Lower Risk Of Colorectal Cancer Research Articles

Association between meeting the WCRF/AICR cancer prevention recommendations and colorectal cancer incidence: results from the VITAL cohort.

In 2007, the World Cancer Research Fund (WCRF) and American Institute for Cancer Research (AICR) published eight recommendations regarding body weight, physical activity, and dietary behaviors aimed at reducing cancer incidence worldwide. In this paper, we assess whether meeting the WCRF/AICR recommendations is associated with lower colorectal cancer (CRC) incidence; evaluate whether particular recommendations are most strongly associated with lower CRC incidence; and assess whether associations differ by sex. We operationalized six of the recommendations (related to body weight, physical activity, energy density, plant foods, red and processed meat, and alcohol) and examined their association with CRC incidence over 7.6years of follow-up in the prospective VITamins And Lifestyle Study cohort. Participants included 66,920 adults aged 50-76years at baseline (2000-2002) with no history of CRC and with complete data for the recommendations evaluated. Incident colorectal cancers (n=546) were tracked through 2009. Compared with meeting no recommendations, meeting 1-3 recommendations was associated with 34-45% lower CRC incidence, and meeting 4-6 was associated with 58% lower incidence (95% CI 34%, 74%) in fully adjusted analyses. The recommendations most strongly associated with lower CRC risk for women were related to body fatness and red and processed meat, while for men these were alcohol intake and red and processed meat. Differences by sex were statistically significant (p<0.05) for the recommendations related to body weight and to alcohol. Meeting the WCRF/AICR recommendations, particularly those related to alcohol, body weight, and red and processed meat, could substantially reduce CRC incidence; however, associations differ by sex.

Genome-Wide Interaction Analyses between Genetic Variants and Alcohol Consumption and Smoking for Risk of Colorectal Cancer

Genome-wide association studies (GWAS) have identified many genetic susceptibility loci for colorectal cancer (CRC). However, variants in these loci explain only a small proportion of familial aggregation, and there are likely additional variants that are associated with CRC susceptibility. Genome-wide studies of gene-environment interactions may identify variants that are not detected in GWAS of marginal gene effects. To study this, we conducted a genome-wide analysis for interaction between genetic variants and alcohol consumption and cigarette smoking using data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Interactions were tested using logistic regression. We identified interaction between CRC risk and alcohol consumption and variants in the 9q22.32/HIATL1 (Pinteraction = 1.76×10−8; permuted p-value 3.51x10-8) region. Compared to non-/occasional drinking light to moderate alcohol consumption was associated with a lower risk of colorectal cancer among individuals with rs9409565 CT genotype (OR, 0.82 [95% CI, 0.74–0.91]; P = 2.1×10−4) and TT genotypes (OR,0.62 [95% CI, 0.51–0.75]; P = 1.3×10−6) but not associated among those with the CC genotype (p = 0.059). No genome-wide statistically significant interactions were observed for smoking. If replicated our suggestive finding of a genome-wide significant interaction between genetic variants and alcohol consumption might contribute to understanding colorectal cancer etiology and identifying subpopulations with differential susceptibility to the effect of alcohol on CRC risk.

Vegetarianism and breast, colorectal and prostate cancer risk: an overview and meta-analysis of cohort studies.

