Lower Risk Of Colorectal Cancer Research Articles

Chemopreventive Effect of the Germinated Oat and its Phenolic-AVA Extract in Azoxymethane/Dextran Sulfate Sodium (AOM/DSS) Model of Colon Carcinogenesis in Mice.

The consumption of fruits, vegetables, nuts, legumes, and whole grains has been associated with a lower risk of colorectal cancer (CRC) due to the content of natural compounds with antioxidant and anticancer activities. The oat (Avena sativa L.) is a unique source of avenanthramides (AVAs), among other compounds, with chemopreventive effects. In addition, oat germination has shown enhanced nutraceutical and phytochemical properties. Therefore, our objective was to evaluate the chemopreventive effect of the sprouted oat (SO) and its phenolic-AVA extract (AVA) in azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CRC mouse model. Turquesa oat seeds were germinated (five days at 25 °C and 60% relative humidity) and, after 16 weeks of administration, animals in the SO- and AVA-treated groups had a significantly lower inflammation grade and tumor (38–50%) and adenocarcinoma (38–63%) incidence compared to those of the AOM+DSS group (80%). Although both treatments normalized colonic GST and NQO1 activities as well as erythrocyte GSH levels, and significantly reduced cecal and colonic β-GA, thus indicating an improvement in the intestinal parameters, the inflammatory states, and the redox states of the animals, SO exerted a superior chemopreventive effect, probably due to the synergistic effects of multiple compounds. Our results indicate that oats retain their biological properties even after the germination process.

Adherence to the Dietary Approaches to Stop Hypertension (DASH) dietary pattern reduces the risk of colorectal cancer: A systematic review and meta-analysis

Colorectal cancer (CRC) has become a major concern due to industrialization and dietary changes generated by it. Many of the components of the DASH (Dietary Approach to Stop Hypertension) diet are associated with the risk of CRC. However, the relationship between DASH dietary pattern and CRC has not been studied yet in a systematic review and meta-analysis. The present study was conducted to review the studies investigating the relationship between DASH diet and the risk of CRC. PubMed and Scopus search engines were searched to find relevant publications from inception up to September 2019. All the observational studies that addressed the association between DASH diet and CRC were included in the systematic review and meta-analysis. All the steps including data base search, screening, and data extraction were carried out by two researchers, independently. Eight studies included in this systematic review and 5 studies (out of 8 studies included in the systematic review) were included in the meta-analysis. Combining 12 effects sizes from 5 studies, a significant inverse association between adherence to the DASH diet and risk of CRC was found (RR: 0.80; 95% CI: 0.74, 0.85). Based on the result of this study, individuals with greater adherence to DASH diet had 20% lower risk of CRC. The current study demonstrates that the risk of CRC is negatively associated with the adherence to the DASH dietary pattern.

Intake or Blood Levels of n-3 Polyunsaturated Fatty Acids and Risk of Colorectal Cancer: A Systematic Review and Meta-analysis of Prospective Studies.

Previous results of the association between n-3 polyunsaturated fatty acids (PUFA) and colorectal cancer were inconsistent. We conducted a systematic review and meta-analysis of prospective studies. The PubMed and Embase databases were searched through July 10, 2019, followed by a manual search. A random-effects model was used. Twenty prospective studies, including 18,102 cases and 1,360,046 participants, were included. The pooled RR of colorectal cancer for the highest versus lowest category of n-3 PUFA intake was 0.97 [95% confidence interval (CI), 0.90-1.04]. Regarding the type of n-3 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intakes were inversely associated with 11% (RR = 0.89; 95% CI, 0.80-0.99) and 12% (RR = 0.88; 95% CI, 0.81-0.96) lower colorectal cancer risks, respectively, in the comparison of the highest versus lowest category. Increments of 0.1 g/day of EPA (RR = 0.95; 95% CI, 0.92-0.98) and DHA (RR = 0.97; 95% CI, 0.95-0.99) intakes were associated with a lower colorectal cancer risk. Regarding the blood levels of n-3 PUFAs, the pooled RR of colorectal cancer for the highest versus lowest category of blood levels of n-3 PUFAs was 0.79 (95% CI, 0.64-0.98). The risk of colorectal cancer decreased by 4% for every 1% increase in blood n-3 PUFA levels (RR = 0.96; 95% CI, 0.92-1.00). High blood n-3 PUFA levels are inversely associated with colorectal cancer risk, and high n-3 PUFA intake is suggestively associated with lower colorectal cancer risk. Our findings suggest that high blood n-3 PUFA levels may be associated with reduced colorectal cancer risk, but further studies are needed.

