Reduced Risk Of Colorectal Cancer Research Articles

Greenness Exposure in Relation to Residing in Areas of High Colorectal Cancer in Kentucky

BACKGROUND AND AIM: Colorectal cancer (CRC) is the third most common in the US. Natural vegetation exposure, also called greenness, is associated with CRC risk-reducing behaviors like lower BMI and increased physical activity. Studies concerning greenness and CRC are sparse. The aims were to identify high-incidence clusters for CRC in Kentucky and examine the relationship between residential greenness and residing in areas of high CRC incidence. We hypothesize that lower greenness is associated with living in areas of higher CRC incidence. METHODS: We calculated age-standardized CRC rates from the 1995-2018 Kentucky Cancer Registry. Spatial cluster analyses identified CRC hotspot census tracts. The Normalized Difference Vegetation Index (NDVI) is a commonly used measure of greenness. Residential addresses of CRC cases diagnosed between 1996-2015 (n=49,540) were linked to 5-year average NDVI before diagnosis and to census tract estimates of socioeconomic factors and rural-urban designations. Logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for a standard deviation increase in NDVI in relation to residing in a CRC hotspot, adjusting for demographic, socioeconomic, and lifestyle factors. We assessed effect modification by urbanicity. RESULTS:Residential greenness was inversely associated with odds of residing in a CRC hotspot (OR=0.48, 95%CI 0.45, 0.50), adjusting for demographics, marital status, insurance, family history, smoking, physical inactivity, obesity, and neighborhood economic factors. The association was modified by urbanicity with urban cases (adjusted OR 0.52 95%CI 0.49, 0.56) having lower odds of residing in a hotspot with one standard deviation increase in NDVI than rural cases (adjusted OR=0.68 95%CI 0.57-0.80) adjusting for aforementioned factors. CONCLUSIONS:Residential greenness was inversely associated with residing in a CRC hotspot. Individuals in urban areas may experience a greater reduction in CRC risk from greenness exposure than individuals in rural areas. More robust epidemiologic studies should evaluate greenness and colorectal cancer incidence. KEYWORDS: green space, cancer and cancer precursors, environmental epidemiology

Diet quality indices and gastrointestinal cancer risk: results from the Lifelines study

ObjectiveTo investigate the long-term association between four dietary quality indices and the risk of gastrointestinal (GI) cancer.MethodsBaseline details of the dietary intake of participants, assessed by a single food frequency questionnaire from the prospective Lifelines population-based cohort were translated to diet quality scores using several dietary and dietary-lifestyle indices. Incident cases of GI cancer were then assessed by linkage to the Dutch nationwide histo-cytopathology registry. The association between GI cancer risk and diet quality (defined as higher quintiles on dietary indices compared to the first quintile) was assessed by multivariable Cox proportional hazard models.ResultsWe included 72,695 participants aged 51.20 ± 8.71 years with a median follow-up to cancer diagnosis of 8 years (interquartile range 2 years). During follow-up, 434 colorectal cancers and 139 upper GI cancers were diagnosed. There was a significant reduction in colorectal cancer risk for high categories in the American Cancer Society (ACS) Index (hazard ratio 0.62; 95% CI 0.46–0.84). However, high dietary index scores were not associated with strong beneficial effects on upper GI cancer risk.ConclusionHigh quintiles on the ACS Index were associated with a significantly reduced risk of colorectal cancer. This index may be of use in a colorectal cancer prevention program.

An RCT of a decision aid to support informed choices about taking aspirin to prevent colorectal cancer and other chronic diseases: a study protocol for the SITA (Should I Take Aspirin?) trial

BackgroundAustralian guidelines recommend that all people aged 50–70 years old actively consider taking daily low-dose aspirin (100–300 mg per day) for 2.5 to 5 years to reduce their risk of colorectal cancer (CRC). Despite the change of national CRC prevention guidelines, there has been no active implementation of the guidelines into clinical practice.We aim to test the efficacy of a health consultation and decision aid, using a novel expected frequency tree (EFT) to present the benefits and harms of low dose aspirin prior to a general practice consultation with patients aged 50–70 years, on informed decision-making and uptake of aspirin.MethodsApproximately five to seven general practices in Victoria, Australia, will be recruited to participate. Patients 50–70 years old, attending an appointment with their general practitioner (GP) for any reason, will be invited to participate in the trial. Two hundred fifty-eight eligible participants will be randomly allocated 1:1 to intervention or active control arms using a computer-generated allocation sequence stratified by general practice, sex, and mode of trial delivery (face-to-face or teletrial).There are two co-primary outcomes: informed decision-making at 1-month post randomisation, measured by the Multi-dimensional Measure of Informed Choice (MMIC), and self-reported daily use of aspirin at 6 months. Secondary outcomes include decisional conflict at 1-month and other behavioural changes to reduce CRC risk at both time points.DiscussionThis trial will test the efficacy of novel methods for implementing national guidelines to support informed decision-making about taking aspirin in 50–70-year-olds to reduce the risk of CRC and other chronic diseases.Trial registrationThe Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12620001003965. Registered on 10 October 2020.