Vegetarian diets may be associated with certain benefits toward human health, although current evidence is scarce and contrasting. In the present study, a systematic review and meta-analysis of prospective cohort studies was performed with respect to the association between vegetarian diets and breast, colorectal and prostate cancer risk. Studies were systematically searched in Pubmed and EMBASE electronic databases. Eligible studies had a prospective design and compared vegetarian, semi- and pesco-vegetarian diets with a non-vegetarian diet. Random-effects models were applied to calculate relative risks (RRs) of cancer between diets. Statistical heterogeneity and publication bias were explored. A total of nine studies were included in the meta-analysis. Studies were conducted on six cohorts accounting for 686 629 individuals, and 3441, 4062 and 1935 cases of breast, colorectal and prostate cancer, respectively. None of the analyses showed a significant association of vegetarian diet and a lower risk of either breast, colorectal, and prostate cancer compared to a non-vegetarian diet. By contrast, a lower risk of colorectal cancer was associated with a semi-vegetarian diet (RR = 0.86, 95% confidence interval = 0.79-0.94; I2 = 0%, Pheterogeneity = 0.82) and a pesco-vegetarian diet (RR = 0.67, 95% confidence interval = 0.53, 0.83; I2 = 0%, Pheterogeneity = 0.46) compared to a non-vegetarian diet. The subgroup analysis by cancer localisation showed no differences in summary risk estimates between colon and rectal cancer. A summary of the existing evidence from cohort studies on vegetarian diets showed that complete exclusion of any source of protein from the diet is not associated with further benefits for human health.

Veteransʼ Attitudes Towards De-intensification of Surveillance Colonoscopy for Low-Risk Adenomas: 2016 ACG Fellows-In-Training Award (CRC Prevention Category) 2016 ACG Presidential Poster Award

Introduction: Patients with low risk adenomas (LRAs - i.e., 1-2 small tubular adenomas) are at low risk for colorectal cancer (CRC). As a result, current U.S. Multi-Society Task Force guidelines recommend a surveillance interval of up to 10 years in such patients. But endoscopists rarely recommend an interval greater than 5 years, even in those who are unlikely to benefit (e.g., those with limited life expectancy). The purpose of this study was to assess Veterans' attitudes towards de-intensification of surveillance (i.e., less frequent surveillance) for LRAs. Methods: We developed a 39-item multiple-choice, scenario-based survey to assess patient attitudes towards de-intensification of surveillance colonoscopy. Inclusion criteria were: (1) age 60-89; and, (2) LRAs on screening colonoscopy performed at a single academic VA center from 2010-2015. Patients with any other indication for colonoscopy or those at increased risk for CRC (i.e., history of CRC, inflammatory bowel disease, or a polyposis syndrome), were excluded. The primary outcome was comfort waiting 10 years (versus 5 years) for surveillance colonoscopy (measured on a 7-point unidirectional Likert-type scale). Multivariable linear regression was used to identify predictors of comfort with waiting. The survey was mailed with a $10 gift card incentive. Results: 345 of 491 surveys (70%) were returned for analysis. Respondents were predominantly white (88%) and male (98%). The median age was 68 years and 63% completed education beyond high school. Health literacy was adequate in 90%. The vast majority of respondents (85%) were interested in undergoing routine surveillance at a 5-year interval if recommended by their physician. Despite this high interest in 5-year surveillance, nearly half (45%) reported that they would also be comfortable waiting 10 years. In multivariable linear regression, trust in physician was associated with more comfort waiting 10 years. Concern about developing CRC and perceived effectiveness of screening were both associated with less comfort waiting 10 years. No other factors, including demographics, education, or health literacy, were associated with comfort waiting. Conclusion: Patients with LRAs have diverse preferences for when to undergo surveillance colonoscopy. Given the clinical uncertainty about the optimal surveillance interval in these patients, decisions about the timing of surveillance should incorporate patient preferences rather than simply enforce the preferences of endoscopists.

Exam 4: Regular Aspirin Use Associates With Lower Risk of Colorectal Cancers With Low Numbers of Tumor-Infiltrating Lymphocytes

Exam 4: Regular Aspirin Use Associates With Lower Risk of Colorectal Cancers With Low Numbers of Tumor-Infiltrating Lymphocytes

Marine ω-3 Polyunsaturated Fatty Acid Intake and Risk of Colorectal Cancer Characterized by Tumor-Infiltrating T Cells.

