CRC susceptibility and progression by modulating mechanisms such as inflammation and DNA damage, and by producing metabolites involved in tumor progression or suppression. Dysbiosis of gut microbiota has been observed in patients with CRC, with a decrease in commensal bacterial species (butyrate-producing bacteria) and an enrichment of detrimental bacterial populations (pro-inflammatory opportunistic pathogens). CRC is characterized by altered production of bacterial metabolites directly involved in cancer metabolism including short-chain fatty acids and polyamines. Emerging evidence suggests that diet has an important impact on the risk of CRC development. The intake of high-fiber diets and the supplementation of diet with polyunsaturated fatty acids, polyphenols and probiotics, which are known to regulate gut microbiota, could be not only a potential mechanism for the reduction of CRC risk in a primary prevention setting, but may also be important to enhance the response to cancer therapy when used as adjuvant to conventional treatment for CRC. Therefore, a personalized modulation of the pattern of gut microbiome by diet may be a promising approach to prevent the development and progression of CRC and to improve the efficacy of antitumoral therapy.

Postmenopausal Hormone Therapy and Colorectal Cancer Risk by Molecularly Defined Subtypes and Tumor Location.

BackgroundPostmenopausal hormone therapy (HT) is associated with a decreased colorectal cancer (CRC) risk. As CRC is a heterogeneous disease, we evaluated whether the association of HT and CRC differs across etiologically relevant, molecularly defined tumor subtypes and tumor location.MethodsWe pooled data on tumor subtypes (microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, pathway: adenoma-carcinoma, alternate, serrated), tumor location (proximal colon, distal colon, rectum), and HT use among 8220 postmenopausal women (3898 CRC cases and 4322 controls) from 8 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association of ever vs never HT use with each tumor subtype compared with controls. Models were adjusted for study, age, body mass index, smoking status, and CRC family history. All statistical tests were 2-sided.ResultsAmong postmenopausal women, ever HT use was associated with a 38% reduction in overall CRC risk (OR =0.62, 95% CI = 0.56 to 0.69). This association was similar according to microsatellite instability, CpG island methylator phenotype and BRAF or KRAS status. However, the association was attenuated for tumors arising through the serrated pathway (OR = 0.81, 95% CI = 0.66 to 1.01) compared with the adenoma-carcinoma pathway (OR = 0.63, 95% CI = 0.55 to 0.73; Phet =.04) and alternate pathway (OR = 0.61, 95% CI = 0.51 to 0.72). Additionally, proximal colon tumors had a weaker association (OR = 0.71, 95% CI = 0.62 to 0.80) compared with rectal (OR = 0.54, 95% CI = 0.46 to 0.63) and distal colon (OR = 0.57, 95% CI = 0.49 to 0.66; Phet =.01) tumors.ConclusionsWe observed a strong inverse association between HT use and overall CRC risk, which may predominantly reflect a benefit of HT use for tumors arising through the adenoma-carcinoma and alternate pathways as well as distal colon and rectal tumors.

Association between the 2018 WCRF/AICR and the Low-Risk Lifestyle Scores with Colorectal Cancer Risk in the Predimed Study.

Limited longitudinal studies have been conducted to evaluate colorectal cancer (CRC) incidence based on the updated 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations or other global lifestyle indices, and none in aged populations at high cardiovascular risk. We aimed to assess the association between CRC incidence and adherence to two emerging lifestyles indices (2018 WCRF/AICR score and another low-risk lifestyle (LRL) score comprising smoking status, alcohol consumption, physical activity, diet, and body mass index) in the Spanish PREvencion con DIeta MEDiterranea (PREDIMED) cohort. We studied 7216 elderly men and women at high cardiovascular risk. The 2018 WCRF/AICR and LRL scores were calculated. Multivariable Cox proportional regression models were fitted to estimate the HRs (hazard ratios) and 95% confidence intervals (CIs) for incident CRC events. During a median interquartile range (IQR) follow-up of 6.0 (4.4–7.3) years, 97 CRC events were considered. A significant linear association was observed between each 1-point increment in the WCRF/AICR score (score range from 0 to 7) and CRC risk (HR (95% CI) = 0.79 (0.63–0.99)). Similarly, each 1-point increment in the LRL score (score range from 0 to 5) was associated with a 22% reduction in CRC risk (0.78 (0.64–0.96)). Adhering to emergent lifestyle scores might substantially reduce CRC incidence in elderly individuals. Further longitudinal studies, which take different lifestyle indexes into account, are warranted in the future.