A prospective cohort analysis of gut microbial co-metabolism in Alaska Native and rural African people at high and low risk of colorectal cancer

Alaska Native (AN) people have the world's highest recorded incidence of sporadic colorectal cancer (CRC) (∼91:100,000), whereas rural African (RA) people have the lowest risk (<5:100,000). Previous data supported the hypothesis that diet affected CRC risk through its effects on the colonic microbiota that produce tumor-suppressive or -promoting metabolites. We investigated whether differences in these metabolites may contribute to the high risk of CRC in AN people. A cross-sectional observational study assessed dietary intake from 32 AN and 21 RA healthy middle-aged volunteers before screening colonoscopy. Analysis of fecal microbiota composition by 16S ribosomal RNA gene sequencing and fecal/urinary metabolites by 1H-NMR spectroscopy was complemented with targeted quantification of fecal SCFAs, bile acids, and functional microbial genes. Adenomatous polyps were detected in 16 of 32 AN participants, but not found in RA participants. The AN diet contained higher proportions of fat and animal protein and less fiber. AN fecal microbiota showed a compositional predominance of Blautia and Lachnoclostridium, higher microbial capacity for bile acid conversion, and low abundance of some species involved in saccharolytic fermentation (e.g., Prevotellaceae, Ruminococcaceae), but no significant lack of butyrogenic bacteria. Significantly lower concentrations of tumor-suppressive butyrate (22.5±3.1 compared with 47.2±7.3 SEM µmol/g) coincided with significantly higher concentrations of tumor-promoting deoxycholic acid (26.7±4.2 compared with 11±1.9 µmol/g) in AN fecal samples. AN participants had lower quantities of fecal/urinary metabolites than RA participants and metabolite profiles correlated with the abundance of distinct microbial genera in feces. The main microbial and metabolic CRC-associated markers were not significantly altered in AN participants with adenomatous polyps. The low-fiber, high-fat diet of AN people and exposure to carcinogens derived from diet or environment are associated with a tumor-promoting colonic milieu as reflected by the high rates of adenomatous polyps in AN participants.

Postmenopausal hormone replacement therapy and colorectal cancer risk by molecular subtypes and pathways.

Postmenopausal hormone replacement therapy (HRT) was found to be associated with lower risk of colorectal cancer (CRC). However, little is known regarding associations with molecular subtypes of CRC. The current study includes female participants of a large German population-based case-control study (922 CRC cases and 1,183 controls). Tumor tissue samples were analyzed for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), BRAF and KRAS mutation status. Multivariable logistic regression models were used to assess the association of HRT use with molecular subtypes and pathways. Postmenopausal HRT use was overall associated with reduced risk of CRC (adjusted odds ratio (aOR) 0.62, 95% confidence interval (CI) 0.50-0.76) and no major differences were observed for molecular subtypes or for tumor marker combinations representing molecular pathways. When stratified by median age (≤/>71 years) potentially stronger risk reductions were observed in the older group for subtypes showing MSI (OR = 0.36, 95% CI 0.17-0.76), BRAF mutation (OR = 0.40, 95% CI 0.30-0.83) and CIMP-high (OR = 0.40, 95% CI 0.21-0.73) and for CRC suggestive of the sessile serrated pathway (OR = 0.45, 95% CI 0.20-1.01). In conclusion, postmenopausal use of HRT was similarly associated with risk reduction of major molecular tumor subtypes and pathways of CRC. Potentially stronger risk reductions with CRC subtypes diagnosed at higher ages require confirmation and clarification from other studies. The current study extends the limited understanding of the mechanisms of HRT in CRC prevention.

Relatively low risk and nonaggressive stage of colorectal cancer in individuals with negative baseline fecal immunochemical test results: A cohort study