Marine ω-3 polyunsaturated fatty acids (PUFAs), including eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid, possess potent immunomodulatory activity and may protect against cancer development. However, evidence relating marine ω-3 PUFAs to colorectal cancer (CRC) risk remains inconclusive. To test the hypothesis that marine ω-3 PUFA intake may be associated with lower risk of CRC subsets characterized by immune infiltrate. This prospective cohort study was conducted among participants in the Nurses' Health Study (1984-2010) and Health Professionals Follow-up Study (1986-2010). Intake of marine ω-3 PUFAs. Incidence of CRC characterized by CD3+, CD8+, CD45RO (PTPRC)+, or FOXP3+ T-cell densities in tumor tissue, measured by immunohistochemical and computer-assisted image analysis. Among 173 229 predominantly white participants, 125 172 with 2 895 704 person-years of follow-up provided data about marine ω-3 PUFA intake every 4 years through a validated food frequency questionnaire and followed up for incident CRC evaluation. Of 2504 CRC cases, we documented 614 (252 men, 362 women) from which we could assess T-cell infiltration in the tumor microenvironment. The inverse association of marine ω-3 PUFAs intake with CRC risk differed according to FOXP3+ T-cell infiltration: compared with intake of less than 0.15 g/d of marine ω-3 PUFAs, intake of at least 0.35 g/d was associated with a multivariable hazard ratio (HR) of 0.57 (95% CI, 0.40-0.81; P < .001 for trend) for FOXP3+ T-cell-high tumors. In contrast, the HR for FOXP3+ T-cell-low tumors was 1.14 (95% CI, 0.8-1.60) (P = .77 for trend; P = .01 for heterogeneity). No statistically significant differential association was found for high-density tumors (compared with low-density tumors) according to CD3+, CD8+, or CD45RO+ cell density (P ≥ .34 for heterogeneity for all comparisons). In functional assays, the suppressive activity of regulatory T cells was approximately 2-fold lower (T-effector-cell proliferation, ≥64% vs 38%) when preincubated with docosahexaenoic acid at 50μM, 100μM, and 200μM concentrations than without docosahexaenoic acid (P < .001 for all comparisons). High marine ω-3 PUFA intake was associated with lower risk of CRC with high-level, but not low-level, FOXP3+ T-cell density, suggesting a potential role of ω-3 PUFAs in cancer immunoprevention through modulation of regulatory T cells.

Cribado del cáncer colorrectal

In the latest meeting of the American Gastroenterological Association, several clinical studies were presented that aimed to evaluate the various colorectal cancer screening strategies, although most assessed the various aspects of faecal immunochemical testing (FIT) and colonoscopy. Data were presented from consecutive FIT-based screening rounds, confirming the importance of adherence to consecutive screening rounds, achieving a similar or superior diagnostic yield to endoscopic studies. There was confirmation of the importance of not delaying endoscopic study after a positive result. Participants with a negative FIT (score of 0) had a low risk for colorectal cancer. Several studies seemed to confirm the importance of high-quality colonoscopy in colorectal cancer screening programmes. The implementation of high-quality colonoscopies has reduced mortality from proximal lesions and reduced interval cancers in various studies. Finally, participants with a normal colonoscopy result or with a small adenoma are at low risk for developing advanced neoplasms during follow-up.

Family history and the risk of colorectal cancer: The importance of patients' history of colonoscopy.

Registry-based studies on the risk of colorectal cancer (CRC) for persons with a family history (FH) typically did not control for important covariates, such as history of colonoscopy. We aimed to quantify the association between FH and CRC risk, carefully accounting for potential confounders. We conducted a population-based case-control study in Germany. A total of 4,313 patients with a first diagnosis of CRC (cases) and 3,153 controls recruited from 2003 to 2014 were included. We used multiple logistic regression analyses to assess the association between FH and risk of CRC with odds ratios (OR) and the resulting 95% confidence intervals (95% CI). A total of 582 cases (13.5%) and 321 (10.2%) controls reported a history of CRC in a first-degree relative, which was associated with a 41% increase in risk of CRC (OR: 1.41, 95% CI 1.22-1.63) after adjustment for sex and age. The OR substantially increased to 1.73 (95% CI, 1.48-2.03) after comprehensive adjustment including previous colonoscopies. Irrespective of their FH status, persons with history of colonoscopies had a lower CRC risk compared with persons without previous colonoscopies and without family history (OR: 0.25, 95% CI, 0.22-0.28 for persons without FH and OR 0.45, 95% CI, 0.36-0.56 for persons with FH). In an era of widespread use of colonoscopy, adjusting for previous colonoscopy is therefore crucial for deriving valid estimates of FH-related CRC risk. Colonoscopy reduces the risk of CRC among those with FH far below levels of people with no FH and no colonoscopy.