SNP rs12982687 affects binding capacity of lncRNA UCA1 with miR-873-5p: involvement in smoking-triggered colorectal cancer progression

BackgroundThis investigation was arranged to elucidate whether single nucleotide polymorphisms (SNPs) of lncRNA UCA1 was implicated in elevating colorectal cancer (CRC) risk by interacting with environmental exposures.MethodsLncRNASNP database was firstly adopted to predict SNPs that possibly affected binding of UCA1 with miRNAs and then the interactive effect of SNPs and environmental exposure on CRC risk was evaluated by recurring to type 2 gene-environment interactions (GEI) model. Besides, MTT assay, colony formation assay, transwell assay and wound healing assay were performed to assess the activity of CRC cell lines which carried distinct genotypes of specific SNPs. The impact of nicotine on activity of CRC cells was also appraised.ResultsSNP rs12982687 of UCA1 intervened in the binding capacity of UCA1 with several miRNAs, especially miR-873-5p. MiRNAs regulated by UCA1, as predicted by mirPath software, shared genes that were enriched in HIF1 signaling pathway. Moreover, homozygote TT of rs12982687 reduced CRC risk among smokers, and CRC cells that carried rs12982687 (CC) displayed strong migration and invasion. By contrast, miR-873-5p mimic, which reduced UCA1 expression, delayed metastasis of CRC cells (all P < 0.05). Additionally, nicotine not merely elevated UCA1 and HIF-1α expressions in CRC cells, but also facilitated proliferation and metastasis of CRC cells (P < 0.05).ConclusionsSNP rs12982687 was involved in smoking-triggered CRC progression, given its influence on UCA1's binding with miR-873-5p and HIF-1 signaling.

The correlation between IL-4 polymorphisms and colorectal cancer risk in a population in Northwest China

Our aim was to investigate whether polymorphisms in the interleukin-4 (IL-4) gene are associated with the risk of colorectal cancer (CRC) in a Chinese Han population. Six single-nucleotide polymorphisms (SNPs) in the IL-4 were genotyped by Agena MassARRAY in 248 CRC patients and 463 healthy controls. The association of IL-4 polymorphisms with CRC risk was assessed by genetic models, linkage disequilibrium, and haplotype analyses. The results suggested that the CC genotype of rs2243250 confers a lower risk of CRC in the recessive model [odds ratio (OR) = 0.42, 95% confidence interval (CI): 0.19-0.92, P = 0.020]. Similarly, rs2227284 GG was associated with a reduced risk of CRC in the codominant (OR = 0.18, 95% CI: 0.04-0.82, P = 0.027) and recessive (OR = 0.19, 95% CI: 0.04-0.83, P = 0.008) models adjusted for age. Our findings suggested that rs2243250 and rs2227284 in IL-4 are associated significantly with reduced CRC risk, which may facilitate the identification of CRC patients in Chinese populations.

Postmenopausal Hormone Therapy Is Primarily Associated with Reduced Risk of Colorectal Cancer Arising through the Adenoma-Carcinoma Pathway