AbstractFecal immunochemical testing (FIT) is used as a screening tool because of its adequate sensitivity to detect colorectal cancer (CRC). Whether individuals with negative baseline FIT results have a low risk of CRC over a long period of follow‐up remains unclear. This retrospective cohort study investigated the characteristics of CRC in individuals with normal baseline FIT results. We retrospectively evaluated individuals who participated in the Taiwanese biennial FIT‐based CRC screening program at a single hospital between March 2010 and December 2017. Patients who had positive FIT results (≥30 μg Hb/g feces) and then underwent confirmatory colonoscopy were enrolled for further analysis. Patients were divided into two cohorts: target group (consisting of patients with negative FIT results in the baseline round, followed by positive FIT results and confirmatory colonoscopy in any one of the subsequent rounds) and reference group (consisting of patients with positive FIT results in the baseline round and confirmatory colonoscopy). The detection rate and characteristics of CRC were compared between two groups. A P value of &lt;.05 was considered statistically significant. A total of 51 789 individuals underwent 80 195 tests in four rounds of biennial FIT based CRC screening. The positivity rate of FIT was 8.2% (n = 6591). The colonoscopy compliance rate was 70.3% (n = 4635). From 4635 individuals, 1650 and 2985 were included in the target and reference groups, respectively. The CRC detection rate in the target and reference groups was 2.3% (38/1650) and 5.0% (149/2985), respectively (odds ratio = 0.45; 95% confidence interval = 0.31‐0.64). The CRC detection rate in the target group increased with screening intervals (P for trend = .001). After excluding patients with unknown stage, 35 patients in the target group and 130 patients in the reference group were included for subsequent analysis. Lesions were located mainly in the distal colon in both groups (82.9% [29/35] vs. 82.3% [107/130]; P = 1). The distribution of the CRC stage according to the seventh edition of the American Joint Committee on Cancer staging system in the target vs reference group was as follows: Stage 0: 48.6% vs 20.0%; Stage I: 11.4% vs 30.0%; Stage II: 20.0% vs 18.5%; Stage III: 17.1% vs 22.3%; and Stage IV: 2.9% vs 9.2%; (P = .008). CRC detection rate declined considerably if the baseline FIT result was negative. CRC detected in patients with negative baseline FIT results showed a high proportion of nonaggressive stage. Approximately 80% of CRCs were identified in the left‐sided colon, suggesting the limited ability of repetitive FIT to detect proximal CRC. These results support the benefits and necessity of consecutive FIT screening even when the baseline FIT result is negative.

Associations between dietary vitamin D, calcium and dairy products intakes and colorectal cancer risk: a case-control study in China

AbstractIntroductionThe effect of dietary vitamin D, calcium and dairy products intake on colorectal cancer risk is controversial. This study aims to investigate the associations between dietary vitamin D, calcium, dairy products intake and colorectal cancer risk among Chinese population.Materials and MethodsDuring July 2010 to December 2018, 2380 incident, first primary, histologically confirmed colorectal cancer cases and 2389 sex and age-matched (5-year interval) controls were recruited. Dietary intake information was collected by face-to-face interviews using a validated food frequency questionnaire. Energy and other nutrient intakes such as dietary calcium were computed on the basis of the 2002 Chinese Food Composition Table, and the dietary vitamin D intake was calculated according to the United States Department of Agriculture Food Composition Database. Unconditional multivariable logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence interval (CI) after adjusting for various confounders, including socio-demographic characteristics, lifestyle factors, BMI, family history of cancer, energy intake and several nutrient intakes.ResultsThe energy-adjusted mean dietary vitamin D, calcium and total dairy products intakes were 5.69μg/d, 406.94mg/d, 4.02g/d for cases and 6.81μg/d, 468.21mg/d, 9.50g/d for controls. Compared with the controls, cases had a lower intake of dietary vitamin D, calcium and total dairy (P &lt; 0.001). A higher intake of dietary vitamin D and calcium was found to be associated with 43% and 51% reduction in colorectal cancer. The ORs of the highest quartile compared with the lowest quartile intake were 0.57 (95% CI: 0.46, 0.70, Ptrend &lt; 0.001) for dietary vitamin D and 0.49 (95% CI: 0.39, 0.61, Ptrend &lt; 0.001) for dietary calcium. We observed a statistically significant inverse association of dairy products intake with colorectal cancer risk. Compared with the lowest tertile, the adjusted ORs for the highest tertile were 0.31 (95% CI: 0.26, 0.38, Ptrend &lt; 0.001) for total dairy. The inverse associations of dietary vitamin D, calcium and dairy products intakes with colorectal cancer risk were observed in both men and women, colon and rectal cancer.ConclusionOur study indicated that higher dietary vitamin D, calcium and dairy products intakes were associated with a lower colorectal cancer risk.

TaqI and ApaI Variants of Vitamin D Receptor Gene Increase the Risk of Colorectal Cancer in a Saudi Population.