Abstract 815: Genome-wide gene-calcium interaction in relation to colorectal cancer risk

Abstract Calcium intake has been associated with a decreased risk of colorectal cancer (CRC). However, the role of germline genetics and the molecular mechanisms underlying this association have not been fully elucidated. In previous gene-environment studies, several single nucleotide polymorphisms (SNPs), including some associated with genes involved in calcium reabsorption, have been identified but with limited statistical power. In this study, we aimed to investigate SNP interactions with calcium intake in relation to CRC risk in the largest study to date. We performed a genome-wide interaction study (GWIS) using genotype and self-reported calcium intake information from 31,007 CRC cases and 41,683 controls (n=72,690) of European ancestry from 46 studies within the GECCO study. We ran the analysis with the GxEScanR package and adjusted the models by sex, age, study, total energy intake, and genetic ancestry (3 principal components). Higher total calcium (dietary and supplemental) intake was associated with reduced CRC risk (OR per quartile, 0.83; 95% CI, 0.78-0.89). Similar results were found for dietary calcium intake and for stratified analyses by sex and anatomic location (proximal, distal and rectum). Total calcium intake was strongly associated with SNPs near the MCM6 gene, related to lactose intolerance. In the GWIS results, we found 60 and 82 SNPs (suggestive hits, P values < 5e-6) interacting with total and dietary calcium intake, respectively, in relation to CRC risk, some located in genes such as CNTNAP2, SHFM1, PEBP4, NRDE2, PLA2G4D, SLC26A11, ZNF45, and PLA2G4D. No variants reached the 10-8 threshold. Finally, we performed annotation in open chromatin regions, expression quantitative trait loci (eQTLs) and genes differentially expressed according to calcium intake in colon tissue. In conclusion, our preliminary results provide suggestive loci for gene-calcium interaction in relation to CRC risk, which may give insights into the molecular mechanisms underlying the preventive role of calcium in this type of cancer. Further analyses will include joint association tests, two-step methods and additive and multiplicative polygenic risk score analyses. Citation Format: Virginia Díez-Obrero, Fränzel van Duijnhoven, Andre E. Kim, James Baurley, Peter T. Campbell, Robert Carreras-Torres, Jenny Chang-Claude, David V. Conti, Mazda Jenab, Li Hsu, Kristina M. Jordahl, Juan Pablo Lewinger, Yi Lin, Polly A. Newcomb, Mireia Obón-Santacana, Pardamean Bens, Peoples Anita, Conghui Qu, Edward Ruiz-Narvaez, Yu Tian, Kostas Tsilidis, Graham Casey, Ulrike Peters, James W. Gauderman, Victor Moreno. Genome-wide gene-calcium interaction in relation to colorectal cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 815.

Abstract 818: Association of polygenic risk score and menopausal hormone therapy for colorectal cancer risk