Abstract Our goal was to evaluate whether the inverse association of postmenopausal hormone therapy (PMH) and colorectal cancer (CRC) differs by molecularly defined CRC tumor subtypes. Methods: We pooled data on tumor markers and PMH use among 8,220 post-menopausal women (3,898 CRC cases and 4,322 controls) from eight observational studies in the Genetics of Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association of ever versus never PMH use and each tumor subtype compared with controls. We defined subtypes according to microsatellite instability (MSI-high or -low/stable), CpG island methylator phenotype (CIMP positive or negative), oncogenic mutations in BRAF and KRAS, and combinations of these markers that have been linked to specific pathways (adenoma-carcinoma, serrated, alternate). Additionally, we investigated whether associations varied by tumor anatomic location (proximal colon, distal colon, rectum). All models were adjusted for study, age, body mass index, smoking status, and family history of CRC. Wald chi-square tests were used to evaluate whether the association differed by tumor-specific subtypes. Results: Ever use of PMH was associated with a 38% reduction in overall CRC risk (OR 0.62, 95% CI 0.56–0.69). In general, this association was observed regardless of individual markers for MSI, CIMP, BRAF, or KRAS status. However, when taken altogether and grouping cases by pathway, the association was attenuated for tumors arising through the serrated pathway compared with the adenoma-carcinoma pathway (OR 0.81, 95% CI 0.65–1.01; p for difference 0.046). We also observed a weaker association for tumors of the proximal colon compared with the distal colon and rectum (OR 0.71, 95% CI 0.62–0.80; p for difference 0.010). Conclusions: In this large consortium analysis, we observed a strong inverse association between PMH use and overall CRC risk. The association may predominantly reflect a benefit of PMH use for tumors arising through the adenoma-carcinoma pathway and tumors of the distal colon and rectum, as the association was weaker for tumors arising through the serrated pathway and proximal colon tumors.

Quality indicators in colonoscopy: an evolving paradigm.

The year 1969 marked a revolution in the diagnosis of colorectal cancer (CRC). It is when Dr Wolff developed the colonoscope and quickly realized its potential in both diagnosis and treatment of colonic neoplasms. Over the past 50 years there has been exponential increase in utilization of colonoscopy with over 1 million colonoscopies performed annually throughout Australasia. Endoscopic removal of pre-malignant lesions has been proven to reduce the incidence and mortality of colorectal. Although timing and frequency of surveillance colonoscopy plays a crucial role in risk reduction of CRC, this is dependent upon the findings of the index colonoscopy. The goal of screening colonoscopy is to detect CRC and identify and remove pre-malignant neoplasms that risk progression to CRC. With increasing uptake of bowel screening throughout Australasia, there is increasing pressure to ensure all endoscopists and endoscopy units perform at a universal high-quality. All too often high demand and constant delays compromise colonoscopy quality. Without clear and concise quality indicators with transparent measurement and audit, these flaws can quickly jeopardize screening goals and patient outcomes. This review aims to explore six key quality indicators and explore the evidence behind the current recommended standards. These key indicators include; rate of adequate bowel preparation, caecal intubation rate, adenoma detection rate, withdrawal time, complication rates and surveillance intervals.

Nutritional prevention of colorectal cancer.

The preventability estimate for colorectal cancer (CRC) is approximately 50%, highlighting the huge potential for altering modifiable lifestyle factors (including diet and body fatness) in order to reduce risk of this common malignancy. There is strong evidence that dietary factors (including intake of wholegrains, fibre, red and processed meat and alcohol) affect CRC risk. The lack of positive intervention trials and limited mechanistic understanding likely explain limited public health impact of epidemiological observations, to date. An alternative strategy for nutritional prevention of CRC is use of supplements that provide higher individual nutrient exposure than obtained through the diet (chemoprevention). There are positive data for calcium and/or vitamin D and the n-3 fatty acid EPA from polyp prevention trials using colorectal adenoma as a CRC risk biomarker. Although CRC is an obesity-related malignancy, there remains a paucity of observational data supporting intentional weight loss for CRC risk reduction. Some types of obesity surgeries (Roux-en-Y gastric bypass) might actually increase subsequent CRC risk due to alteration of local intestinal factors. There is intense interest in nutritional therapy of patients after diagnosis of CRC, in order to impact on recurrence and overall survival (now often termed cancer interception). In conclusion, nutritional prevention of CRC continues to hold much promise. Increased mechanistic understanding of the role of individual nutrients (linked to intestinal microbiota), as well as a precision medicine approach to CRC chemoprevention and interception based on both tumour and host factors, should enable translation of nutritional interventions into effective CRC risk reduction measures.

Bisphosphonates Zometa and Fosamax Synergize with Metformin to Prevent AOM-Induced Colon Cancer in F344 Rat Model.

