Objectives: The European Code Against Cancer recommends individuals aged ≥50 should participate in colorectal cancer screening. CT-colonography (CTC) is one of several screening tests available. We systematically reviewed evidence on, and identified key factors influencing, cost-effectiveness of CTC screening.

Methods: PubMed, Medline, and the Cochrane library were searched for cost-effectiveness or cost-utility analyses of CTC-based screening, published in English, January 1999 to July 2010. Data was abstracted on setting, model type and horizon, screening scenario(s), comparator(s), participants, uptake, CTC performance and cost, effectiveness, ICERs, and whether extra-colonic findings and medical complications were considered.

Results: Sixteen studies were identified from the United States (n = 11), Canada (n = 2), and France, Italy, and the United Kingdom (1 each). Markov state-transition (n = 14) or microsimulation (n = 2) models were used. Eleven considered direct medical costs only; five included indirect costs. Fourteen compared CTC with no screening; fourteen compared CTC with colonoscopy-based screening; fewer compared CTC with sigmoidoscopy (8) or fecal tests (4). Outcomes assessed were life-years gained/saved (13), QALYs (2), or both (1). Three considered extra-colonic findings; seven considered complications. CTC appeared cost-effective versus no screening and, in general, flexible sigmoidoscopy and fecal occult blood testing. Results were mixed comparing CTC to colonoscopy. Parameters most influencing cost-effectiveness included: CTC costs, screening uptake, threshold for polyp referral, and extra-colonic findings.

Conclusion: Evidence on cost-effectiveness of CTC screening is heterogeneous, due largely to between-study differences in comparators and parameter values. Future studies should: compare CTC with currently favored tests, especially fecal immunochemical tests; consider extra-colonic findings; and conduct comprehensive sensitivity analyses.

Diets rich in flavonoids may reduce the risk of developing colorectal cancer. Flavonoids are widely distributed in foods of plant origin, though in the UK tea is the main dietary source. Our objective was to evaluate any independent associations of total dietary and non-tea intake of four flavonoid subclasses and the risk of developing colorectal cancer in a tea-drinking population with a high colorectal cancer incidence. A population-based case–control study (264 cases with histologically confirmed incident colorectal cancer and 408 controls) was carried out. Dietary data gathered by FFQ were used to calculate flavonoid intake. Adjusted OR and 95 % CI were estimated by logistic regression. No linear association between risk of developing colorectal cancer and total dietary flavonol, procyanidin, flavon-3-ol or flavanone intakes was found, but non-tea flavonol intake was inversely associated with colorectal cancer risk (OR 0·6; 95 % CI 0·4, 1·0). Stratification by site of cancer and assessment of individual flavonols showed a reduced risk of developing colon but not rectal cancer with increasing non-tea quercetin intake (OR 0·5; 95 % CI 0·3, 0·8; Ptrend < 0·01). We concluded that flavonols, specifically quercetin, obtained from non-tea components of the diet may be linked with reduced risk of developing colon cancer.

Folate is key in one-carbon metabolism, disruption of which can interfere with DNA synthesis, repair, and methylation. Efficient one-carbon metabolism requires other B vitamins and the optimal activity of enzymes including 5,10-methylenetetrahydrofolate reductase (MTHFR). We report a population-based case–control study of folate intake, related dietary factors and MTHFR polymorphisms (C677T, A1298C) and colorectal cancer in a population with relatively high colorectal cancer incidence and relatively low folate intake. A total of 264 cases with histologically confirmed incident colorectal cancer and 408 controls participated. There was no clear trend in risk with reported intakes of total, or dietary, folate, riboflavin, vitamin B12 or vitamin B6, nor were there interactions between folate intake and the other B vitamins or alcohol. For C677T, risk decreased with increasing variant alleles (multivariate OR for CT v. CC = 0·77 (95 % CI 0·52, 1·16); OR for TT v. CC = 0·62 (95 % CI 0·31, 1·24)), which, although not statistically significant, was consistent with previous studies. For A1298C, compared with AA subjects, CC subjects had modest, non-significant, reduced risk (multivariate OR = 0·81 (95 % CI 0·45, 1·49)). There were significant interactions between total folate and C677T (P = 0·029) and A1298C (P = 0·025), and total vitamin B6 and both polymorphisms (C677T, P = 0·016; A1298C, P = 0·033), although the patterns observed differed from previous studies. Seen against the setting of low folate intake, the results suggest that the role of folate metabolism in colorectal cancer aetiology may be more complex than previously thought. Investigation of particular folate vitamers (for example, tetrahydrofolate, 5,10-methylenetetrahydrofolate) may help clarify carcinogenesis pathways.