Abstract Background and objective Genetic predisposition and menopausal hormone therapy (MHT) are established risk and preventive factors for colorectal cancer (CRC), respectively. We aimed to evaluate the joint associations of a polygenic risk score (PRS) and MHT on CRC risk for informing CRC prevention. Methods We used data from 28,486 postmenopausal women (11,519 cases and 16,967 controls) of European descent from 38 studies. MHT use was assessed as the use of any MHT, estrogen-only (E-only) or combined estrogen-progestogen (E+P) therapy at reference time. A PRS based on 141 genetic variants previously identified by genome-wide association studies of CRC was modelled as categorical variable in quartiles and also as per-standard deviation difference between PRS and minimum of PRS [(PRS-min(PRS))/SD(PRS)] (PRS.minsd). Multiplicative interaction between PRS and MHT was evaluated using standard logistic regression. Additive interaction was measured using the relative excess risk due to interaction (RERI). Results The use of any MHT as well as E+P and E-only were associated with reduced CRC risk (Odds ratio [OR] 0.70, 0.71, 0.65, respectively). PRS was associated with increased CRC risk, whether as continuous variable (PRS.minsd) (OR 1.53) or in quartiles (OR 1.49, 1.92, 2.87, respectively). We identified statistically significant negative multiplicative interaction (OR: 0.92; 95%CI: 0.87, 0.98) as well as negative additive interaction (RERI: -0.13; 95%CI: -0.15, -0.10) between PRS.minsd and any MHT use. Results were limited to additive interactions with PRS.minsd for E-only use (RERI: -0.14; 95%CI: -0.18, -0.11) and E+P use (RERI: -0.12; 95%CI: -0.16, -0.08). The magnitude of negative additive interactions increased with higher quartiles of PRS for all MHT variables and was consistently significant for the highest quartile compared to the lowest quartile of PRS for any MHT use (RERI: -0.78; 95%CI: -1.03, -0.52), E-only use (RERI: -0.78; 95%CI: -1.18, -0.39), and also E+P use (RERI: -0.53; 95%CI: -0.96, -0.10). Negative multiplicative interaction was also observed for higher PRS quartiles of all MHT variables but significant only for the highest quartile with E-only use (OR: 0.73; 95%CI: 0.55, 0.97). These negative interactions on both multiplicative and additive scales indicate that MHT has a relatively more protective effect on CRC risk for those women with larger PRS scores. For example, compared to women in the lowest PRS quartile with no MHT use, the risk of CRC for women in higher quartiles of PRS was more strongly reduced with MHT use (ORPRS.Q3+noMHT: 1.93 vs ORPRS.Q3+MHT: 1.38, OR MHT/noMHT in PRS.Q3: 0.71; ORPRS.Q4+noMHT: 2.81 vs ORPRS.Q4+MHT: 1.77, OR MHT/noMHT in PRS.Q4: 0.63). Conclusions The protective effect of MHT use on the risk of CRC is stronger in women with higher genetic risk. Risk prediction models incorporating PRS may need to account for potential effect modification by non-genetic risk factors. Citation Format: Yu Tian, Yi Lin, Andre E. Kim, Stephanie A. Bien, Polly A. Newcomb, Graham Casey, Elizabeth A. Platz, Loic Le Marchand, Peter T. Campbell, Hermann Brenner, Michael Hoffmeister, Feng Guo, Xuechen Chen, Marc J. Gunter, Niki Dimou, Stephen B. Gruber, Andrew T. Chan, Amit D. Joshi, Sonja I. Berndt, Emily White, Victor Moreno, Ross L. Prentice, Ulrike Peters, William Gauderman, Li Hsu, Jenny Chang-Claude. Association of polygenic risk score and menopausal hormone therapy for colorectal cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 818.

Abstract 825: Genetically determined elevated C-reactive protein levels and chronic inflammation status associated with primary colorectal cancer risk: Mendelian randomization with lifestyle interactions

Abstract Purpose: Immune-related etiologic pathways in the development of colorectal cancer (CRC) have not been convincingly determined and may be confounded by lifestyle factors or reverse causality. We investigated the genetically predicted C-reactive protein (CRP) phenotype in the potential causal pathway of primary CRC risk in postmenopausal women in a Mendelian randomization (MR) framework. Methods: We employed individual-level data of the Women's Health Initiative Database for Genotypes and Phenotypes Study, which consists of 5 genome-wide association (GWA) studies, including 10,142 women, 737 of whom developed primary CRC. We examined 61 GWA single-nucleotide polymorphisms (SNPs) associated with CRP by using weighted/penalized MR weighted-medians and MR gene-environment interactions that allow some relaxation of the strict variable requirements and attenuate the heterogeneous estimates of outlying SNPs. Results: In lifestyle-stratification analyses, genetically determined CRP exhibited its effects on the decreased CRC risk in non-viscerally obese and high-fat diet subgroups. In contrast, genetically driven CRP was associated with an increased risk for CRC in women who smoked 15 or more cigarettes/day, with significant interaction of the gene-smoking relationship. Further, a substantially increased risk of CRC induced by CRP was observed in relatively short-term users (less than 5 years) of estrogen (E)-only and also longer-term users (longer than 5 years) of E plus progestin. Conclusions: Our findings may provide novel evidence on immune-related etiologic pathways connected to CRC risk and suggest the possible use of CRP as a CRC-predictive biomarker in women with particular behaviors and CRP marker-informed interventions to reduce CRC risk. Citation Format: Su Yon Jung, Herbert Yu, Matteo Pellegrini, Jeanette C. Papp, Eric M. Sobel, Zuo-Feng Zhang. Genetically determined elevated C-reactive protein levels and chronic inflammation status associated with primary colorectal cancer risk: Mendelian randomization with lifestyle interactions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 825.

