A risk-stratified approach to colorectal cancer prevention and diagnosis.
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ABSTRACT:
SUBMITTER: Hull MA
PROVIDER: S-EPMC7562765 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
Publications
A risk-stratified approach to colorectal cancer prevention and diagnosis.
Hull Mark A MA Rees Colin J CJ Sharp Linda L Koo Sara S
Nature reviews. Gastroenterology & hepatology 20201016 12
Population screening and endoscopic surveillance are used widely to prevent the development of and death from colorectal cancer (CRC). However, CRC remains a major cause of cancer mortality and the increasing burden of endoscopic investigations threatens to overwhelm some health services. This Perspective describes the rationale for and approach to improved risk stratification and decision-making for CRC prevention and diagnosis. Limitations of current approaches will be discussed using the UK a ...[more]
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Project description:BackgroundAlthough uniform colonoscopy screening reduces colorectal cancer (CRC) mortality, risk-based screening may be more efficient. We investigated whether CRC screening based on polygenic risk is a cost-effective alternative to current uniform screening, and if not, under what conditions it would be.MethodsThe MISCAN-Colon model was used to simulate a hypothetical cohort of US 40-year-olds. Uniform screening was modeled as colonoscopy screening at ages 50, 60, and 70 years. For risk-stratified screening, individuals underwent polygenic testing with current and potential future discriminatory performance (area under the receiver-operating curve [AUC] of 0.60 and 0.65-0.80, respectively). Polygenic testing results were used to create risk groups, for which colonoscopy screening was optimized by varying the start age (40-60 years), end age (70-85 years), and interval (1-20 years).ResultsWith current discriminatory performance, optimal screening ranged from once-only colonoscopy at age 60 years for the lowest-risk group to six colonoscopies at ages 40-80 years for the highest-risk group. While maintaining the same health benefits, risk-stratified screening increased costs by $59 per person. Risk-stratified screening could become cost-effective if the AUC value would increase beyond 0.65, the price per polygenic test would drop to less than $141, or risk-stratified screening would lead to a 5% increase in screening participation.ConclusionsCurrently, CRC screening based on polygenic risk is unlikely to be cost-effective compared with uniform screening. This is expected to change with a greater than 0.05 increase in AUC value, a greater than 30% reduction in polygenic testing costs, or a greater than 5% increase in adherence with screening.
| S-EPMC6988584 | biostudies-literature
Project description:BackgroundColorectal cancer defined as cancer of the colon or rectum, is the third most frequently diagnosed cancer in men and the second in women, and, according to the World Health Organization database GLOBOCAN, it accounts for nearly 1.4 million new cases annually worldwide. The occurrence of colorectal cancer is associated with nonmodifiable risk factors, including age and hereditary factors, as well as with modifiable environmental and lifestyle factors.MethodsThe study included 800 patients, 400 diagnosed with colorectal cancer and 400 within the control group, who gave their written informed consent to participate in the study. Patients with cancer other than colorectal cancer were randomly selected for control group I, and patients with no cancer diagnosis were selected for control group II. The method used was a case-control study - an observational and analytical study with a control group, conducted among patients of the Clinical Oncology Centre and the Provincial Hospital in the years 2019-2020. The study comparing the exposure was carried out in a group of people who developed the endpoint, that is colorectal cancer, with the exposure in a well-matched group of controls who did not reach the endpoint. Assessment of activity and BMI was used according to WHO recommendations, as well as the expert system. The data were tested for the distribution and the homogeneity of variance was validated before applying the parameter tests. Comparison of quantitative variables between groups was performed using ANOVA.ResultsThe mean age of the patients was 64.53 ± 8.86 years, of the control group I - 59.64 ± 9.33 and the control group II - 57.5 (7.83). There was a strong positive association between the incidence of ulcerative colitis and the risk of colorectal cancer (P < .01). Among obese subjects, the risk of developing colorectal cancer was 1.27 (95% CI, 1.06-1.53) compared with nonobese subjects. A strong positive relationship was found between low physical activity converted to metabolic equivalent of MET effort per week and the risk of colorectal cancer (P < .001). The relative risk for current smokers was 2.17 (95% CI 1.79-2.66). There was an association between higher fat consumption and higher red meat consumption and the risk of developing colorectal cancer (P < .01).ConclusionsObesity, low physical activity, active and passive smoking and high salt and red meat consumption have been associated with an increased risk of colorectal cancer. These findings provide further evidence of the importance of maintaining a healthy lifestyle.