Background:Polymorphisms in the gene encoding the vitamin D receptor (VDR) affect the protective role of vitamin D against many types of cancers, including colorectal cancer (CRC).Objective:The objective of this study was to assess the effect of four major polymorphisms of the VDR gene (ApaI, TaqI, BsmI and FokI) on the risk of CRC in a Saudi population.Materials and Methods:This case–control study recruited 132 CRC patients from the oncology clinics at King Abdulaziz University Hospital and 124 healthy controls from the blood bank at King Fahad General Hospital, Jeddah, Saudi Arabia, between September 2017 and August 2018. All participants were Saudis and aged 20–80 years. Genomic DNA samples were extracted from the peripheral blood cells and amplified with polymerase chain reaction. The resulting fragments were digested with different endonucleases to reveal the genotypes using the restriction fragment length polymorphism technique. The genotype distribution and allele frequency, odds ratio (OR), risk ratio (RR) and P values were determined with contingency table analysis following Hardy–Weinberg equilibrium equation.Results:For the ApaI single-nucleotide polymorphism (SNP) (rs7975232), only the heterozygous (Aa) genotype increased the risk of CRC (OR = 3.4, RR = 2.3, and P < 0.0001), whereas the TaqI SNP (rs731236) carriers with either the heterozygous (Tt) or homozygous (tt) genotype displayed an increased risk for the disease (OR = 6.18, RR = 4, P < 0.0001; OR = 3, RR = 2.4, P = 0.02, respectively). In contrast, heterozygous (Bb) and homozygous (bb) carriers of the BsmI SNP (rs1544410) had significantly lower risk for CRC (P < 0.0001). Finally, for the FokI SNP (rs2228570), there was no association with CRC risk.Conclusion:This study found that VDR SNPs ApaI and TaqI increase the risk of CRC, whereas BsmI reduces the risk of CRC in the selected Saudi population. Therefore, ApaI and TaqI SNPs could potentially be used as a diagnostic biomarker for CRC. However, the molecular mechanisms by which these variants increase or decrease the risk of CRC need to be investigated.

Association of change in the neighborhood obesogenic environment with colorectal cancer risk: The Multiethnic Cohort Study.

BackgroundNeighborhood environment has been associated with health behaviors. Despite the evidence of the influence of neighborhood social and physical factors on cancer risk, no research has evaluated whether changes in the neighborhood obesogenic environment, either by physical moves to different neighborhoods or experiencing neighborhood redevelopment or neglect, affect cancer risk.MethodsThe association of change in neighborhood environment attributes (socioeconomic status, population density, restaurant and retail food environments, numbers of recreational facilities and businesses, commute patterns, traffic density, and street connectivity) with colorectal cancer (CRC) risk was examined among 95,472 Los Angeles, CA, Multiethnic Cohort participants, including 2295 invasive CRC cases diagnosed between 1993 and 2010 using Cox proportional hazards regression, adjusting for age, race/ethnicity, other risk factors including BMI and physical activity, and baseline levels of neighborhood attributes. Stratified analyses were conducted by racial/ethnic group and moving status.Results40% of participants moved (changed physical residence) during follow-up. Across all races/ethnicities, upward change in population density was statistically significantly associated with higher CRC risk among male and female non-movers (HR: 1.35 and 1.41, respectively). The same association was also observed separately among female African American and Japanese American non-movers, male Latino non-movers, female African American and male White movers. Downward change in population density was significantly related to higher CRC risk among female non-movers (HR: 1.33). Downward change in traffic density was associated with lower CRC risk among male non-movers but with higher CRC risk among female movers (HR: 0.66 and 1.43, respectively). Downward changes in street connectivity or the number of recreational facilities were associated with higher CRC risk (HR: 1.34 and 1.54, respectively). Upward change in the number of recreational facilities was associated with lower CRC risk among female non-movers (HR: 0.70). Changes in the other neighborhood attributes did not exhibit significant associations with CRC risk within more than one racial/ethnic group.ConclusionChanges over time in neighborhood attributes have an effect on the risk of colorectal cancer, which is separate from the baseline levels of the same attributes and individual-level risk factors, and differs between sexes, movers and non-movers and across racial/ethnic groups.

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.

The diagnostic accuracy of the faecal immunochemical test for colorectal cancer in risk-stratified symptomatic patients.