Phytochemically rich dietary components and the risk of colorectal cancer: A systematic review and meta-analysis of observational studies.

BACKGROUNDPersonalized nutrition and protective diets and lifestyles represent a key cancer research priority. The association between consumption of specific dietary components and colorectal cancer (CRC) incidence has been evaluated by a number of population-based studies, which have identified certain food items as having protective potential, though the findings have been inconsistent. Herein we present a systematic review and meta-analysis on the potential protective role of five common phytochemically rich dietary components (nuts, cruciferous vegetables, citrus fruits, garlic and tomatoes) in reducing CRC risk.AIMTo investigate the independent impact of increased intake of specific dietary constituents on CRC risk in the general population.METHODSMedline and Embase were systematically searched, from time of database inception to January 31, 2020, for observational studies reporting CRC incidence relative to intake of one or more of nuts, cruciferous vegetables, citrus fruits, garlic and/or tomatoes in the general population. Data were extracted by two independent reviewers and analyzed in accordance with the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) reporting guidelines and according to predefined inclusion/exclusion criteria. Effect sizes of studies were pooled using a random-effects model.RESULTSForty-six studies were identified. CRC risk was significantly reduced in patients with higher vs lower consumption of cruciferous vegetables [odds ratio (OR) = 0.90; 95% confidence interval (CI): 0.85-0.95; P < 0.005], citrus fruits (OR = 0.90; 95%CI: 0.84-0.96; P < 0.005), garlic (OR = 0.83; 95%CI: 0.76-0.91; P < 0.005) and tomatoes (OR = 0.89; 95%CI: 0.84-0.95; P < 0.005). Subgroup analysis showed that this association sustained when looking at case-control studies alone, for all of these four food items, but no significant difference was found in analysis of cohort studies alone. Nut consumption exhibited a similar trend, but overall results were not significant (OR = 0.72; 95%CI: 0.50-1.03; P < 0.07; I2 = 90.70%). Putative anticarcinogenic mechanisms are proposed using gene-set enrichment analysis of gene/protein perturbations caused by active compounds within each food item.CONCLUSIONIncreased cruciferous vegetable, garlic, citrus fruit and tomato consumption are all inversely associated with CRC risk. These findings highlight the potential for developing precision nutrition strategies for CRC prevention.

Non-steroidal anti-inflammatory drugs, polygenic risk score and colorectal cancer risk.

The regular use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with reduced colorectal cancer (CRC) risk. To explore whether this association varies according to background polygenic risk for CRC. Data were collected from a large population-based case-control study on CRC in Germany. A polygenic risk score (PRS) based on 140 CRC-related risk loci was used to quantify the genetic risk. The associations of regular use of NSAIDs (≥2times per week for at least 1year) with CRC risk were estimated in the whole population and in subgroups according to PRS levels using multivariable logistic regression. The impact of NSAIDs on CRC risk was compared to PRS using the 'genetic risk equivalent' (GRE), a recently developed metric for effective risk communication. In total 5129 CRC cases and 4093 controls were included in this analysis. The regular use of NSAIDs (including aspirin) was associated with reduced CRC risk [odds ratio (OR) 0.66, 95% confidence interval (CI) 0.59, 0.74], as was regular use of aspirin only (OR 0.73, 95% CI 0.65, 0.83), without indication of interaction with the PRS (P=0.10 and 0.22 respectively). The effect of NSAID use was equivalent to the effect of having a 32 percentiles lower PRS (GRE -32, 95% CI -41, -22). The regular use of NSAIDs is associated with greatly reduced CRC risk regardless of individual genetic profile. With an equivalent reduction of relative risk across all polygenic risk groups, absolute risk reduction would be expected to be strongest among those with the highest polygenic risk score.

