Colorectal Cancer Prevention Strategies Research Articles

Association of dietary fiber intake and gut microbiota in healthy adults.

1569 Background: Increasing evidence has shown that gut microbiota alterations may play a role in colorectal cancer risk. Diet, particularly fiber intake, may modify gut microbiota composition, which may consequently impact cancer risk development. We investigated the relationship between dietary fiber intake and gut microbiota in healthy humans. Methods: Using 16S rRNA gene sequencing, we assessed gut microbiota in fecal samples from 151 healthy adults in two independent study populations: Study A, n = 75 (healthy controls from a colorectal cancer case-control study), and Study B, n = 76 (polyp-free subjects from a cross-sectional colonoscopy study). We calculated energy-adjusted total dietary fiber intake of participants based on food frequency questionnaires. For each study population, we evaluated the relationship between quartiles of higher fiber intake as a continuous ordinal variable, and global gut microbiota community composition (via PERMANOVA of weighted UniFrac distance) and specific taxon abundance (via DESeq2). Results: We found that fiber intake was significantly associated with overall microbial community composition in Study B (p = 0.003) but not Study A (p = 0.68), after adjustment for age, sex, race, body mass index, and cigarette smoking. In a taxonomy-based meta-analysis of these two study populations, higher fiber intake was associated with lower abundance of genus Actinomyces (fold change [FC] = 0.769, p = 0.003), and higher abundance of genera Faecalibacterium (FC = 1.153, p = 0.03), Lachnospira (FC = 1.167, p = 0.04), and SMB53 (FC = 1.201, p = 0.05). A species-level meta-analysis showed an association between higher fiber intake and higher abundance of Faecalibacterium prausnitzii (FC = 1.165, p = 0.03) and lower abundance of Ruminococcus bromii (FC = 0.828, p = 0.08). Conclusions: Our results suggest that higher intake of dietary fiber may alter gut microbiota in healthy adults. Given the potentially modifiable nature of the gut microbiota through diet, these findings warrant further study of diet-microbiota based colorectal cancer prevention strategies.

Clinicopathologic distribution of KRAS and BRAF mutations in a Chinese population with colorectal cancer precursor lesions.

Investigating the clinical features and corresponding histomorphologic and molecular profiles of precursor lesions of colorectal cancer in a natural population provides new insights into the nature of colorectal cancer, uncovers new screening markers and establishes new prevention strategies for colorectal cancer. In this study, 4302 patients with at least one colorectal polyp from a large colorectal cancer screening program were evaluated and genetic mutations in either KRAS or BRAF were detected in 495 patients. The population-based mutation rates of KRAS and BRAF genes in colorectal polyps within this Chinese patient population were 21.8% and 12.1% respectively. Interestingly, considerable variability in the KRAS and BRAF mutations rates were found among different types of polyps. In a multivariate analysis, presence of villous histology and high-grade dysplasia was associated with KRAS mutations (OR, 3.0; 95% CI, 1.7-5.4 and OR, 3.5; 95% CI 1.9-6.5, respectively), while serrated adenomas and hyperplastic polyps were associated with BRAF V600E mutations (OR, 20.6; 95% CI, 8.2–51.8 and OR, 11.9; 95% CI 4.9–29.0, respectively). KRAS mutations may, in part, drive the histologic progression of adenomas toward a villous histology and higher grades of dysplasia. Mutant BRAF may, in part, drive the histologic progression of adenomas toward serrated histology. Dysplasia may arise from hyperplastic polyps, resulting in the formation of serrated adenomas and potentially the development of colorectal carcinoma.