The faecal immunochemical test detects blood in the faeces, reporting faecal haemoglobin quantitatively in micrograms of haemoglobin per gram of faeces. The aim of this pilot study was to determine the feasibility of using the faecal immunochemical test as a rule-out test in symptomatic patients at low and high risk of colorectal cancer. Between November 2016 and October 2017, consecutive symptomatic patients within a multicultural part of London were recruited to perform a faecal immunochemical test prior to colonoscopy. Analysis was performed on the HM-JACKarc analyser. Faecal immunochemical test samples were returned by 298 patients who underwent colonoscopy. There was no significant variation in faecal haemoglobin levels by age, sex, ethnicity or deprivation. The overall detection rate for colorectal cancer was 100% at 2 µg/g and 92% at 10 µg/g. If a faecal haemoglobin threshold for investigation of 2 µg/g (ie detectable) or 10 µg/g had been employed, the number of colonoscopies would have been reduced by 70% and 84%, respectively, in all symptomatic patients. For low-risk patients, the sensitivity of the faecal immunochemical test for colorectal cancer at both thresholds of 2 µg/g or 10 µg/g remained 100%, with the number of colonoscopies reduced by 80% and 91%, respectively. This study shows that the faecal immunochemical test is a promising technology that detected colorectal cancer in all high- or low-risk symptomatic patients in our cohort at a threshold of detectable faecal haemoglobin. Data from adequately powered cohort studies will elucidate the true diagnostic accuracy of the test and the rate and patterns of undetected colorectal cancer.

A colorectal cancer diet quality index is inversely associated with colorectal cancer in the Malmö diet and cancer study.

The World Cancer Research Fund International has concluded strong evidence for that high intake of dairy products and foods containing dietary fiber and low intake of processed meat are associated with decreased risk of colorectal cancer (CRC). As food items are consumed together, it is important to study dietary patterns. The aim of the present study was to examine the association between an a priori constructed dietary index and incident CRC and between intake of processed meat, fiber, and dairy products and CRC. In the Malmö Diet and Cancer study cohort, 923 cases of CRC were identified, during 502 136 person-years of follow-up. A Colorectal Diet Quality Index (CDQI) was constructed regarding intakes of processed meat, fiber, and dairy products in relation to CRC. Higher index indicated a higher dietary quality. Higher CDQI was associated with lower risk of CRC [hazard ratios (HR): 0.57 for highest compared with lowest quintile; 95% confidence interval (CI): 0.43, 0.75; P<0.001]. Intake of dairy products was inversely associated with risk of CRC [HR for highest vs. lowest quintile was 0.77 (CI: 0.62, 0.96); P = 0.008], as was dietary fiber [HR for highest vs. lowest quintile was 0.77 (CI: 0.61, 0.98); P = 0.043]. High intake of processed meat was associated with CRC [HR for highest vs. lowest quintile was 1.31; CI: 1.05, 1.63; P = 0.012]. High adherence to a predefined CRC-specific diet quality index was inversely associated with the risk of CRC and gave a stronger association with CRC, than when analyzing the components of the CDQI individually.

Association of Circulating Vitamin D With Colorectal Cancer Depends on Vitamin D-Binding Protein Isoforms: A Pooled, Nested, Case-Control Study.

BackgroundHigher circulating 25-hydroxyvitamin-D [25(OH)D] concentrations are consistently inversely associated with colorectal cancer (CRC) risk in observational studies. However, it is unknown whether this association depends on the functional GC-rs4588*A (Thr436Lys) variant encoding the vitamin D–binding protein-2 (DBP2) isoform, which may affect vitamin D status and bioavailability.MethodsWe analyzed data from 1710 incident CRC cases and 1649 incidence-density–matched controls nested within three prospective cohorts of mostly Caucasians. Study-specific incidence rate ratios (RRs) for associations of prediagnostic, season-standardized 25(OH)D concentrations according to DBP2 isoform with CRC were estimated using multivariable unconditional logistic regression and were pooled using fixed-effects models. All statistical significance tests were two-sided.ResultsThe odds of having 25(OH)D concentrations less than 50 nmol/L (considered insufficient by the Institute of Medicine) were 43% higher for each DBP2-encoding variant (rs4588*A) inherited (per DBP2 odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.27 to 1.62, Ptrend = 1.2 × 10−8). The association of 25(OH)D concentrations with CRC risk differed by DBP2: 25(OH)D concentrations considered sufficient (≥ 50 nmol/L), relative to deficient (< 30 nmol/L), were associated with a 53% lower CRC risk among individuals with the DBP2 isoform (RR = 0.47, 95% CI = 0.33 to 0.67), but with a non–statistically significant 12% lower risk among individuals without it (RR = 0.88, 95% CI = 0.61 to 1.27) (Pheterogeneity = .01).ConclusionsOur results suggest that the 25(OH)D-CRC association may differ by DBP isoform, and those with a DBP2-encoding genotype linked to vitamin D insufficiency may particularly benefit from adequate 25(OH)D for CRC prevention.

Does Colon Polyp Surveillance Improve Patient Outcomes?