Early-Age Onset Colorectal Neoplasia in Average-Risk Individuals Undergoing Screening Colonoscopy: A Systematic Review and Meta-Analysis

Incidence and mortality associated with early-age onset colorectal cancer (EAO-CRC) is increasing, prompting professional society recommendations to lower the screening age in average-risk individuals. The yield of screening individuals younger than 50 years is not known. A systematic review of 3 databases from inception through July 2020 was performed in all languages that reported colonoscopy findings in average-risk individuals younger than 50 years. The primary outcomes were EAO colorectal neoplasia (CRN) and advanced colorectal neoplasia (aCRN) prevalence. Subgroup analyses were performed based on sex, geographic location, time period, and age, including comparison with those aged 50-59 years. Generalized linear mixed model with random intercept logistic regression and fixed subgroup effects were performed. Of 10,123 unique articles, 17 studies published between 2002 and 2020, including 51,811 average-risk individuals from 4 continents, were included. The pooled rate of EAO-CRN was 13.7% (95% confidence interval [CI], 0.112%-0.168%) and EAO-aCRN was 2.2% (95% CI, 0.016%-0.031%). Prevalence of CRC was 0.05% (95% CI, 0.00029%-0.0008%). Rates of EAO-CRN were higher in men compared with women (relative risk, 1.71%; 95% CI, 1.49%-1.98%), and highest in the United States (15.6%; 95% CI, 12.2%-19.7%) compared with Europe (14.9%; 95% CI, 6.9%-29.3%), East Asia (13.4%; 95% CI, 10.3%-17.2%), and the Middle East (9.8%; 95% CI, 7.8%-12.2%) (P= .04) The rate of EAO-CRN in age groups 45-49 years and 50-59 years was 17.8% (95% CI, 14.5%-21.6%) and 24.8% (95% CI, 19.5%-30.8%), respectively (P= .04). The rate of EAO-aCRN in age group 45-49 years was 3.6% (95% CI, 1.9%-6.7%) and 4.2% (95% CI, 3.2%-5.7%), respectively (P= .69). The rate of aCRN in individuals aged 45-49 years was similar to the rate observed in individual aged 50-59 years, suggesting that expanding screening to this population could yield a similar impact on colorectal cancer risk reduction.

Dietary vitamin D intake and colorectal cancer risk: a longitudinal approach within the PREDIMED study.

We evaluated whether the intake of dietary vitamin D is associated with the incidence of both colorectal cancer (CRC) and colon cancer in the framework of the PREDIMED cohort of older adults at high cardiovascular risk. We analyzed data from 7216 men and women (55-80years) without CRC at baseline from the PREvención con DIeta MEDiterránea study. Baseline consumption of vitamin D was assessed using a validated 137-item food frequency questionnaire. Cox proportional hazards ratios (HRs) of CRC and colon cancer incidence were estimated for quartiles and per 1-SD of baseline vitamin D intake. During a median follow-up of 6years, we documented 97 incident CRC cases after the exclusion of subjects with no baseline dietary data and/or outliers of energy intake. A non-significant HRs and 95% confidence intervals (CIs) of CRC for the comparison of extreme quartiles (4th vs 1st) of vitamin D intake were observed [0.55 (0.30-1.00), P for trend = 0.072], whereas it was significant for colon cancer incidence alone [0.44 (0.22-0.90), P for trend = 0.032]. However, this association became significant in CRC and colon cancer incidence, after excluding 391 subjects consuming baseline vitamin D and/or calcium medication or prescribed supplements [0.52 (0.28-0.96) and 0.41 (0.12-0.85), respectively]. A higher dietary intake of vitamin D was significantly associated with a reduced CRC risk in individuals at high cardiovascular risk.

P155 Bowel preparation is valued more than colorectal cancer risk and interval by patients in colitis-associated colorectal cancer surveillance: a discrete choice experiment

Abstract Background Patients with inflammatory bowel disease (IBD) undergo surveillance colonoscopies at fixed intervals to reduce the risk of colorectal cancer (CRC). Taking patients’ preferences for determining surveillance strategies into account could improve adherence and patient satisfaction. This study aimed to determine patient preferences and preference heterogeneity for CRC surveillance in IBD. Methods We conducted a web-based, multicentre, discrete choice experiment among adult IBD patients with an indication for surveillance, treated in two academic and one general teaching hospital in The Netherlands. Individuals were repeatedly asked to choose between three hypothetical surveillance scenarios and indicate if they would prefer this option in real-life. The choice tasks were based on bowel preparation (0.3-4L), CRC risk reduction (8% to 1–6%), and interval (1–10 years). Attribute importance scores, trade-offs, and willingness to participate were calculated using a multinomial logit model. Latent class analysis was used to identify subgroups with similar preferences. Results In total, 301 of 386 questionnaires sent out were completed and included in the study. The attributes and levels in the choice tasks significantly affected patients’ preferences. Bowel preparation was the most valued attribute (importance score 40.0%), followed by surveillance interval and CRC risk reduction (respectively 30.9% and 29.0%). Maximal CRC risk reduction, low-volume bowel preparation (0.3L laxative with 2L clear liquid) with two-yearly surveillance was the most preferred combination. Patients were willing to exchange a surveillance interval from three-yearly to annually for a CRC risk reduction of 2.9%. In latent class analysis, three subgroups were identified (figure 1). Willingness to participate in CRC surveillance was high, with only five patients (1.7%) always choosing ‘no surveillance’. Perceived high burden of bowel preparation and lower age were significantly associated with the ‘laxative avoidant’ group compared to the reference group ‘surveillance preferent’ (univariable odds ratio (OR) 2.92, 95% CI (confidence interval) 1.63–5.23 and OR 0.96, 95% CI 0.94–0.98, respectively). High level of education and age significantly differed in the ‘CRC risk avoidant’ group (univariable OR 3.77, 95% CI 2.11–6.75 and 0.94, 95% CI 0.92–0.96). Figure 1: Attribute importance scores Higher scores indicate more relative importance [0=not important at all; 100=most important] Conclusion Bowel preparation is seen as the most important factor by patients in CRC surveillance in IBD. Heterogeneity in preferences can be explained by three latent subgroups. Surveillance adherence could benefit from these findings.