Abstract A21: A Phase IIa trial of metformin for colorectal cancer risk reduction among patients with a history of colorectal adenomas and elevated body mass index

Abstract Background: Despite advances in colorectal cancer (CRC) screening, early detection, and treatment, CRC remains the 2nd most common cancer cause of death in the U.S.. Obesity is increasing in incidence in the U.S., and has been implicated in colorectal adenoma (CRA) risk, risk of CRA recurrence, and risk of CRC. Obese patients with history of CRA are a high-risk group that may benefit from novel CRC prevention strategies. There is early evidence for reduced cancer mortality among metformin users. The signaling pathway activated by metformin (LKB1/AMPK/mTOR) is implicated in tumor suppression in ApcMin/+ mice, as evidenced by metformin-induced reduction in polyp burden, increased ratio of pAMPK/AMPk, decreased ratio of pmTOR/mTOR, and decreased ratio of pS6Ser235/S6Ser235 in polyp specimens. We hypothesized that metformin would affect colorectal tissue S6Ser235 similarly in humans, targeting obese patients with recent history of CRAs as a high-risk group. Methods: A phase IIa clinical biomarker trial was conducted across 3 clinical sites via the NCI-funded Southern California Chemoprevention Program. Eligible participants included non-diabetic, obese patients (BMI >30) with history of colorectal adenoma within the past 3 years, age ≥ 35 years and ≤ 80 years. All patients received an upward titration of metformin over 3 weeks to 1000mg po bid, which was continued until the end-of-study (EOS) at 12 weeks. Rectal mucosa biopsies were obtained at baseline (BL) and at time of EOS endoscopy. Tissue S6Ser235 immunostaining was analyzed in a blinded fashion by the study pathologist using Histo Score (HScore) analysis. A paired t-test was used to examine the effect of metformin on activated S6serine235 (i.e., the ratio of pS6serine235/ S6serine235). Results: 45 patients were consented to achieve 32 eligible subjects. 4 subjects were removed from study due to Adverse Events (1 SAE, unrelated). In order of frequency, the most common AEs were diarrhea, cramping, flatulence, nausea, stomach pain; 80% of participants had Grade 1 AE, 27% had grade 2 AE. Mean (SD) weight and body mass index at BL were 105.2 (17.42) kg and 34.9 (5.57) respectively. Weight did not significantly differ over the course of the study. Glucose levels at EOS did not significantly differ from BL. Vitamin B12 levels were significantly reduced at EOS vs. BL (-46.7 pg/mL, 95% CI -73.2 to -20.2). Comparing EOS to BL tissue S6Ser235 by IHC HScore analysis, no significant differences were observed. Mean (SD) Hscore at BL was 1.1 (0.57) and 1.1 (0.51) at EOS. Median HScore change was 0.032 (p=0.77). Conclusions: Among obese CRA patients, 12 weeks of oral metformin 1000mg twice daily does not reduce pS6 levels in the rectal mucosa. Other potential mechanisms of action have not yet been analyzed. Data from this clinical trial indicate that metformin can be used safely in a non-diabetic population. Further research is needed to determine what effects, if any, metformin has on the target tissue of origin (colorectum) relevant to colorectal carcinogenesis if metformin is to be pursued as a CRC chemopreventive agent. Citation Format: Jason A. Zell, Christine E. McLaren, Timothy R. Morgan, Michael J. Lawson, Sherif Rezk, Gregory C. Albers, Wen-Pin Chen, Joseph C. Carmichael, Luz Rodriguez, Eva Szabo, Leslie Ford, Michael Pollak, Frank L. Meyskens. A Phase IIa trial of metformin for colorectal cancer risk reduction among patients with a history of colorectal adenomas and elevated body mass index. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A21.

Calcium/magnesium intake ratio, but not magnesium intake, interacts with genetic polymorphism in relation to colorectal neoplasia in a two-phase study.