Recent observational studies suggest that bisphosphonates (BP) and antidiabetic drugs are associated with colorectal cancer risk reduction. Hence, we evaluated the colorectal cancer preventive effects of BPs (zometa and fosamax), individually and when combined with metformin, in azoxymethane-induced rat colon cancer model. Rat (30/group) were randomized and treated subcutaneously with azoxymethane to induce colorectal cancer. Dietary intervention with zometa or fosamax (0, 20, or 100 ppm) or metformin (1,000 ppm) or the combinations (zometa/fosamax 20 ppm plus metformin 1,000 ppm) began 4 weeks after azoxymethane treatment, at premalignant lesions stage. Rats were killed 40 weeks post drug intervention to assess colorectal cancer preventive efficacy. Dietary zometa (20 ppm) inhibited noninvasive adenocarcinomas multiplicity by 37% (P < 0.03) when compared with control diet fed group. Fosamax at 20 ppm and 100 ppm significantly reduced adenocarcinoma incidence (P < 0.005) and inhibited the noninvasive adenocarcinoma multiplicities by 43.8% (P < 0.009) and 60.8% (P < 0.004), respectively, compared with the group fed control diet. At 1,000 ppm dose, metformin failed to suppress colon adenocarcinoma formation. However, the lower dose combinations of zometa or fosamax with metformin resulted in significant inhibition of noninvasive adenocarcinoma by 48% (P < 0.006) and 64% (P < 0.0002), and invasive adenocarcinoma by 49% (P < 0.0005) and 38% (P < 0.006), respectively. Biomarker analysis of combination drug-treated tumors showed a decrease in cell proliferation with increased apoptosis when compared with untreated tumors. Overall, our results suggest that the combination of low doses of zometa or fosamax with metformin showed synergistic effect and significantly inhibited colon adenocarcinoma incidence and multiplicity.

Long-term colorectal cancer incidence after adenoma removal and the effects of surveillance on incidence: a multicentre, retrospective, cohort study

ObjectivePostpolypectomy colonoscopy surveillance aims to prevent colorectal cancer (CRC). The 2002 UK surveillance guidelines define low-risk, intermediate-risk and high-risk groups, recommending different strategies for each. Evidence supporting the guidelines is...

Aspirin for prevention of colorectal cancer in the elderly: friend or foe?

Cancer is the leading cause of death among men and women aged 60-79 years. Colorectal cancer is the third most common cancer in males and the second most common in females, with about 0.8 million deaths worldwide per year. Individuals older than 50 years account for 20-50% of colonic adenomas. Several measures have been proposed to decrease colorectal cancer risks, such as an increase in dietary fiber, use of aspirin, and physical activity. Nonsteroidal anti-inflammatory drugs have been proposed as protective agents against the development of colorectal cancer and colorectal adenomas. Aspirin was the first pharmacological agent endorsed by the United States Preventive Services Task Force screening for colorectal cancer chemoprevention. Although studies have shown up to 40% colorectal cancer risk reduction in individuals at average risk, data regarding this benefit are inconsistent. Several recent studies show that prophylactic use of aspirin in elderly subjects may not be beneficial in preventing the occurrence of colorectal cancers. Given the risks associated with aspirin, such as non-fatal and fatal bleeding events, aspirin’s role should be redefined, especially in individuals at risk of bleeding. This review provides a discussion of the recent studies on the role of aspirin use in elderly individuals at risk of colorectal cancer.

Higher intakes of dietary vitamin D, calcium and dairy products are inversely associated with the risk of colorectal cancer: a case-control study in China.