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Project description:Knowledge of genetics and its implications for human health is rapidly evolving in accordance with recent events, such as discoveries of large numbers of disease susceptibility loci from genome-wide association studies, the US Supreme Court ruling of the non-patentability of human genes, and the development of a regulatory framework for commercial genetic tests. In anticipation of the increasing relevance of genetic testing for the assessment of disease risks, this Review provides a summary of the methodologies used for building, evaluating and applying risk prediction models that include information from genetic testing and environmental risk factors. Potential applications of models for primary and secondary disease prevention are illustrated through several case studies, and future challenges and opportunities are discussed.
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| S-EPMC2634716 | biostudies-other
Project description:IntroductionIncreased knowledge of breast cancer risk factors may enable a paradigm shift from one-size-fits-all breast cancer screening to screening and subsequent prevention guided by a woman's individual risk of breast cancer. Professionals will play a key role in informing women about this new personalised screening and prevention programme. Therefore, it is essential to explore professionals' views of the acceptability of this new programme, since this may affect shared decision-making.MethodsProfessionals from three European countries (the Netherlands, United Kingdom, and Sweden) participated in digital concept mapping, a systematic mixed methods approach used to explore complex multidimensional constructs.ResultsAcross the three countries, professionals prioritised the following five themes which may impact decision-making from the perspective of eligible women: (1) Anxiety/worry; (2) Proactive approach; (3) Reassurance; (4) Lack of knowledge; and (5) Organisation of risk assessment and feedback. Furthermore, Dutch and British professionals expressed concerns regarding the acceptability of a heterogeneous screening policy, suggesting women will question their risk feedback and assigned pathway of care. Swedish professionals emphasised the potential impact of the programme on family relations.ConclusionsThe perspectives of Dutch, British, and Swedish professionals of women's decision-making regarding personalised breast cancer screening and prevention generally appear in line with women's own views of acceptability as previously reported. This will facilitate shared decision-making. However, concerns regarding potential consequences of this new programme for screening outcomes and organisation need to be addressed, since this may affect how professionals communicate the programme to eligible women.
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Project description:Untargeted metabolomic studies have identified potential biomarkers of colorectal cancer risk, but evidence is still limited and broadly inconsistent. Among 39,239 Cancer Prevention Study II Nutrition cohort participants who provided a blood sample between 1998-2001, 517 newly diagnosed colorectal cancers were identified through 30 June 2015. In this nested case-control study, controls were matched 1:1 to cases on age, sex, race and date of blood draw. Mass spectroscopy-based metabolomic analyses of pre-diagnostic plasma identified 886 named metabolites, after quality control exclusions. Conditional logistic regression models estimated multivariable-adjusted odds ratios (OR) and 95% confidence intervals (CI) for 1 standard deviation (SD) increase in each metabolite with risk of colorectal cancer. Six metabolites were associated with colorectal cancer risk at a false discovery rate < 0.20. These metabolites were of several classes, including cofactors and vitamins, nucleotides, xenobiotics, lipids and amino acids. Five metabolites (guanidinoacetate, 2'-O-methylcytidine, vanillylmandelate, bilirubin (E,E) and N-palmitoylglycine) were positively associated (OR per 1 SD = 1.29 to 1.32), and one (3-methylxanthine) was inversely associated with CRC risk (OR = 0.79, 95% CI, 0.69-0.89). We did not replicate findings from two earlier prospective studies of 250 cases each after adjusting for multiple comparisons. Large pooled prospective analyses are warranted to confirm or refute these findings and to discover and replicate metabolites associated with colorectal cancer risk.
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