Some studies suggest that the calcium to magnesium ratio intakes modify the associations of calcium or magnesium with risk of colorectal adenoma, adenoma recurrence, and cancer. Parathyroid hormone (PTH) plays a key role in the regulation of homeostasis for both calcium and magnesium. We hypothesized that polymorphisms in PTH and 13 other genes may modify the association between the calcium/magnesium intake ratio and colorectal neoplasia risk. We conducted a two-phase study including 1336 cases and 2891 controls from the Tennessee Colorectal Polyp Study. In Phase I, we identified 19 SNPs that significantly interacted with the calcium/magnesium intake ratio in adenoma risk. In Phase II, rs11022858 in PTH was replicated. In combined analysis of phases I and II, we found high calcium/magnesium intake ratio tended to be associated with a reduced risk of colorectal adenoma (P for trend, 0.040) among those who carried the TT genotype in rs11022858. In stratified analyses, calcium intake (≥ 1000 mg/d) was significantly associated with 64% reduced adenoma risk (OR = 0.36 (95% CI : 0.18-0.74)) among those homozygous for the minor allele (TT genotype) (P for trend, 0.012), but not associated with risk in other genotypes (CC/TC). Conversely, we found that highest magnesium intake was significantly associated with 27% reduced risk (OR = 0.73 (95% CI : 0.54-0.97)) of colorectal adenoma (P for trend, 0.026) among those who possessed the CC/TC genotypes, particularly among those with the TC genotype, whereas magnesium intake was not linked to risk among those with the TT genotype. These findings, if confirmed, will help for the development of personalized prevention strategies for colorectal cancer. © 2015 Wiley Periodicals, Inc.

Association of aspirin and NSAID use with risk of colorectal cancer according to genetic variants.

Use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with lower risk of colorectal cancer. To identify common genetic markers that may confer differential benefit from aspirin or NSAID chemoprevention, we tested gene × environment interactions between regular use of aspirin and/or NSAIDs and single-nucleotide polymorphisms (SNPs) in relation to risk of colorectal cancer. Case-control study using data from 5 case-control and 5 cohort studies initiated between 1976 and 2003 across the United States, Canada, Australia, and Germany and including colorectal cancer cases (n=8634) and matched controls (n=8553) ascertained between 1976 and 2011. Participants were all of European descent. Genome-wide SNP data and information on regular use of aspirin and/or NSAIDs and other risk factors. Colorectal cancer. Regular use of aspirin and/or NSAIDs was associated with lower risk of colorectal cancer (prevalence, 28% vs 38%; odds ratio [OR], 0.69 [95% CI, 0.64-0.74]; P = 6.2 × 10(-28)) compared with nonregular use. In the conventional logistic regression analysis, the SNP rs2965667 at chromosome 12p12.3 near the MGST1 gene showed a genome-wide significant interaction with aspirin and/or NSAID use (P = 4.6 × 10(-9) for interaction). Aspirin and/or NSAID use was associated with a lower risk of colorectal cancer among individuals with rs2965667-TT genotype (prevalence, 28% vs 38%; OR, 0.66 [95% CI, 0.61-0.70]; P = 7.7 × 10(-33)) but with a higher risk among those with rare (4%) TA or AA genotypes (prevalence, 35% vs 29%; OR, 1.89 [95% CI, 1.27-2.81]; P = .002). In case-only interaction analysis, the SNP rs16973225 at chromosome 15q25.2 near the IL16 gene showed a genome-wide significant interaction with use of aspirin and/or NSAIDs (P = 8.2 × 10(-9) for interaction). Regular use was associated with a lower risk of colorectal cancer among individuals with rs16973225-AA genotype (prevalence, 28% vs 38%; OR, 0.66 [95% CI, 0.62-0.71]; P = 1.9 × 10(-30)) but was not associated with risk of colorectal cancer among those with less common (9%) AC or CC genotypes (prevalence, 36% vs 39%; OR, 0.97 [95% CI, 0.78-1.20]; P = .76). In this genome-wide investigation of gene × environment interactions, use of aspirin and/or NSAIDs was associated with lower risk of colorectal cancer, and this association differed according to genetic variation at 2 SNPs at chromosomes 12 and 15. Validation of these findings in additional populations may facilitate targeted colorectal cancer prevention strategies.

