Colorectal cancer (CRC) is an illness strongly influenced by sex and gender, with mortality rates in males significantly higher than females. There is still a dearth of understanding on where sex ...differences exist along the pathway from presentation to survival. The aim of this review is to identify where actions are needed to improve outcomes for both sexes, and to narrow the gap for CRC.
A cross-sectional review of national data was undertaken to identify sex differences in incidence, screening uptake, route to diagnosis, cancer stage at diagnosis and survival, and their influence in the sex differences in mortality.
Overall incidence is higher in men, with an earlier age distribution, however, important sex differences exist in anatomical site. There were relatively small differences in screening uptake, route to diagnosis, cancer staging at diagnosis and survival. Screening uptake is higher in women under 69 years. Women are more likely to present as emergency cases, with more men diagnosed through screening and two-week-wait. No sex differences are seen in diagnosis for more advanced disease. Overall, age-standardised 5-year survival is similar between the sexes.
As there are minimal sex differences in the data from routes to diagnosis to survival, the higher mortality of colorectal cancer in men appears to be a result of exogenous and/or endogenous factors pre-diagnosis that lead to higher incidence rates. There are however, sex and gender differences that suggest more targeted interventions may facilitate prevention and earlier diagnosis in both men and women.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The importance of asymmetric divisions for stem cell function and maintenance is well established in the developing nervous system and the skin; however, its role in gut epithelium and its importance ...for tumorigenesis is still debated. We demonstrate alignment of mitotic spindles perpendicular to the apical surface specifically in the stem cell compartments of mouse and human intestine and colon. This orientation correlates with the asymmetric retention of label-retaining DNA. Both the preference for perpendicular spindle alignment and asymmetric label retention are lost in precancerous tissue heterozygous for the adenomatous polyposis coli tumor suppressor (
Apc). This loss correlates with cell shape changes specifically in the stem cell compartment. Our data suggest that loss of asymmetric division in stem cells might contribute to the oncogenic effect of
Apc mutations in gut epithelium.
► Mitotic spindles in intestinal stem cells align perpendicularly ► In precancerous tissue, this spindle orientation bias is lost ► Spindle alignment correlates with segregation of unreplicated DNA ► Loss of unreplicated DNA occurs more quickly in precancerous tissue
We present new, mass-independent, Ni isotope data for a range of bulk chondritic meteorites. The data are reported as epsilonsup 60Nisub 58/61, epsilonsup 62Nisub 58/61, and epsilonsup 64Nisub 58/61, ...or the parts per ten thousand deviations from a terrestrial reference, the NIST SRM 986 standard, of the sup 58Ni/sup 61Ni internally normalized sup 60Ni/sup 61Ni, sup 62Ni/sup 61Ni, and sup 64Ni/sup 61Ni ratios. We also determined to high precision the mass-dependent fractionation of two meteorite samples which span the range of epsilonsup 62Nisub 58/61 and epsilonsup 64Nisub 58/61. We have examined different nucleosynthetic environments to determine the possible source of the anomalous material responsible for the isotopic variations observed in Ni and other transition elements within bulk samples. Correlations of Ni isotope anomalies with O, Cr, and Ti isotope ratios and Pb/Yb in bulk meteorites suggest that the heterogeneous distribution of isotopic anomalies in the early solar system likely resulted from nebular sorting of chemically or physically different materials bearing different amounts of isotopes synthesized proximally to the collapse of the protosolar nebula.
In primary care, assessing which patients with bowel symptoms harbour significant disease (cancer, higher-risk adenoma or IBD) is difficult. We studied the diagnostic accuracies of faecal haemoglobin ...(FHb) and faecal calprotectin (FC) in a cohort of symptomatic patients.
From October 2013 to March 2014, general practitioners were prompted to request FHb and FC when referring patients with bowel symptoms to secondary care. Faecal samples were analysed for haemoglobin (EIKEN OC-Sensor io) and calprotectin (BÜHLMANN Calprotectin ELISA). Patients triaged to endoscopy were investigated within 6 weeks. All clinicians and endoscopists were blind to the faecal test results. The diagnostic accuracies of FHb and FC for identification of significant bowel disease were assessed.