Objectives: The aim of this study was to estimate the time and travel costs generated by women when attending for Papanicolaou (Pap) smear tests or colposcopy appointments in the United Kingdom, both absolutely and relative to the health service cost of the national cervical cancer screening programs.

Methods: Data were obtained from questionnaires completed by two samples of women participating in a three-center trial of management of low-grade abnormalities detected by screening (n = 1,106 for Pap smears and n = 1,203 for colposcopy appointments). Women were 20 to 59 years of age and resident in Grampian or Tayside, Scotland, or Nottingham, England. Questionnaire data were supplemented with sociodemographic information previously collected at the time of recruitment to the trial.

Results: The mean total time and travel costs per attendance at a smear test and at a colposcopy appointment were estimated to be £9.2 and £27.4, respectively, averaged across the three trial areas (valued at 2002 prices). Statistically significant intercenter disparities in time and travel costs were identified, particularly with respect to colposcopy appointments. For these, time and travel costs in Nottingham were substantially less than those in Grampian and Tayside (£22.9, £30.2, and £32.1, respectively). Time and travel costs amount to 26 and 33 percent, approximately, over and above the direct health service costs of the English and Scottish screening programs, respectively.

Conclusions: The time and travel costs associated with participation in the UK cervical cancer screening programs are substantial and are not spatially uniform across the country.

Lower levels of dietary folate are associated with the development of epithelial cell tumours in man, particularly colo-rectal cancer. In the majority of epidemiological studies blood folate or reported folate intake have been shown to be inversely related to colo-rectal cancer risk. Folate, via its pivotal role in C1 metabolism, is crucial both for DNA synthesis and repair, and for DNA methylation. This function is compromised when vitamin B12 is low. Vitamin B12 deficiency has been shown to increase biomarkers of DNA damage in man but there is no evidence directly linkinglow vitamin B12 with cancer. Disturbingly, folate and vitamin B12 deficiencies are common in the general population, particularly in the underprivileged and the elderly. How folate and/or vitamin B12 deficiency influence carcinogenesis remains to be established, but it is currently believed that they may act to decrease DNA methylation, resulting in proto-oncogene activation, and/or to induce instabilityin the DNA molecule via a futile cycle of uracil misincorporation and removal. The relative importance of these two pathways may become clear by determining both DNA stability and cytosine methylation in individuals with different polymorphic variants of key folate-metabolising enzymes. 5,10-Methylenetetrahydrofolate reductase converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate and thereby controls whether folate is employed for DNA synthesis or DNA methylation. Colo-rectal cancer risk is decreased in subjects homozygous for a common variant (C677T) of the gene coding for this enzyme, suggesting that DNA synthesis and repair may be ‘enhanced’ in these individuals. Evidence from animal and human studies is presented here in support of folate acting to maintain genomic stability through both these mechanisms.

This paper reports 3-dimensional confocal microscopy observations on how nephrogenic aggregates form from the NCAM- and Pax2-positive caps (4–5 cells deep) of condensed metanephric mesenchyme surrounding the duct tips of the mouse kidney. Aggregates of 6–8 cells are first seen at ∼E12.5–12.75 immediately proximal to this cap, closely abutting the duct surface. As the tip advances, NCAM expression is maintained in the cap but is otherwise restricted to aggregates whose cells rapidly epithelialise, forming tubules that invade the duct epithelium. Pax2 expression studies shows how the rind of nephrogenic blastemal cells forms: as duct tips extend towards the kidney surface, the associated Pax2+ cells form patches of cells on the kidney surface. These observations revise our knowledge of the timing and process of nephron initiation.