Calcium Intake and Ion Transporter Genetic Polymorphisms Interact in Human Colorectal Neoplasia Risk in a 2-Phase Study

Background:The kidney-specific sodium-potassium-chloride cotransporter (NKCC2) protein encoded by solute carrier family 12 member 1 (SLC12A1) is the direct downstream effector of the inward-rectifier potassium channel (ROMK) encoded by potassium inwardly-rectifying channel, subfamily J, member 1 (KCNJ1), both of which are critical for calcium reabsorption in the kidney. Objective:We hypothesized that polymorphisms in KCNJ1, SLC12A1, and 7 other genes may modify the association between calcium intake and colorectal neoplasia risk. Methods:We conducted a 2-phase study in 1336 cases and 2891 controls from the Tennessee Colorectal Polyp Study. Results:In phase I, we identified 5 single-nucleotide polymorphisms (SNPs) that significantly interacted with calcium intake in adenoma risk. In phase II, rs2855798 in KCNJ1 was replicated. In combined analysis of phases I and II, the P values for interactions between calcium intake and rs2855798 were 1 × 10−4 for all adenoma and 5 × 10−3 for multiple/advanced adenoma. The highest calcium intake was not associated with risk among those with no variant allele but was significantly associated with a 41% reduced adenoma risk among those who carried at least 1 variant allele in KCNJ1. The corresponding reduction in risk of multiple or advanced adenomas was 52% among those with at least 1 variant allele. The P values for interactions between calcium intake and combined SNPs from the KCNJ1 and SLC12A1 genes were 7.5 × 10−5 for adenoma and 9.9 × 10−5 for multiple/advanced adenoma. The highest calcium intake was not associated with risk among those with nonvariant alleles in 2 genes but was significantly associated with a 34% reduced adenoma risk among those who carried a variant allele in 1 of the genes. The corresponding reduction in risk of multiple or advanced adenomas was 64% among those with variant alleles in both genes. Conclusion:These findings, if confirmed, will be critical for the development of personalized prevention strategies for colorectal cancer.

Fatty Acid Synthase in the Endoscopically Normal Rectal Mucosa as Marker for Obesity-related Colorectal Cancer (CRC) Risk: Gender-specific Implications: Presidential Poster

Purpose: The clinical implications of the profound biological differences in CRC between women and men are largely underappreciated. Our group has noted a “gender paradox” for advanced adenomas and CRC in women and men which may have potential ramifications for screening (JAMA 2009;302:1696-7). We have noted that changes in field carcinogenesis (reviewed in Gastroenterology 2011;140:35-41) may also be gender specific (Cancer Prev Res 2010;3:844-51). With regards to risk factor, the role of obesity is becoming increasingly dominant. Emerging data indicates that men appear to be disproportionately impacted versus women (reviewed by Bardou, et al. Gut 2013;62:933-47). Understanding which obese patients are at elevated risk of CRC is critical. We, therefore, evaluated fatty acid synthase (FASN), a protein implicated in the “lipogenic switch” in early colon carcinogenesis. FASN has been implicated in frank CRCs but little is known about the role of FASN in early events such as field carcinogenesis or its gender predilection. Methods: Two biopsies were obtained from endoscopically normal rectum from 103 patients undergoing screening colonoscopy. Subjects were dichotomized into non-obese and obese using a BMI of 30 as a cut point. Biopsies were subjected to real time PCR analysis for FASN and normalized with beta-actin. Results: Obese patients had an induction of FASN when compared to corresponding non-obese subjects (controls 50%, adenoma-harboring 29%, p<0.05). Rectal FASN was highly overexpressed in adenoma patients versus controls and this was a much more dramatic effect in men than women (see Figure). ANCOVA analysis suggested no significant confounding with age, adenoma size, smoking status, etc.FigureConclusion: We report herein, for the first time, alterations in FASN in patients harboring adenomas. This was accentuated in obese patients suggesting a potential molecular link between obesity and colonic neoplasia. Importantly, the effect was more marked in males than females, consonant with the obesity-CRC epidemiology. These insights into the molecular pathogenesis of obesity-related CRC suggest a role of this “lipogenic switch” in gender differences in CRC. Furthermore, this may be a “druggable” target against obesity-induced CRC and also provide a biomarker for determining at risk patients, thus enabling personalizing CRC prevention strategies.