The effects of dietary vitamin D, Ca and dairy products intakes on colorectal cancer risk remain controversial. The present study investigated the association between these dietary intakes and the risk of colorectal cancer in Guangdong, China. From July 2010 to December 2018, 2380 patients with colorectal cancer and 2389 sex- and age-matched controls were recruited. Dietary intake data were collected through face-to-face interviews using a validated FFQ. Unconditional multivariable logistic regression models were used to calculate the OR and 95 % CI after adjusting for various confounders. Higher dietary vitamin D and Ca intakes were associated with 43 and 52 % reductions in colorectal cancer risk, with OR of 0·57 (95 % CI 0·46, 0·70) and 0·48 (95 % CI 0·39, 0·61), respectively, for the highest quartile (v. the lowest quartile) intakes. A statistically significant inverse association was observed between total dairy product intake and colorectal cancer risk, with an adjusted OR of 0·32 (95 % CI 0·27, 0·39) for the highest v. the lowest tertile. Subjects who drank milk had a 48 % lower risk of colorectal cancer than those who did not (OR 0·52, 95 % CI 0·45, 0·59). The inverse associations of dietary vitamin D, Ca, total dairy products and milk intakes with the risk of colorectal cancer were independent of sex and cancer site. Our study supports the protective effects of high dietary vitamin D, Ca and dairy products intakes against colorectal cancer in a Chinese population.

Metformin Is Associated With Reduced Odds for Colorectal Cancer Among Persons With Diabetes.

INTRODUCTION:Metformin may be associated with reduced colorectal cancer (CRC) risk, but findings from previous studies have been inconsistent and had insufficient sample sizes to examine whether the association differs by anatomic site. This study examined whether metformin was associated with reduced CRC risk, both overall and stratified by anatomic site, in a large sample of persons with diabetes who underwent colonoscopy.METHODS:We performed a case-control study of US Veterans with prevalent diabetes who underwent colonoscopy between 1999 and 2014 using Department of Veterans Affairs electronic health record data. Cases were defined by presence of CRC at colonoscopy, while controls had normal colonoscopy. The primary exposure was metformin use at time of colonoscopy (yes/no). Association of metformin exposure with CRC (further stratified by proximal, distal, or rectal subsite) was examined using multivariable and multinomial logistic regression and summarized by odds ratios (ORs) with 95% confidence intervals (CIs).RESULTS:We included 6,650 CRC patients and 454,507 normal colonoscopy patients. CRC cases were older and had lower metformin exposure. Metformin was associated with 8% relative reduction in CRC odds (OR: 0.92, 95% CI: 0.87–0.96). By subsite, metformin was associated with a 14% statistically significant reduced rectal cancer odds (OR: 0.86, 95% CI: 0.78–0.94) but no reduced distal or proximal cancer odds.DISCUSSION:Metformin was associated with reduced CRC odds—particularly rectal cancer—in a large sample of persons with diabetes undergoing colonoscopy.

Fiber, Fat, and Colorectal Cancer: New Insight into Modifiable Dietary Risk Factors.

To review recent data on the role and interactions of fiber and fat as dietary risk factors associated with colorectal cancer (CRC) risk in humans. Fiber intake shows convincing and linear dose-response negative correlation with CRC risk. Dietary fiber stimulates butyrogenic activity of the gut microbiota, providing high amounts of butyrate that shows extensive anti-neoplastic effects. A high-fat diet promotes CRC risk through stimulated bile acid metabolism, facilitating bile acid conversion by the gut microbiota to tumor-promoting deoxycholic acid. Comprehensive interactions of these microbial metabolites are likely to underlie mechanisms driving diet-dependent CRC risk in different populations, but require further experimental investigation. Dietary fiber and fat shape the composition and metabolic function of the gut microbiota, resulting in altered amounts of butyrate and deoxycholic acid in the colon. Fiber supplementation and restriction of fat intake represent promising strategies to reduce CRC risk in healthy individuals.

Development of a colorectal cancer diagnostic model and dietary risk assessment through gut microbiome analysis