Calcium intake and colorectal cancer risk: Results from the nurses' health study and health professionals follow-up study.

The relationship between calcium intake and colorectal cancer (CRC) risk remains inconclusive. We conducted this study to evaluate whether the association between calcium intake and CRC risk differs by anatomic subsite and determine the dose-response relationship for this association, as well as assess when in carcinogenesis calcium may play a role. We assessed calcium intake every 4 years and followed 88,509 women (1980-2012) in the Nurses' Health Study and 47,740 men (1986-2012) in the Health Professionals Follow-Up Study. We documented 3,078 incident CRC cases. Total calcium intake (≥1,400 vs. <600 mg/d) was associated with a statistically significant lower risk of colon cancer (multivariable relative risk: 0.78, 95%CI: 0.65-0.95). Similar results were observed by different sources of calcium (from all foods or dairy products only). The inverse association was linear and suggestively stronger for distal colon cancer (0.65, 0.43-0.99) than for proximal colon cancer (0.94, 0.72-1.22, p-common effects = 0.14). Additionally, when comparing different latencies, the overall pattern suggested that the inverse association appeared to be stronger with increasing latency and was strongest for intakes 12-16 years before diagnosis. Comparing total calcium intakes of ≥1,400 vs. <600 mg/d for intake 12-16 y before diagnosis, the pooled RR (95% CIs) of CRC was 0.76 (0.64-0.91). Higher calcium intake was associated with a lower risk of developing colon cancer, especially for distal colon cancer. Overall inverse association was linear and did not differ by intake source. Additionally, calcium intake approximately 10 years before diagnosis appeared to be associated with a lower risk of CRC.

Plasma 25-Hydroxyvitamin D, Vitamin D Binding Protein, and Risk of Colorectal Cancer in the Nurses' Health Study.

Total circulating 25-hydroxyvitamin D [25(OH)D)] has been associated with lower risk of colorectal cancer. The physiologic mechanism, however, may be more directly related to the free or bioavailable fraction of 25(OH)D, which is influenced by levels of vitamin D binding protein (VDBP). We assessed the association of prediagnosis total, free, and bioavailable 25(OH)D and VDBP with colorectal cancer risk among predominantly white women in the Nurses' Health Study (NHS) who provided a blood specimen in 1989-1990. We documented 378 cases of colorectal cancer through 2011 and matched them to 689 controls according to age and time of blood draw. We genotyped two common polymorphisms in the gene coding VDBP and calculated free and bioavailable 25(OH)D levels based on total 25(OH)D, VDBP, albumin, and their estimated genotype-specific binding affinities. Total 25(OH)D was associated with lower colorectal cancer risk (P for trend = 0.01). Compared with women in the lowest quintile of total 25(OH)D, those in the highest quintile had a multivariable-adjusted odds ratio (OR) for colorectal cancer of 0.54 [95% confidence interval (CI), 0.33-0.87]. Comparing extreme quintiles, we did not find any significant association with risk of colorectal cancer for VDBP (OR, 0.98; 95% CI, 0.65-1.47), free 25(OH)D (OR, 0.71; 95% CI, 0.46-1.10), or bioavailable 25(OH)D (OR, 0.92; 95% CI, 0.60-1.42). In conclusion, prediagnosis levels of total, but not free or bioavailable 25(OH)D, were associated with lower colorectal cancer risk. Although our findings support an inverse association of vitamin D with colorectal cancer, this association does not appear to be due to the unbound or bioavailable fraction of circulating vitamin D. Cancer Prev Res; 9(8); 664-72. ©2016 AACR.