Diabetes and Sex-specific Colorectal Cancer Risks in Newfoundland and Labrador: A Population-based Retrospective Cohort Study

Studies on the relationship between diabetes and colorectal cancer (CRC) are inconsistent. It is also unclear whether CRC risk elevation for individuals with diabetes is similar for males and females. Using data from Newfoundland and Labrador (NL), the province with the highest CRC incidence and diabetes prevalence in Canada, we assessed and compared the risk elevation of CRC for males and females with diabetes, overall and by anatomic subsite.A population-based retrospective cohort study including a study sample of 122,228 individuals aged ≥30 years was conducted using administrative health databases over a 10.5-year period (October 1, 1996 to March 31, 2007). Hazard ratios were estimated using Cox proportional hazard models.In comparison with non-diabetes counterparts, both males and females with diabetes were at a significantly elevated risk of overall CRC, with corresponding hazard ratios of 1.38 and 1.52, respectively. For males, diabetes significantly increased the risk of proximal and distal colon cancers, but not of rectal cancer. For females, diabetes significantly increased the risk of proximal colon and rectal cancers, but not of distal colon cancer. The results suggest that there is a stronger association between diabetes and CRC for females than for males, and the association did not change after adjusting for overweight/obesity.Diabetes led to a greater risk of CRC in both the male and female population in NL. Risk was subsite-specific and varied by sex. Future research should examine reasons for the observed diabetes-associated CRC risk to support CRC prevention strategies among the diabetes population.

Diabetes and sex-specific colorectal cancer risks in Newfoundland and Labrador: a population-based retrospective cohort study.

Studies on the relationship between diabetes and colorectal cancer (CRC) are inconsistent. It is also unclear whether CRC risk elevation for individuals with diabetes is similar for males and females. Using data from Newfoundland and Labrador (NL), the province with the highest CRC incidence and diabetes prevalence in Canada, we assessed and compared the risk elevation of CRC for males and females with diabetes, overall and by anatomic subsite. A population-based retrospective cohort study including a study sample of 122,228 individuals aged ≥30 years was conducted using administrative health databases over a 10.5-year period (October 1, 1996 to March 31, 2007). Hazard ratios were estimated using Cox proportional hazard models. In comparison with non-diabetes counterparts, both males and females with diabetes were at a significantly elevated risk of overall CRC, with corresponding hazard ratios of 1.38 and 1.52, respectively. For males, diabetes significantly increased the risk of proximal and distal colon cancers, but not of rectal cancer. For females, diabetes significantly increased the risk of proximal colon and rectal cancers, but not of distal colon cancer. The results suggest that there is a stronger association between diabetes and CRC for females than for males, and the association did not change after adjusting for overweight/obesity. Diabetes led to a greater risk of CRC in both the male and female population in NL. Risk was subsite-specific and varied by sex. Future research should examine reasons for the observed diabetes-associated CRC risk to support CRC prevention strategies among the diabetes population.

Multimodal Imaging of Growth and Rapamycin-Induced Regression of Colonic Adenomas in Apc Mutation-Dependent Mouse

We demonstrate that rapamycin can induce regression of adenomatous polyposis coli (Apc) mutation-dependent colonic adenomas in genetically engineered mice (CPC;Apc). An endoscope was used to visualize adenomas in CPC;Apc mice weekly for 10 weeks. The lesion surface areas were measured using a distance gauge and digitally generated grid. Coronal scans were performed on magnetic resonance imaging (MRI) to localize adenomas, and tumor volumes were measured from regions of interest drawn on consecutive axial scans. Rapamycin (5 mg/kg) was administered intraperitoneally daily for 5 weeks. Endoscopy and MRI were performed weekly to monitor adenoma regression. Caliper measurements and immunohistochemistry (IHC) were performed on adenomas postmortem. Dimensions from n = 30 adenomas in n = 7 animals were measured. Adenoma surface areas on endoscopy correlated with volumes on MRI and with postmortem caliper measurements, R(2) = 0.84 and R(2) = 0.81, respectively. The mean adenoma doubling times on endoscopy and MRI were 0.95 ± 0.14 and 1.21 ± 0.16 weeks, respectively. The minimum detectable adenoma surface area and volume on endoscopy and MRI was 0.69 mm(2) and 1.76 mm(3), respectively. On histology, the rapamycin-treated adenomas showed limited regions of dysplasia. Rapamycin therapy resulted in much lower mammalian target of rapamycin signaling and cell proliferation. Lower expression of phospho-S6 and reduced numbers of Ki67-positive cells were seen on IHC compared to vehicle-treated lesions. Endoscopy can be validated by MRI as a robust methodology for quantitative monitoring of therapy, representing a promising approach for future preclinical efforts to assess utility of novel colorectal cancer prevention strategies.