Colon polyp surveillance now accounts for 25% of all colonoscopies performed. The evidence that colonoscopy surveillance reduces colorectal cancer (CRC) incidence or mortality is weak. The biology of the baseline lesions and quality of the baseline exam are two primary factors contributing to post-colonoscopy CRC. Prior recommendations for surveillance were based largely on the likelihood that patients with adenomas would develop advanced adenomas, a surrogate for CRC. There is now evidence that baseline colonoscopy findings are strongly associated with the risk of incidence or death from CRC. This evidence provides a basis for updated evidence-based recommendations for surveillance. In addition, there is also growing evidence that the quality of the baseline exam is an important predictor of the likelihood of developing post-colonoscopy CRC.

Comparative evaluation of colonoscopy, fecal immunochemical test, and a novel risk-adapted approach for colorectal cancer screening: preliminary baseline results of a multicentre randomised controlled trial (Target-C)

BackgroundFor colorectal cancer (CRC) screening, the use of risk prediction models to identify potential high-risk populations and implementation of appropriate risk-adapted screening may be more cost-effective than traditional screening strategies. However, evidence from randomised controlled trials is lacking. This study aimed to evaluate colonoscopy, fecal immunochemical test (FIT) and a novel risk-adapted screening approach in a large-scale multicentre randomised controlled trial in China. MethodsThis ongoing trial has been conducted in six study centres in five provinces in China since May 2018. People aged 50–74 years living in the study areas were approached to assess eligibility. Overall, 19 582 eligible participants were enrolled from May, 2018, to May, 2019. After providing signed informed consent, participants were randomly assigned to one of three screening groups, with a 1:2:2 ratio: (1) one-time colonoscopy (n=3937); (2) annual fecal immunochemical test (FIT; n=7858); and (3) annual risk-adapted screening strategy (n=7787). The risk-adapted screening strategy used an established CRC risk scoring system, the Asia-Pacific Colorectal Screening Score. Participants at high risk of CRC were referred for colonoscopy, whereas participants at low risk of CRC were referred for a FIT. Participants with positive FIT results were also referred for diagnostic colonoscopy. Information on clinical reports and epidemiological risk factors were collected and stored in a web-based data system. The primary outcome was detection rate of advanced colorectal neoplasia and secondary outcomes included rate of adherence to the study protocol, compliance rate of colonoscopy, detection rate of any neoplasm, complication rate, and the rate of mortality. A 4-year screening phase (with 1-year baseline screening and 3 years of follow-up screening) will be conducted for all participants and a subsequent 6-year active and passive follow-up phase will be implemented. Here we present the preliminary baseline screening results. This study was approved by the Ethics Committee of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (18-013/1615) and the protocol was registered in the Chinese Clinical Trial Registry (identifier: ChiCTR1800015506). FindingsAfter we excluded 36 participants who did not meet the inclusion criteria after further evaluation, 19 546 participants were included for the primary analysis (3916 colonoscopy, 7854 FIT, and 7776 risk-adapted screening). Mean age was 60·5 (SD 6·5) years and 41·7% (8154 of 19 546) were men. No statistically significant differences for age and sex distribution were observed between the groups. Participation rates were 42·5% (1665 of 3916) for colonoscopy, 94·0% (7386 of 7854) for FIT, and 85·2% (6628 of 7776) for risk-adapted screening. Of the participants assessed to be at high risk of CRC in the risk-adapted group (18·9%, 1472 of 7776), 49·2% (724 of 1472) accepted colonoscopy screening, a significantly higher proportion than in the colonoscopy group (42·5%; p<0·05). Of participants assessed to be at low risk of CRC in the risk-adapted screening group (80·7%, 6279 of 7776), 94·0% (5904 of 6279) accepted FIT screening, similar to the rate in the FIT group (94·0%). The overall positivity rate of FIT was 14·3%, and over 85% of participants with positive FIT results undertook subsequent diagnostic colonoscopy. For the intention-to-screen analysis, detection rates for advanced colorectal neoplasms were 2·93% for colonoscopy, 1·29% for FIT and 1·83% for risk-adapted screening. The FIT and the risk-adapted screening groups had lower numbers of colonoscopies needed to detect one advanced neoplasm than the colonoscopy group (eight, ten, and 15 colonoscopies, respectively). InterpretationThis is the first large-scale population-based trial in China to compare effectiveness of three different colorectal cancer screening strategies targeting adults aged 50–74 years. For the interim analysis of the baseline screening in this trial, the FIT and the novel risk-adapted screening approach had higher participation rates than the colonoscopy screening approach, and they required fewer numbers of colonoscopies to detect one advanced neoplasm, indicating the feasibility and effectiveness of these two approaches in population-based CRC screening. The findings of this study may provide timely evidence in designing effective population-based CRC screening strategies. FundingThis study was sponsored by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2017-I2M-1-006) and the National Natural Science Foundation of China (81703309).