Regular Aspirin Use Associates With Lower Risk of Colorectal Cancers With Low Numbers of Tumor-Infiltrating Lymphocytes

Aspirin use reduces colorectal cancerrisk. Aspirin, a nonsteroidal anti-inflammatory drug, inhibits prostaglandin-endoperoxide synthase 2 (PTGS2 or cyclooxygenase-2); PTGS2 promotes inflammation and suppresses T-cell-mediated adaptive immunity. We investigated whether the inverse association of aspirin use with colorectal carcinoma risk was stronger for tumors with lower degrees of lymphocytic infiltrates than for tumors with higher degrees of lymphocytic infiltrates. We collected aspirin use data biennially from participants in the Nurses' Health Study and Health Professionals Follow-up Study. Participants were asked whether they took aspirin in most weeks, the number of tablets taken per week, and years of aspirin use. We collected available tumor specimens (n= 1458) from pathology laboratories in the United States. A pathologist confirmed the diagnosis of colorectal adenocarcinoma (excluding anal squamous cell carcinoma), and evaluated histopathology features, including patterns and degrees of lymphocytic infiltrates within and around tumor areas. Person-years of follow-up evaluation were accrued from the date of return of questionnaires until dates of colorectal cancer diagnosis, death, or the end of follow-up evaluation (June 2010). Duplication-method Cox proportional hazards regression was used to assess the association of aspirin with the incidence of colorectal carcinoma subgroups according to the degree of tumor-infiltrating lymphocytes (TILs), intratumoral periglandular reaction, peritumoral reaction, or Crohn's-like reaction. We documented 1458 rectal and colon cancers. The inverse association between regular aspirin use and colorectal cancer risk significantly differed by concentrations of TILs (Pheterogeneity= .007). Compared with nonregular use, regular aspirin use was associated with a lower risk of tumors that had low levels of TILs (relative risk, 0.72; 95% confidence interval, 0.63-0.81), and strength of the association depended on aspirin dose and duration (both Ptrend < .001). In contrast, aspirin use was not associated with a risk of tumors having intermediate or high levels of TILs. This differential association was consistent regardless of the status of tumor microsatellite instability, mutations in BRAF, or expression of PTGS2. Regular aspirin use was associated with a lower risk of tumors that contained low levels of CD3+ Tcells, CD8+ T cells, or CD45RO (PTPRC)+ T cells (measured by immunohistochemistry and computer-assisted image analysis). Based on data from the prospective cohort studies, regular use of aspirin is associated witha lower risk of colorectal carcinomas with low concentrations of TILs. These findings indicate that the immune response in thetumor microenvironment could be involved in the chemopreventive effects of aspirin.

Abstract 1418: Marine ω-3 polyunsaturated fatty acid intake and risk of colorectal cancer according to tumor-infiltrating T cells