1043 patients returned samples. FHb was detectable in 57.6% (median 0.4 µg/g, 95% CI 0.4 to 0.8; range 0-200). FC at 50 µg/g or above was present in 60.0%. 755 patients (54.6% women, median age 64 years (range 16-90, IQR 52-73)) returned samples and completed colonic investigations. 103 patients had significant bowel disease; the negative predictive values of FHb for colorectal cancer, higher-risk adenoma and IBD were 100%, 97.8% and 98.4%, respectively. Using cut-offs of detectable FHb and/or 200 µg/g FC detected two further cases of IBD, one higher-risk adenoma and no additional cancers.
In primary care, undetectable FHb is a good 'rule-out' test for significant bowel disease and could guide who requires investigation.
Currently, women are disadvantaged compared to men in colorectal cancer (CRC) screening, particularly in programmes that use faecal immunochemical tests for haemoglobin (FIT) followed by colonoscopy. ...Although there is no single cause for all the known disadvantages, many can be attributed to the ubiquitous finding that women have lower faecal haemoglobin concentrations (f-Hb) than men; there are many plausible reasons for this. Generally, a single f-Hb threshold is used in CRC screening programmes, leading to lower positivity for women than men, which causes poorer outcomes for women, including lower CRC detection rate, higher interval cancer (IC) proportion, and higher CRC mortality. Many of the now widely advocated risk scoring strategies do include factors taking account of sex, but these have not been extensively piloted or introduced. Using different f-Hb thresholds for the sexes seems advantageous, but there are difficulties, including deciding which characteristic should be selected to achieve equivalency, for example, positivity, IC proportions, or specificity. Moreover, additional colonoscopy resources, often constrained, would be required. Governments and their agencies should be encouraged to prioritise the allocation of resources to put simple strategies into practice, such as different f-Hb thresholds to create equal positivity in both sexes.
Colorectal cancer (CRC) screening reduces all-cause and CRC-related mortality. New research demonstrates that the faecal haemoglobin concentration (f-Hb) may indicate the presence of other serious ...diseases not related to CRC. We investigated the association between f-Hb, measured by a faecal immunochemical test (FIT), and both all-cause mortality and cause of death in a population-wide cohort of screening participants.
Between 2014 and 2018, 1,262,165 participants submitted a FIT for the Danish CRC screening programme. We followed these participants, using the Danish CRC Screening Database and several other national registers on health and population, until December 31, 2018. We stratified participants by f-Hb and compared them using a Cox proportional hazards regression on all-cause mortality and cause of death reported as adjusted hazard ratios (aHRs). We adjusted for several covariates, including comorbidity, socioeconomic factors, demography and prescription medication.
We observed 21,847 deaths in the study period. Our multivariate analyses indicated an association relationship between increasing f-Hb and the risk of dying in the study period. This risk increased steadily from aHR 1.38 (95% CI: 1.32, 1.44) in those with a f-Hb of 7.1-11.9 μg Hb/g faeces to 2.20 (95% CI: 2.10, 2.30) in those with a f-Hb ≥60.0 μg Hb/g faeces, when compared to those with a f-Hb ≤7.0 μg Hb/g faeces. The pattern remained when excluding CRC from the analysis. Similar patterns were observed between incrementally increasing f-Hb and the risk of dying from respiratory disease, cardiovascular disease and cancers other than CRC. Furthermore, we observed an increased risk of dying from CRC with increasing f-Hb.
Our findings support the hypothesis that f-Hb may indicate an elevated risk of having chronic conditions if causes for the bleeding have not been identified. The mechanisms still need to be established, but f-Hb may be a potential biomarker for several non-CRC diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We investigated demographic and clinical predictors of lower participation in bowel screening relative to breast and cervical screening.
Data linkage study of routinely collected clinical data from ...430,591 women registered with general practices in the Greater Glasgow & Clyde Health Board. Participation in the screening programmes was measured by attendance at breast or cervical screening or the return of a bowel screening kit.
72.6% of 159,993 women invited attended breast screening, 80.7% of 309,899 women invited attended cervical screening and 61.7% of 180,408 women invited completed bowel screening. Of the 68,324 women invited to participate in all three screening programmes during the study period, 52.1% participated in all three while 7.2% participated in none. Women who participated in breast (OR = 3.34 (3.21, 3.47), p < 0.001) or cervical (OR = 3.48 (3.32, 3.65), p < 0.001) were more likely to participate in bowel screening.
Participation in bowel screening was lower than breast or cervical for this population although the same demographic factors were associated with uptake, namely lower social deprivation, increasing age, low levels of comorbidity and prior non-malignant neoplasms. As women who complete breast and cervical are more likely to also complete bowel screening, interventions at these procedures to encourage bowel screening participation should be explored.
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