Histology, Size, and Number of Advanced Polyps are Associated With Guideline-Discordant Surveillance Recommendations

Surveillance guidelines following polypectomy promote cost-effective reductions in future colorectal cancer (CRC) risk, but high nonadherence rates1 can have negative consequences on costs and effectiveness. Professional societies recommend a 3-year interval for patients with advanced colorectal polyps (ACPs), although few studies report provider adherence to surveillance intervals.2 This study evaluated rates and predictors of guideline-discordant recommendations for patients with ACPs.

Regulation and Consumer Interest in an Antioxidant-Enriched Ham Associated with Reduced Colorectal Cancer Risks.

An economic experiment was conducted in France in 2020 to evaluate consumer attitudes toward two ham products associated with different colorectal cancer risks. We focused specifically on comparing a conventional ham and a new hypothetical antioxidant-enriched ham with a reduced risk of provoking colorectal cancer. Study participants were given descriptions of the two hams before carrying out successive rounds of willingness-to-pay (WTP) assessments. The results show that WTP was higher for the antioxidant-enriched ham than for the conventional ham. WTP estimates were also impacted by providing additional information about the reduction in colorectal cancer risk associated with the antioxidant-enriched ham. Based on the participants’ WTP, we came up with ex ante estimates for the social impacts of introducing the antioxidant-enriched ham onto the market, and we suggest that it would be socially optimal to promote the product. Competition arising from pre-existing product labelling and marketing assertions could greatly limit the market potential of antioxidant-enriched ham, which suggests that alternative approaches may be necessary, such as regulations mandating antioxidant enrichment. These results also concern all countries with high levels of meat consumption.

Effects of Screenings in Reducing Colorectal Cancer Incidence and Mortality Differ by Polygenic Risk Scores.

INTRODUCTION:Colorectal cancer (CRC) screening reduces CRC incidence and mortality. However, it is unclear whether the reduction in CRC risk may differ by genetic susceptibility.METHODS:We evaluated this question in a cohort of 304,740 participants of European descent aged 50 years and older. Genetic susceptibility was measured using a polygenic risk score (PRS) constructed with risk variants identified in genomewide association studies. Cox models were used to estimate hazard ratios and 95% confidence intervals of CRC risk.RESULTS:Over a median follow-up of 7.0 years, 2,261 incident CRC cases and 528 CRC deaths were identified. CRC screening was associated with a significantly reduced CRC incidence among individuals with a high (hazard ratio, 0.80; 95% confidence interval, 0.71–0.92) and intermediate PRS (0.84, 0.71–0.98) but not among those with a low PRS (1.03, 0.86–1.25; Pinteraction, 0.005). A similar but more evident difference was observed for mortality (Pinteraction, 0.046), with more than 30% reduced mortality observed in the high PRS group (0.69, 0.52–0.91). Among the younger group (age 50–60 years), CRC screenings were associated with a slightly (but nonsignificantly) elevated incidence and mortality in the low PRS group but a reduced risk in the high PRS group (Pinteraction, 0.043 [incidence]; 0.092 [mortality]). No significant interaction was observed in the older group (age > 60 years).DISCUSSION:Individuals with a higher genetic risk benefited more substantially from CRC screenings than those with a lower risk. Our findings suggest that PRS may be used to develop personalized CRC screening to maximize its effect on CRC prevention.