Abstract Importance: Marine ω-3 polyunsaturated fatty acids possess potent immunomodulatory activity and may protect against cancer development. However, evidence relating marine ω-3 polyunsaturated fatty acids to colorectal cancer risk remains inconclusive. Objective: To test the hypothesis that marine ω-3 polyunsaturated fatty acid intake may be associated with lower risk of colorectal cancer subsets characterized by immune infiltrate. Design: Prospective cohort study Setting: Nurses’ Health Study and Health Professionals Follow-up Study Participants: In the two cohorts, 125,172 participants provided data about marine ω-3 polyunsaturated fatty acid intake every 4 years through a validated food frequency questionnaire and followed up for incident colorectal cancer over 24-26 years. We documented 614 colorectal cancer cases from which we could assess T-cell infiltration in the tumor microenvironment. Cause-specific Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals for risks of colorectal cancer subtypes. Exposure: Intake of marine ω-3 polyunsaturated fatty acids Main Outcome and Measures: Incidence of colorectal cancer according to tumor-infiltrating T cells Results: The inverse association of marine ω-3 polyunsaturated fatty acids with colorectal cancer risk differed according to FOXP3+ T-cell infiltration (P for heterogeneity = 0.006). Compared to intake of &amp;lt;0.15 g/day of marine ω-3 PUFAs, intake of ≥0.35 g/day was associated with a multivariable hazard ratio of 0.57 (95% confidence interval, 0.40 to 0.81) (P for trend &amp;lt; 0.001) for FOXP3+ T-cell-high tumors. In contrast, the corresponding hazard ratio was 1.14 (95% confidence interval, 0.81 to 1.60) (P for trend = 0.77) for FOXP3+ T-cell-low tumors. No statistically significant differential association was found according to tumor-infiltrating CD3+, CD8+, or CD45RO+ T cells (P for heterogeneity ≥ 0.34). In functional assays, the suppressive activity of regulatory T cells was approximately two-fold lower when pre-incubated with marine ω-3 polyunsaturated fatty acids at 50, 100 and 200 μM than without marine ω-3 polyunsaturated fatty acids (P&amp;lt;0.0001). Conclusion and Relevance: High marine ω-3 polyunsaturated fatty acid intake was associated with lower risk of colorectal cancer with high-level, but not low-level, FOXP3+ T-cell density, suggesting a potential role of ω-3 polyunsaturated fatty acids in cancer immunoprevention through modulation of regulatory T cells. Citation Format: Mingyang Song, Reiko Nishihara, Yin Cao, Eunyoung Chun, Zhi Rong Qian, Kosuke Mima, Kentaro Inamura, Yohei Masugi, Jonathan Nowak, Katsuhiko Nosho, Kana Wu, Molin Wang, Edward Giovannucci, Wendy S. Garrett, Charles S. Fuchs, Shuji Ogino, Andrew T. Chan. Marine ω-3 polyunsaturated fatty acid intake and risk of colorectal cancer according to tumor-infiltrating T cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1418.

Abstract 1734: Body mass index, physical activity and risk of colorectal cancer in the Korean Multi-center Cancer Cohort (KMCC)

Abstract Objectives: To examine the association between body mass index (BMI), physical activity and colorectal cancer risk among Korean adults. Methods: Data from the Korean Multi-center Cancer Cohort (KMCC) between 1993 and 2005 were analyzed. The study population comprised 12,379 subjects aged above 20 years old. The subjects were followed until December 31, 2011 (median follow-up of 10.1 years). Measured weight and height values was used to calculate BMI and self-reported total time spent for physical activity were used. The Cox proportional hazard model was used to estimate the hazard ratio (HR) and 95% confidence intervals (CI) of BMI and physical activity for colorectal cancer risk. Results: Men who did moderate physical activity showed a lower risk for colorectal cancer (HR 0.35, 95% CI: 0.19-0.65 for 30-419 minutes compared to who spend less than 30 minutes a week doing moderate activities). We did not find any association between the total time of vigorous activities and muscle-strengthening activities and colorectal cancer risk in both men and women. Men with BMI of 25 or higher showed an increased risk for colorectal cancer compared to men with BMI of 18.5 to 22.9 (HR 1.64, 95% CI 0.94-2.88 for 25.0-29.9 kg/m2; HR 1.64, 95% CI 0.94-2.88 for greater than 30.0 kg/m2). Conclusions: Moderate physical activities were associated with lower colorectal cancer risk among Korean men. Citation Format: Sooyoung Cho, Aesun Shin, Sue K. Park, Hai-Rim Shin, Soung-Hoon Chang, Keun-Young Yoo. Body mass index, physical activity and risk of colorectal cancer in the Korean Multi-center Cancer Cohort (KMCC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1734.

Diet Quality and Colorectal Cancer Risk in the Women's Health Initiative Observational Study.