Abstract 1813: Implementation and outcomes of a community-based educational program in colorectal cancer prevention

Abstract Background: Cancer is the second most common cause of death in Puerto Rico (PR) after heart disease. Colorectal cancer (CRC) is the second most commonly diagnosed cancer among both men and women. The cancer screening guidelines given by the American Cancer Society indicate that adults should begin CRC screening at the age of 50. Although self-reported CRC screening from 1997 to 2006 have showed an increase in PR, CRC screening trends are lower than in the United States. With low screening rates and high CRC mortality in PR, health promotion programs aimed at education and prevention are needed. Methods: The purpose of this study was to evaluate a community-based educational program (Train-the-Trainer – TTTP) to increase knowledge and awareness of prevention about CRC in PR. The TTTP consisted of a formal didactic and hands-on seminar where participants were given didactic information and were trained to become trainers in CRC prevention. The TTTP was open to any adult, who was willing to become a trainer and committed to present the information in another forum using the materials provided at the TTTP. For the evaluation of this project, three main components were measured: (1) the Train the Trainers’ sessions; (2) the Participants’ Community Educational Sessions; and (3) the participant's experience delivering the training intervention. A total of five different questionnaires were design for the evaluation process of each component. Both qualitative and quantitative methods were used to collect data. Evaluations of outcomes were measured within 60-days of the TTT session. Results: Pre- and post-tests were given to the participants of the Train-the-Trainer session (N=115). There was a significant difference in the scores for the pre-test (mean=10.56, SD=2.57) and the post-test (mean=11.43, SD=1.83); t(96)=−4.68, p&amp;lt; 0.001); suggesting an augmentation in knowledge. Overall the participants from the community educational sessions (N=680) evaluated the program to be a success indicating that it provided them with knowledge, resources, and motivation to be screened for colorectal cancer, with 69.9% indicating their willingness to obtain a colonoscopy in the future. The trainer-to-trainee ratio was 1:6, with each participant of the TTTP training an average of 6 individuals from their own community within a 60-day period. Conclusion: The Puerto Rico CRC TTTP was effective in capacitating individuals to become trainers in their respective communities. The TTTP was effective in increasing knowledge of CRC prevention strategies and successfully reached members of the community. Implementation of a community-based program designed to develop trainers in CRC prevention demonstrated to be feasible and effective. Community based training programs are an alternative to promote CRC education and awareness in PR and may impact CRC screening rates, with subsequent decreases in mortality. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1813. doi:10.1158/1538-7445.AM2011-1813

Diagnosing Hereditary Colorectal Cancer

Although progress in the treatment of patients with colorectal cancer (CRC) has resulted in improved median survival, most patients with metastatic CRC still die of their disease, and essentially all patients with early-stage disease must undergo surgical resection and subsequently face the possibility of adjuvant chemotherapy. As effective screening and prevention strategies for CRC have been developed, identification of individuals with a hereditary predisposition to developing CRC is especially important and provides the opportunity to reduce disease burden in this high-risk population. Increased awareness and improved diagnostic techniques for hereditary CRC syndromes have facilitated more frequent diagnosis and management of a small number of highly penetrant syndromes within families. However, known high-penetrance genetic predisposition syndromes account for a minority of all familial CRC, leaving much of the genetic basis of CRC unexplained. Recent advances in high-throughput genotyping have made possible genome-wide association studies, which have identified novel genetic variants associated with modest increases in CRC risk. While these associations have helped to identify potentially important pathways in CRC carcinogenesis, at the current time, the clinical use of such genetic risk variants in colon cancer risk stratification remains limited.