Can Cost-effectiveness Analysis Inform Genotype-Guided Aspirin Use for Primary Colorectal Cancer Prevention?

Inherited genetic variants can modify the cancer-chemopreventive effect of aspirin. We evaluated the clinical and economic value of genotype-guided aspirin use for colorectal cancer chemoprevention in average-risk individuals. A decision analytical model compared genotype-guided aspirin use versus no genetic testing, no aspirin. The model simulated 100,000 adults ≥50 years of age with average colorectal cancer and cardiovascular disease risk. Low-dose aspirin daily starting at age 50 years was recommended only for those with a genetic test result indicating a greater reduction in colorectal cancer risk with aspirin use. The primary outcomes were quality-adjusted life-years (QALY), costs, and incremental cost-effectiveness ratio (ICER). The mean cost of using genotype-guided aspirin was $187,109 with 19.922 mean QALYs compared with $186,464 with 19.912 QALYs for no genetic testing, no aspirin. Genotype-guided aspirin yielded an ICER of $66,243 per QALY gained, and was cost-effective in 58% of simulations at the $100,000 willingness-to-pay threshold. Genotype-guided aspirin was associated with 1,461 fewer polyps developed, 510 fewer colorectal cancer cases, and 181 fewer colorectal cancer-related deaths. This strategy prevented 1,078 myocardial infarctions with 1,430 gastrointestinal bleeding events, and 323 intracranial hemorrhage cases compared with no genetic testing, no aspirin. Genotype-guided aspirin use for colorectal cancer chemoprevention may offer a cost-effective approach for the future management of average-risk individuals. A genotype-guided aspirin strategy may prevent colorectal cancer, colorectal cancer-related deaths, and myocardial infarctions, while minimizing bleeding adverse events. This model establishes a framework for genetically-guided aspirin use for targeted chemoprevention of colorectal cancer with application toward commercial testing in this population.

Healthy lifestyles, genetic modifiers, and colorectal cancer risk: a prospective cohort study in the UK Biobank

Both genetic and lifestyle factors play an etiologic role in colorectal cancer (CRC). We evaluated potential gene-environment interactions in CRC risk. We used data from 346,297 participants in the UK Biobank cohort. Healthy lifestyle scores (HLSs) were constructed using 8 lifestyle factors, primarily according to the American Cancer Society guidelines, and were categorized into unhealthy, intermediate, and healthy groups. A polygenic risk score (PRS) was created using 95 genetic risk variants identified by genome-wide association studies of CRC and was categorized by tertile. Cox models were used to estimate the HRs and 95% CIs of CRC risk associated with the HLS and PRS. During a median follow-up of 5.8 y, 2066 incident cases of CRC were identified. Healthier HLSs were associated with reduced risk of CRC in a dose-response manner. The risk reduction was more apparent among those with high PRS (HRhealthy vs. unhealthy HLS1: 0.58; 95% CI: 0.43, 0.79 for men and 0.71; 0.58, 0.85 for men and women combined) than those with low PRS. Although no multiplicative interactions were identified, the HLS1 and PRS showed a significant additive interaction (P=0.02 for all participants combined, 0.04 for men). In analyses including all participants, the adjusted CRC cumulative risk from age 40 to 75 y was 6.40% for those with high PRS/unhealthy HLS1, with a relative excess risk due to interaction of 0.58 (95% CI: 0.06, 1.10), compared with 2.09% among those with low PRS/healthy HLS1. This pattern was more apparent among those who reported not having received any bowel screening before baseline. Although the observational nature of the study precludes proof of causality, our findings suggest that individuals with a high genetic susceptibility could benefit more substantially than those with a low genetic risk from lifestyle modification in reducing CRC risk.

Genetically predicted physical activity levels are associated with lower colorectal cancer risk: a Mendelian randomisation study

BackgroundWe conducted a Mendelian randomisation (MR) study to investigate whether physical activity (PA) causes a reduction of colorectal cancer risk and to understand the contributions of effects mediated through changes in body fat.MethodsCommon genetic variants associated with self-reported moderate-to-vigorous PA (MVPA), acceleration vector magnitude PA (AMPA) and sedentary time were used as instrumental variables. To control for confounding effects of obesity, we included instrumental variables for body mass index (BMI), body fat percentage, waist circumference and arm, trunk and leg fat ratios. We analysed the effect of these instrumental variables in a colorectal cancer genome-wide association study comprising 31,197 cases and 61,770 controls of European ancestry by applying two-sample and multivariable MR study designs.ResultsWe found decreased colorectal cancer risk for genetically represented measures of MVPA and AMPA that were additional to effects mediated through genetic measures of obesity. Odds ratio and 95% confidence interval (CI) per standard deviation increase in MVPA and AMPA was 0.56 (0.31, 1.01) and 0.60 (0.41, 0.88), respectively. No association has been found between sedentary time and colorectal cancer risk. The proportion of effect mediated through BMI was 2% (95% CI: 0, 14) and 32% (95% CI: 12, 46) for MVPA and AMPA, respectively.ConclusionThese findings provide strong evidence to reinforce public health measures on preventing colorectal cancer that promote PA at a population level regardless of body fatness.