Diet quality index scores on Healthy Eating Index 2010 (HEI-2010), Alternative HEI-2010, alternative Mediterranean Diet Index, and the Dietary Approaches to Stop Hypertension (DASH) index have been inversely associated with all-cause and cancer-specific death. This study assessed the association between these scores and colorectal cancer (CRC) incidence as well as CRC-specific mortality in the Women's Health Initiative Observational Study (1993-2012), a US study of postmenopausal women. During an average of 12.4 years of follow-up, there were 938 cases of CRC and 238 CRC-specific deaths. We estimated multivariate hazard ratios and 95% confidence intervals for relationships between quintiles of diet scores (from baseline food frequency questionnaires) and outcomes. HEI-2010 score (hazard ratios were 0.81, 0.77, and 0.73 with P values of 0.04, 0.01, and <0.01 for quintiles 3-5 vs. quintile 1, respectively) and DASH score (hazard ratios were 0.72, 0.74, and 0.78 with P values of <0.01, <0.01, and 0.03 for quintiles 3-5 vs. quintile 1, respectively), but not other diet scores, were associated with a lower risk of CRC in adjusted models. No diet scores were significantly associated with CRC-specific mortality. Closer adherence to HEI-2010 and DASH dietary recommendations was inversely associated with risk of CRC in this large cohort of postmenopausal women.

Parkinson’s disease and colorectal cancer risk—A nested case control study

BackgroundA pro-inflammatory gut microbiota was described in both Parkinson’s disease and colorectal cancer (CRC) and recently α-synuclein was demonstrated in the enteric nervous system. We sought to evaluate the association between Parkinson’s disease and CRC. MethodsWe conducted a nested case-control study using a large primary-care database. Cases were defined as all individuals with CRC. Up to 4 controls were matched with each case based on age, sex, practice-site and duration of follow-up. The primary exposure of interest was diagnosis of Parkinson’s disease prior to CRC as well as disease duration, and Parkinson’s specific therapies. The primary analysis was a conditional logistic-regression to estimate odds ratios (ORs) and 95% confidence interval (95%CI). ResultsThe study included 22,093 CRC cases and 85,833 matched controls. Past medical history of Parkinson’s disease >1 year before index-date was associated with lower CRC risk (OR 0.74, 95%CI 0.59–0.94). The inverse association was more prominent among females compared to males (0.64, 95%CI 0.42–0.96 and 0.8, 95%CI 0.60–1.07, respectively). While patients who received no therapy or therapy with dopamine agonists had a non-significant decrease in cancer risk, patients who were treated with dopamine had a non-significant elevated cancer risk. ConclusionParkinson’s disease is inversely associated with CRC risk.

Inverse associations of dietary fiber and menopausal hormone therapy with colorectal cancer risk in the Multiethnic Cohort Study.

In the Multiethnic Cohort Study, we previously reported that dietary fiber intake was inversely associated with colorectal cancer risk in men only. In women, the inverse relationship was weaker and appeared to be confounded by menopausal hormone therapy (MHT). We re-examined this observation with a greatly increased power. Using Cox proportional hazards models, we analyzed data from 187,674 participants with 4,692 cases identified during a mean follow-up period of 16 years. In multivariable-adjusted models, dietary fiber intake was inversely associated with colorectal cancer risk in both sexes: HR = 0.73, 95% CI: 0.61-0.89 for highest vs. lowest quintile, ptrend = 0.0020 in men and HR = 0.76, 95% CI: 0.62-0.91, ptrend = 0.0067 in women. Postmenopausal women who ever used MHT had a 19% lower risk of colorectal cancer (95% CI: 0.74-0.89) compared with MHT never users. In a joint analysis of dietary fiber and MHT, dietary fiber intake was associated with a lower colorectal cancer risk in MHT never users (HR = 0.75, 95% CI: 0.59-0.95, ptrend = 0.045), but did not appear to further decrease the colorectal cancer risk of MHT ever users (ptrend = 0.11). Our results support the overall protective roles of dietary fiber and MHT against colorectal cancer and suggest that dietary fiber may not lower risk further among women who ever used MHT. If confirmed, these results would suggest that MHT and dietary fiber may share overlapping mechanisms in protecting against colorectal cancer.