245 Dietary Calcium and Vitamin D Intake and Colonic Mucosa-Associated Microbiome in Healthy Individuals

INTRODUCTION: Studies have demonstrated antitumor or anti-inflammatory properties of calcium and vitamin D. Dietary calcium and vitamin D intake has been associated with lower risk of colorectal cancer. However, the effect of calcium and vitamin D intake on gut microbiota is not well understood. METHODS: This is a cross-sectional study of 99 colonic biopsies of 35 individuals (average age 62 years, 77% Caucasian and 1 woman) with poly-free colonoscopy between August 2013 and April 2017 at Michael E. DeBakey VA Medical Center. Microbial DNA was isolated and the V4 region of the16S rRNA gene was amplified then sequenced for microbiome profiling. A food frequency questionnaire was used to ascertain calorie-adjusted calcium and vitamin D intake. Median intake was used to dichotomize the intake to low vs. high. Sequencing data were analyzed using the UPARSE and SILVA database for operational taxonomic unit (OTU) classification. Alpha-diversity (Shannon index), beta-diversity (weighted UniFrac) and relative abundance of bacteria (Mann-Whitney test) were compared between low vs. high intake. Reported P-value was adjusted for multiple comparisons using false discovery rate (FDR). RESULTS: Compared with lower intake, higher dietary calcium and vitamin D intakes were both associated with greater richness and evenness (P value &lt; 0.005). The community composition also differed by calcium and vitamin D intake (P = 0.001). In phylum level, the relative abundance of Verrucomicrobia was greater in individuals with higher calcium and vitamin D intake (P values &lt; 0.005). In genus level, high consumption of both calcium and vitamin D were associated with a significantly higher relative abundance of Akkermansia, Faecalibacterium, Dialister, Haemophilus, Odoribacter, Fusicatenibacter, and Paraprevotella, but a lower abundance of Erysipelatoclostridium and Lachnoclostridium (FDR P values &lt; 0.05). Higher intake of calcium, but not vitamin D, was also associated with lower abundance of Bacteroides and higher abundance of Parabacteroides (P values = 0.02). CONCLUSION: Higher intake of calcium and vitamin D was associated with a higher diversity of colonic microbiota and higher abundance of potentially beneficial bacteria and lower abundance of harmful bacteria in healthy individuals. Further metagenomics and metabolomics research are needed to understand whether and how the protective effect of calcium and vitamin D on colorectal cancer is partially mediated through gut microbiome.

Prediction of risk scores for colorectal cancer patients from the concentration of proteins involved in mitochondrial apoptotic pathway.

One of the major challenges in managing the treatment of colorectal cancer (CRC) patients is to predict risk scores or level of risk for CRC patients. In past, several biomarkers, based on concentration of proteins involved in type-2/intrinsic/mitochondrial apoptotic pathway, have been identified for prognosis of colorectal cancer patients. Recently, a prognostic tool DR_MOMP has been developed that can discriminate high and low risk CRC patients with reasonably high accuracy (Hazard Ratio, HR = 5.24 and p-value = 0.0031). This prognostic tool showed an accuracy of 59.7% when used to predict favorable/unfavorable survival outcomes. In this study, we developed knowledge based models for predicting risk scores of CRC patients. Models were trained and evaluated on 134 stage III CRC patients. Firstly, we developed multiple linear regression based models using different techniques and achieved a maximum HR value of 6.34 with p-value = 0.0032 for a model developed using LassoLars technique. Secondly, models were developed using a parameter optimization technique and achieved a maximum HR value of 38.13 with p-value 0.0006. We also predicted favorable/unfavorable survival outcomes and achieved maximum prediction accuracy value of 71.64%. A further enhancement in the performance was observed if clinical factors are added to this model. Addition of age as a variable to the model improved the HR to 40.11 with p-value as 0.0003 and also boosted the accuracy to 73.13%. The performance of our models were evaluated using five-fold cross-validation technique. For providing service to the community we also developed a web server ‘CRCRpred’, to predict risk scores of CRC patients, which is freely available at https://webs.iiitd.edu.in/raghava/crcrpred.

Effects of Colorectal Cancer Risk Factors on the Association Between Aspirin and Colorectal Cancer.