Induction of colitis-associated neoplasia in mice using azoxymethane and dextran sodium sulfate.

Long-standing inflammatory bowel diseases (IBD) increase the risk for the development of colorectal cancer (CRC). This increase is due in large part to chronic intestinal inflammation which exposes the epithelium to pro-carcinogenic factors. Moreover, enhanced mucosal proliferation associated with repetitive wound healing events following an inflammatory episode, further enhance this pro-tumorigenic environment. Although multiple factors involved in IBD pathogenesis and its associated neoplasia have been identified, more work is needed to develop and improve therapies to ameliorate disease and thus reduce CRC risk. Murine models have served as useful tools to identify factors involved in the pathogenesis of colitis-associated neoplasia and test therapies. These include both chemically-induced and genetic engineering approaches, resulting in chronic inflammation and tumor development. Here, we present a step-by-step method of inducing inflammation-associated colon neoplasia by combining administration of azoxymethane and dextran sodium sulfate in mice. A detailed description of this methodology will facilitate its use in the scientific community with the goals of further elucidating the mechanisms underlying colitis-associated tumorigenesis and developing risk reducing interventions.

Is periodontal disease associated with increased risk of colorectal cancer? A meta‐analysis

Colorectal cancer (CRC) is a commonly diagnosed cancer. Previous studies investigating the relationship between periodontal disease (PD) and CRC showed controversial conclusions. This meta-analysis is to explore the association between PD and CRC. Observational studies that explore the association between CRC and PD were included in this meta-analysis. A comprehensive literature search in 7 electronic databases to identify all relevant studies published prior to February 2020. The Newcastle-Ottawa Quality Assessment Scale was used to evaluate the quality each study. The pooled relative risk (RR) and 95% confidence interval (CI) were used to estimate the association between the PD and CRC risk. A total of 838 articles were obtained from database searching and 4 articles were obtained from other sources, and 13 articles with 14 studies involving 634,744 participants were included. An association between PD and increased CRC incidence was found, periodontal disease patients were 21% (95%CI, [1.06, 1.38], I2 =83.9%) more likely to develop colorectal cancer than people with healthy oral cavity. But there is no significant association between PD and CRC mortality. The heterogeneity of this meta-analysis was relatively high, I2 was 83.9% (95%CI, [72.7%, 90.5%]), chi-squared of Q test was 62.18, but sensitivity analysis confirmed the stability of the result. Funnel plot, Egger's test and Begg's test found no publication bias of analysis. The current meta-analysis demonstrates an association between PD and CRC, indicating that early CRC screening is necessary for people with poor oral health, and oral health improvement might be beneficial for reducing CRC risk.

Colon Carcinogenesis: The Interplay Between Diet and Gut Microbiota.

Colorectal cancer (CRC) incidence increases yearly, and is three to four times higher in developed countries compared to developing countries. The well-known risk factors have been attributed to low physical activity, overweight, obesity, dietary consumption including excessive consumption of red processed meats, alcohol, and low dietary fiber content. There is growing evidence of the interplay between diet and gut microbiota in CRC carcinogenesis. Although there appears to be a direct causal role for gut microbes in the development of CRC in some animal models, the link between diet, gut microbes, and colonic carcinogenesis has been established largely as an association rather than as a cause-and-effect relationship. This is especially true for human studies. As essential dietary factors influence CRC risk, the role of proteins, carbohydrates, fat, and their end products are considered as part of the interplay between diet and gut microbiota. The underlying molecular mechanisms of colon carcinogenesis mediated by gut microbiota are also discussed. Human biological responses such as inflammation, oxidative stress, deoxyribonucleic acid (DNA) damage can all influence dysbiosis and consequently CRC carcinogenesis. Dysbiosis could add to CRC risk by shifting the effect of dietary components toward promoting a colonic neoplasm together with interacting with gut microbiota. It follows that dietary intervention and gut microbiota modulation may play a vital role in reducing CRC risk.