Colorectal cancer (CRC) is the third most common form of cancer and poses a critical public health threat due to the global spread of westernized diets high in meat, cholesterol, and fat. Although the link between diet and colorectal cancer has been well established, the mediating role of the gut microbiota remains elusive. In this study, we sought to elucidate the connection between the gut microbiota, diet, and CRC through metagenomic analysis of bacteria isolated from the stool of CRC (n = 89) and healthy (n = 161) subjects. This analysis yielded a dozen genera that were significantly altered in CRC patients, including increased Bacteroides, Fusobacterium, Dorea, and Porphyromonas prevalence and diminished Pseudomonas, Prevotella, Acinetobacter, and Catenibacterium carriage. Based on these altered genera, we developed two novel CRC diagnostic models through stepwise selection and a simplified model using two increased and two decreased genera. As both models yielded strong AUC values above 0.8, the simplified model was applied to assess diet-based CRC risk in mice. Mice fed a westernized high-fat diet (HFD) showed greater CRC risk than mice fed a regular chow diet. Furthermore, we found that nonglutinous rice, glutinous rice, and sorghum consumption reduced CRC risk in HFD-fed mice. Collectively, these findings support the critical mediating role of the gut microbiota in diet-induced CRC risk as well as the potential of dietary grain intake to reduce microbiota-associated CRC risk. Further study is required to validate the diagnostic prediction models developed in this study as well as the preventive potential of grain consumption to reduce CRC risk.

340 High Total Cholesterol Level Increases Risk of Finding Pre-Cancerous Colonic Polyps on Initial Colonoscopies

INTRODUCTION: The association of dyslipidemia with colorectal cancer (CRC) and pre-cancerous (PC) colon polyps has been studied with mixed results. Some studies show that high total cholesterol levels reduce the risk of PC colon polyps. A recent study showed that cholesterol influences stem cell growth in the intestines, accelerating tumor formation. We examined the association of lipid levels and statin use with PC polyp detection on initial colonoscopies. METHODS: Data were collected on 3,541 patients admitted to Louisville Veterans Affairs Medical Center, and 2,629 were excluded based on specific criteria including pro-inflammatory states postulated to increase polyposis (e.g., IBD history, pre-existing malignancies) and lack of recent lipid panel data. Of 912 patients included, 313 (34%) had high total cholesterol levels (&gt;200 mg/dL) and 369 (40%) had history of statin use. Median age was 61, 89% patients were male, and 22% were African American. Data were gathered by retrospective chart review of the patient’s active medications and lipid levels (within 6 months) at the time of initial colonoscopy. Statin use was further stratified by duration and intensity. A Poisson Regression Model was used for analysis with upper and lower bounds, and rate ratios (RR) with corresponding P-values were calculated. Statistical significance was set at P &lt; 0.05. Age, sex, race, smoking history and NSAID use were controlled for. RESULTS: Our study indicates that high total cholesterol levels may be associated with increased PC polyp rates. High total cholesterol level (&gt;200 mg/dL) was associated with a 21% increase in risk of PC polyps (n = 313, RR = 1.21, P = 0.024), irrespective of statin use. Statin use in “intensity-years” (intensity multiplied by years of use) did not increase PC polyp risk, and results were statistically insignificant (n = 369, RR = 1.01, P = 0.12). Other lipid levels did not reveal statistically significant differences in PC polyp risk. CONCLUSION: Despite conflicting results of earlier studies, our study shows that high total cholesterol level may be associated with increased risk of PC polyps, irrespective of statin use. Possible mechanisms include growth of intestinal stem cells, oxidative stress, colonic inflammation, and diet associated with increased total cholesterol levels. Larger studies are needed to confirm these findings, which may have future clinical implications regarding the introduction of specific diet and lipid modification strategies to reduce CRC risk.

Mendelian randomization analysis rules out disylipidaemia as colorectal cancer cause

Dyslipidemia and statin use have been associated with colorectal cancer (CRC), but prospective studies have shown mixed results. We aimed to determine whether dyslipidemia is causally linked to CRC risk using a Mendelian randomization approach and to explore the association of statins with CRC. A case-control study was performed including 1336 CRC cases and 2744 controls (MCC-Spain). Subjects were administered an epidemiological questionnaire and were genotyped with an array which included polymorphisms associated with blood lipids levels, selected to avoid pleiotropy. Four genetic lipid scores specific for triglycerides (TG), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), or total cholesterol (TC) were created as the count of risk alleles. The genetic lipid scores were not associated with CRC. The ORs per 10 risk alleles, were for TG 0.91 (95%CI: 0.72–1.16, p = 0.44), for HDL 1.14 (95%CI: 0.95–1.37, p = 0.16), for LDL 0.97 (95%CI: 0.81–1.16, p = 0.73), and for TC 0.98 (95%CI: 0.84–1.17, p = 0.88). The LDL and TC genetic risk scores were associated with statin use, but not the HDL or TG. Statin use, overall, was a non-significant protective factor for CRC (OR 0.84; 95%CI: 0.70–1.01, p = 0.060), but lipophilic statins were associated with a CRC risk reduction (OR 0.78; 95%CI 0.66–0.96, p = 0.018). Using the Mendelian randomization approach, our study does not support the hypothesis that lipid levels are associated with the risk of CRC. This study does not rule out, however, a possible protective effect of statins in CRC by a mechanism unrelated to lipid levels.