We investigated the effect of aspirin on colorectal cancer (CRC) risk among subgroups of women with and without risk factors for CRC. Using data from the Women's Health Initiative, we estimated hazard ratios for CRC in association with aspirin use, with stratifications by cardiovascular disease (CVD) risk status, family history of CRC, and history of colorectal polypectomy. Aspirin was associated with a lower risk of CRC among women with low/normal or high CVD-risk status; no family history of CRC; or a history of colonoscopy with polypectomy. Aspirin was not associated with CRC among women with a family history of CRC or a history of colonoscopy without polypectomy. Aspirin was associated with a lower risk of CRC in women at all levels of CVD-risk, in those with a history of colonoscopy with polypectomy, and in those without a family history of CRC.

Adherence to the World Cancer Research Fund/American Institute for Cancer Research 2018 Recommendations for Cancer Prevention and Risk of Colorectal Cancer.

The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) 2018 diet, nutrition, and physical activity recommendations aim to reduce cancer risk. We examined adherence to the WCRF/AICR recommendations and colorectal cancer risk in two prospective cohorts. We followed 68,977 women in the Nurses' Health Study and 45,442 men in the Health Professionals Follow-up Study from 1986 until 2012. We created cumulatively averaged WCRF/AICR scores using updated diet, adiposity, and physical activity data from questionnaires, and used Cox regression to estimate sex-specific HRs and 95% confidence intervals (CI) for incident colorectal cancer. We documented 2,449 colorectal cancer cases. Men in the highest quintile of the WCRF/AICR lifestyle score had a lower risk of colorectal cancer compared with those in the lowest quintile (HRQ5vsQ1 = 0.64; 95% CI, 0.52-0.77). The result was weaker in women (HRQ5vsQ1 = 0.86; 95% CI, 0.72-1.02; P heterogeneity by sex = 0.006). When analyzing the diet recommendations alone, we similarly observed stronger inverse associations in men (HRQ5vsQ1 = 0.74; 95% CI, 0.61-0.90) compared with women (HRQ5vsQ1 = 0.93; 95% CI, 0.77-1.12; P heterogeneity by sex = 0.06). In men, the lifestyle score was more strongly inversely associated with risk of distal colon cancer compared with proximal colon or rectal cancer (P common effects = 0.03); we did not observe significant differences between anatomic locations in women. The 2018 WCRF/AICR cancer prevention recommendations are associated with lower colorectal cancer risk in men, with weaker results in women. Consideration of adiposity and physical activity in conjunction with diet is important for colorectal cancer prevention.

Highlights of This Issue

Increasingly, research studies have found higher burden of most cancers in rural areas compared to urban areas. Examining these patterns at smaller geographic units (e.g., census tracts instead of counties) can increase the precision of these findings, but patient privacy must be maintained. Moss and colleagues demonstrated that adding two census tract-level rurality variables to NCI SEER does not appreciably increase the risk of deductive disclosure, but does support novel analyses for surveillance and etiologic research on geographic disparities in cancer. Interested researchers can request access to this database to study urban/rural differences in cancer incidence and survival.Adolescents and young adults (AYAs, age 15-39 years) with cancer represent an understudied patient population in the U.S. Using population-based data, Anderson and colleagues investigated factors associated with mortality from noncancer causes after an AYA cancer diagnosis, with a focus on disparities related to race/ethnicity, county-level socioeconomic status indicators, geographic region, and rural-urban continuum. Results suggest that the risk of noncancer mortality after AYA cancer is highest among survivors who are non-Hispanic Black or live in the South or in rural counties. Further research is needed to better understand the specific factors underlying the risk of poor outcomes in these groups.Given limited available data, Rostron and colleagues assessed the relationship between biomarkers of exposure (BOE) and cigarettes per day (CPD) in over 2700 adult daily cigarette smokers in Wave 1 of the PATH Study. Among exclusive cigarette smokers, dual cigarette and e-cigarette users, and dual cigarette and smokeless tobacco users, biomarker concentrations consistently increased with CPD, although they often leveled off at high smoking levels. Dual users were exposed to higher levels of certain toxicants than exclusive cigarette smokers. Thus, while BOE display a dose-response relationship with CPD, the relationship may not be linear, and smokers of few CPD receive appreciable levels of exposure.In 2018, the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) released updated recommendations on diet, adiposity, and physical activity for cancer prevention. Petimar and colleagues developed a score that measures adherence to these recommendations and examined associations of this score with incident colorectal cancer among 114,419 participants of the Nurses' Health Study and Health Professionals Follow-up Study. Greater adherence to the 2018 WCRF/AICR recommendations was associated with lower colorectal cancer risk, with stronger results in men than women. These results support the hypothesis that a high-quality diet, healthy weight, and physical activity are important for colorectal cancer prevention.