A prospective study of soluble receptor for advanced glycation end-products and colorectal cancer risk in postmenopausal women

ObjectivesReceptor for advanced glycation end products (RAGE) expressed on adipocytes and immune cells can bind to ligand Nε-(carboxymethyl)-lysine (CML) and trigger dysregulation of adipokines and chronic inflammation. Soluble RAGE (sRAGE) mitigates the detrimental effect of RAGE. We examined the associations between circulating levels of CML-AGE and sRAGE and colorectal cancer (CRC). MethodsIn a case-cohort study of the Women⿿s Health Initiative Study, blood levels of CML-AGE and sRAGE were measured using ELISA. We used multivariable Cox regression model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of incident CRC in relation to quartiles (Q) of biomarker levels. ResultsAverage follow-up was 7.8 years for 444 cases and 805 subcohort members. In the subcohort, CML-AGE and sRAGE were inversely correlated with BMI (P values<0.0001). Levels of CML-AGE and sRAGE were not associated with CRC. In BMI-specific analysis, the association between sRAGE and CRC was observed. Among women with BMI⿥25kg/m2, those with highest levels of sRAGE had significantly lower risk for CRC as compared to women with lowest levels of sRAGE (HRQ4versusQ1: 0.39; 95% CI: 0.17⿿0.91). This inverse association was not observed among women with BMI <25kg/m2 (P value for interaction=0.01). ConclusionsAmong postmenopausal women, the RAGE pathway may be involved in obesity-related CRC.

The PI3K/Akt pathway is involved in procyanidin-mediated suppression of human colorectal cancer cell growth.

Colorectal cancer (CRC) has the third highest incidence worldwide. Epidemiological studies showed that the consumption of fruit and vegetables containing procyanidins (PCA), polymers of flavan-3-ols, is associated with lower CRC risk. However, the molecular mechanisms supporting this positive association are unclear. This study investigated the capacity of PCA with different degrees of polymerization to reduce CRC cell growth, characterizing the underlying mechanisms. Compared to the monomer ((-)-epicatechin) and the trimer, the hexamer (Hex) was the most active at reducing CRC cell viability. Hex caused a concentration- (2.5-50 μM) and time- (24-72 h) dependent decrease in the viability of six human CRC cell lines in culture. Hex caused CRC apoptotic Caco-2 cell death within 24 h, as evidenced by caspase 3 and caspase 9 activation, DNA fragmentation, and changes in nuclear morphology/staining. Hex-induced apoptosis occurs through the mitochondrial pathway, as evidenced by an increased Bad mitochondrial translocation, and cytochrome c release from the mitochondria to the cytosol. Hex also arrested the Caco-2 cell cycle at G2 /M phase and upregulated genes involved in autophagy. Mechanistically, in Caco-2 cells Hex inhibited the PI3K/Akt signaling pathway, causing the downstream downregulation of proteins involved in the regulation of cell survival (Bad, GSK-3β). Accordingly, the Akt inhibitor MKK-2206 decreased Bad and GSK-3β phosphorylation. MKK-2206 decreased cell growth, having an additive effect with Hex. In conclusion, our results show that large PCA can inhibit CRC cell growth via the Akt kinase pathway, demonstrating a mechanism to explain the epidemiological evidence linking PCA-rich diets with lower CRC risk. © 2016 Wiley Periodicals, Inc.

The Impact of Life Style and Nutritional Components in Primary Prevention of Colorectal Cancer

Antiproliferative and apoptotic activity of crude skin secretion from Malaysian Toad (Bufo asper) on in vitro colorectal cancer cellsSaad Sabbar Dahham, Muhammad Asif, Yasser M Tabanaa , Doblin Sandai, Amin Malik Shah Abdul Majid, Gam Lay Harn

Clinical risk factors of colorectal cancer in patients with serrated polyposis syndrome: a multicentre cohort analysis

ObjectiveSerrated polyposis syndrome (SPS) is accompanied by an increased risk of colorectal cancer (CRC). Patients fulfilling the clinical criteria, as defined by the WHO, have a wide variation in CRC...