The effect of low-dose aspirin on colorectal cancer prevention and gastrointestinal bleeding according to bodyweight and body mass index: Analysis of UK primary care data

BackgroundMeta-analysis of trial data suggests that in primary cardiovascular disease (CVD) prevention bodyweight modifies low-dose aspirin's effects on colorectal cancer (CRC) and major bleeding risk. We sought to investigate whether these effects are seen in patients with or without CVD in routine clinical practice by undertaking sub-analyses of data from two cohort studies with nested-case-control analyses. MethodsWe followed ~200,000 new users of low-dose aspirin (75–300 mg/day) and a matched cohort of non-users to identify incident cases of CRC/upper gastrointestinal bleeding (UGIB). Adjusted relative risks (RRs) with 95% confidence intervals (CIs) were calculated for current vs. non-use of low-dose aspirin using logistic regression stratified by bodyweight/body mass index (BMI) strata. ResultsRRs (95% CIs) for CRC by bodyweight were: 0.60 (0.50–0.72) for ≤70 kg, 0.68 (0.60–0.76) for >70 kg; and by BMI were 0.60 (0.52–0.68) for ≤28 kg/m2, 0.76 (0.64–0.89) for >28 kg/m2. For UGIB, estimates were: 1.49 (1.28–1.74) for ≤90 kg, 1.78 (1.29–2.45) for >90 kg/m2, 1.44 (1.21–1.72) for ≤28 kg/m2, 1.72 (1.38–2.16) for >28 kg/m2. Results were similar in the primary CVD prevention population. ConclusionOur findings suggest that the effects of low-dose aspirin in reducing CRC risk and increasing UGIB risk are not modified by bodyweight/BMI.

Design and baseline characteristics of the Biomarkers Of Risk In Colorectal Cancer (BORICC) Follow-Up study: A 12+ years follow-up.

Colorectal cancer (CRC) is the third most common cancer worldwide. Age is the strongest non-modifiable risk factor but it is estimated that over half of CRC cases are linked with lifestyle factors such as diet. The Biomarkers Of RIsk of Colorectal Cancer (BORICC) Study recruited 363 participants in 2005 to investigate the effects of lifestyle factors on biomarkers of CRC risk. In the present BORICC Follow-Up (BFU) Study, we are using a longitudinal study design to investigate the effects of ageing (12+ years) and lifestyle factors on biomarkers of CRC risk and on healthy ageing. BFU Study participants attended a study visit at North Tyneside General Hospital (UK) for collection of biological samples, including blood and rectal biopsies, and information collected included anthropometric measurements, a Health & Medications Questionnaire, physical activity and sedentary behaviour, and habitual diet. Furthermore, musculoskeletal function was assessed by heel bone densitometry, timed up and go and hand grip strength as markers of healthy ageing. The BFU Study outcomes will be similar to those measured at baseline in the BORICC Study, such as DNA methylation and mitochondrial function, with additional measurements including the gut microbiome, faecal short-chain fatty acid concentrations and expression of genes associated with CRC. Participants' recruitment to BFU Study and all sample and data collection have been completed. Forty-seven of the original BORICC participants were re-recruited to the BFU Study (mean age 67 years, 51% female). The recruits included 37 initially healthy participants and 10 participants who had adenomatous polyps at baseline. Approximately 70% of participants were over-weight or obese. Ultimately, identifying lifestyle factors that can reduce CRC risk, and understanding the underlying mechanisms for the effects of lifestyle and ageing on CRC risk, could lead to early prevention strategies.