10-Year risk of colorectal cancer: Development and validation of a prediction model in middle-aged Japanese men

Background: To estimate an individual's probability of developing colorectal cancer (CRC) may aid health professionals and individuals in improving lifestyle behaviors or deciding the screening regimens. As fewer studies on cancer risk prediction were seen so far, we initially developed an assessment tool with synthesizing key information from a variety of CRC risk factors through a large population-based cohort study. Method: The prediction model was derived from 28,115 men in the Japan Public Health Center-based (JPHC) Prospective Study Cohort II (follow-up: 1993–2005), with risk factors selected by Cox proportion hazard regression. 18,256 men in the JPHC Study Cohort I (follow-up: 1995–2005) were used to evaluate the model's performance. Results: 543 and 398 CRCs were diagnosed during the follow-up period in Cohorts II and I, respectively. The prediction model, including age, BMI, alcohol consumption, smoking status, and the daily physical activity level, showed modest discrimination ability for CRC ( C = 0.70; 95% confidential interval, 0.68–0.72) in Cohort II and well calibrated in Cohort I (Hosmer–Lemeshow χ 2 = 14.2, P = 0.08). Conclusion: The 10-year CRC risk prediction model may be used to estimate CRC risk in Japanese men. It may also play a role in the promotion of CRC prevention strategies.

Role of CT colonography in screening programs

Colorectal cancer kills 210,000 persons every year in Europe, its average incidence is 50 in 100,000 people/year, and the average lifetime risk of developing colorectal cancer is 5%. Treatment of colorectal cancer imposes a huge economical burden. The individual direct cost for treating colon cancer early is approximately €20,000. One course of chemotherapy using new combination regimens costs approximately €23,000, and caring for one patient with late-stage colorectal cancer costs approximately €80,000. Prevention of colorectal cancer is possible, and widespread implementation of CT colonography can reduce colorectal cancer incidence and mortality by up to 90%. Advances in technology have provided us with CT colonography, an effective test for imaging the colon, that may represent a formidable prevention tool, and be well accepted owing to its minimal invasiveness. This article gives an outline of the epidemiology and the available prevention strategies for colorectal cancer, illustrates the progress in CT colonography development, and discusses future perspectives.

Prevention and Screening of Gastrointestinal Cancers

This article reviews the current recommendations and data supporting various screening and prevention strategies for colorectal cancer (CRC) in average and high-risk individuals. Published research reports, epidemiologic data, and published guidelines from professional organizations. Properly applied screening tools can potentially decrease the morbidity and mortality associated with CRC. Nurses need to be aware of current recommendations for the early detection of CRC so they can provide patients with an accurate assessment of risk for developing CRC and education about the appropriate CRC screening guidelines.

Prevalence and Characteristics of Nonpolypoid Colorectal Neoplasm in an Asymptomatic and Average-Risk Chinese Population

Evidence from Japanese studies suggests that nonpolypoid colorectal neoplasia (NP-CRN) tends to be more pathologically advanced than polypoid neoplasia. However, data are limited regarding the prevalence of NP-CRN in an average-risk population. In addition, the diagnostic yield of the fecal occult blood test (FOBT) in relation to different types of colorectal neoplasms remains unclear. We prospectively investigated the prevalence and characteristics of polypoid and nonpolypoid colorectal lesions in an asymptomatic and average-risk Chinese population. The study included 12,731 asymptomatic Chinese subjects (8372 of whom were average-risk subjects) who underwent screening colonoscopy. The prevalence, histopathologic findings, and topographic distribution of polypoid and nonpolypoid colorectal lesions were determined and analyzed. The diagnostic yield of FOBT, in relation to lesion morphology, also was assessed. NP-CRN was detected in 552 (4.3%) asymptomatic and 348 (4.2%) average-risk subjects. The prevalence of depressed NP-CRN was 0.18% in both asymptomatic and average-risk subjects. A higher proportion of smaller-sized but high-grade dysplasia and invasive carcinoma beyond the submucosal layer was noted for depressed NP-CRN compared with flat NP-CRN or polypoid neoplasia. The diagnostic yield of FOBT was comparable in depressed lesions and their polypoid counterparts. The prevalence of NP-CRN is substantial in both asymptomatic and average-risk Chinese individuals. Some subcategories of NP-CRN in this population tend to have more advanced pathologic characteristics. These findings may lead to modification of screening and prevention strategies for colorectal cancer.

Gene-Gene, Gene-Environment & Multiple Interactions in Colorectal Cancer

This review comprehensively evaluates the influence of gene-gene, gene-environment and multiple interactions on the risk of colorectal cancer (CRC). Methods of studying these interactions and their limitations have been discussed herein. There is a need to develop biomarkers of exposure and of risk that are sensitive, specific, present in the pathway of the disease, and that have been clinically tested for routine use. The influence of inherited variation (polymorphism) in several genes has been discussed in this review; however, due to study limitations and confounders, it is difficult to conclude which ones are associated with the highest risk (either individually or in combination with environmental factors) to CRC. The majority of the sporadic cancer is believed to be due to modification of mutation risk by other genetic and/or environmental factors. Micronutrient deficiency may explain the association between low consumption of fruit/vegetables and CRC in human studies. Mitochondrial modulation by dietary factors influences the balance between cell renewal and death critical in colon mucosal homeostasis. Both genetic and epigenetic interactions are intricately dependent on each other, and collectively influence the process of colorectal tumorigenesis. The genetic and environmental interactions present a good prospect and a challenge for prevention strategies for CRC because they support the view that this highly prevalent cancer is preventable.

Increased Use of Colorectal Cancer Tests

Increased Use of Colorectal Cancer Tests

Risk of colon cancer in hereditary non-polyposis colorectal cancer patients as predicted by fuzzy modeling: Influence of smoking

To investigate whether a fuzzy logic model could predict colorectal cancer (CRC) risk engendered by smoking in hereditary non-polyposis colorectal cancer (HNPCC) patients. Three hundred and forty HNPCC mismatch repair (MMR) mutation carriers from the Creighton University Hereditary Cancer Institute Registry were selected for modeling. Age-dependent curves were generated to elucidate the joint effects between gene mutation (hMLH1 or hMSH2), gender, and smoking status on the probability of developing CRC. Smoking significantly increased CRC risk in male hMSH2 mutation carriers (P < 0.05). hMLH1 mutations augmented CRC risk relative to hMSH2 mutation carriers for males (P < 0.05). Males had a significantly higher risk of CRC than females for hMLH1 non smokers (P < 0.05), hMLH1 smokers (P < 0.1) and hMSH2 smokers (P < 0.1). Smoking promoted CRC in a dose-dependent manner in hMSH2 in males (P < 0.05). Females with hMSH2 mutations and both sexes with the hMLH1 groups only demonstrated a smoking effect after an extensive smoking history (P < 0.05). CRC promotion by smoking in HNPCC patients is dependent on gene mutation, gender and age. These data demonstrate that fuzzy modeling may enable formulation of clinical risk scores, thereby allowing individualization of CRC prevention strategies.

Will a 5-ASA a Day Keep the Cancer (and Dysplasia) Away?

Prevention strategies for colorectal cancer in chronic ulcerative colitis (UC) are currently based on the identification of neoplasia by surveillance colonoscopy, but there is a great interest in the possibility of primary chemoprevention. 5-aminosalicylic acid (5-ASA) therapy is an attractive option for chemoprevention in UC due to the fact that it is a derivative of aspirin and has been shown to have a variety of other molecular and genetic targets of cancer prevention, but human studies in UC have been limited by observational design and limited data collection or follow-up. The recently performed metaanalysis of 5-ASA chemoprevention trials shows a favorable role of 5-ASA in the prevention of cancer and dysplasia in patients with UC, and adds to the available evidence favoring its use. This editorial discusses the substantial logistical and ethical challenges in designing a randomized double-blind trial to measure the effect of 5-ASA on cancer risk in UC. The authors conclude that the safety and current maintenance use of 5-ASA warrant its acceptance as a probable chemopreventive agent at this time.