Search

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.eeh.2010.05.003 Byline: Timothy J. Hatton (a), Richard M. Martin (b) Keywords: Fertility decline; Heights of children; Health in Britain Abstract: In this paper we argue that the fertility decline that began around 1880 had substantial positive effects on the health of children, as the quality-quantity trade-off would suggest. We use microdata from a unique survey from 1930s Britain to analyse the relationship at the household level between the standardised heights of children and the number of children in the family. Our results suggest that heights are influenced positively by family income per capita and negatively by the number of children or the degree of crowding in the household. The evidence suggests that family size affected the health of children through its influence on both nutrition and disease. Applying our results to long-term trends, we find that rising household income and falling family size contributed significantly to improving child health between 1886 and 1938. Between 1906 and 1938 these variables account for 40% of the increase in heights, and much of this effect is due to falling family size. We conclude that the fertility decline is a neglected source of the rapid improvement in health in the first half of the twentieth century. Author Affiliation: (a) Australian National University, Australia, and University of Essex, United Kingdom (b) University of Bristol, United Kingdom Article History: Received 28 April 2009

Background The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited. Objectives To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR). Methods Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions. Results Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk. Conclusions These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer. [ABSTRACT FROM AUTHOR]

Background: Previous observational studies have consistently shown slower weight and length gains in infants with prolonged breastfeeding than in those who were formula-fed from birth or breastfed for a shorter duration. These studies inferred that prolonged breastfeeding causes slower growth in infancy. Objective: We compared infant growth associated with ≥12 mo of breastfeeding with a shorter duration of breastfeeding on the basis of 3 different analytic approaches to the same data from a randomized trial: intention-to-treat (ITT; "as randomized"), observational ("as fed"), and instrumental variable (IV; by using randomization as an "instrument" to achieve ≥12 mo of breastfeeding). Design: This was a cluster-randomized trial of a breastfeeding-promotion intervention. Anthropometric measurements were obtained at birth and at 1, 2, 3, 6, 9, and 12 mo. Results: The 3 analytic approaches yielded different results. The ITT approach showed more rapid growth in the first 2 mo among infants randomly assigned to the breastfeeding-promotion intervention than among control infants, with a decreasing difference over the ensuing months and nearly identical weight, length, and body mass index by 12 mo. The observational analysis showed a different trend: higher weight and length in infants who were breastfed ≥12 mo than in those who were breastfed <12 mo during the first 3 mo and no difference by 6 mo, while infants who were breastfed <12 mo showed increasingly higher weight and length from 6 to 12 mo. The IV analysis showed a temporal pattern that was similar to that seen in the ITT analysis, but with larger (and less precise) differences between infants breastfed for ≥12 compared with <12 mo. Conclusions: We observed major differences in experimental (ITT and IV) compared with observational approaches to analyzing data obtained from the same children. These approaches lead to opposite causal inferences about the relation between infant feeding and growth and underline the importance of ensuring that the postulated cause (feeding) temporally precedes its hypothesized effect (growth). [ABSTRACT FROM AUTHOR]

To examine associations between the transcription factors CCCTC-binding factor (CTCF) and forkhead box protein A1 (FOXA1) and the androgen receptor (AR) and their association with components of the insulin-like growth factor (IGF)-pathway in a cohort of men with localized prostate cancer. Using prostate tissue samples collected during the Prostate cancer: Evidence of Exercise and Nutrition Trial (PrEvENT) trial (N = 70 to 92, depending on section availability), we assessed the abundance of CTCF, FOXA1, AR, IGFIR, p-mTOR, PTEN and IGFBP-2 proteins using a modified version of the Allred scoring system. Validation studies were performed using large, publicly available datasets (TCGA) (N = 489). We identified a strong correlation between CTCF and AR staining with benign prostate tissue. CTCF also strongly associated with the IGF IR, with PTEN and with phospho-mTOR. FOXA1 was also correlated with staining for the IGF-IR, with IGFBP-2 and with staining for activated phosphor-mTOR. The staining for the IGF-IR was strongly correlated with the AR. Our findings emphasise the close and complex links between the endocrine controls, well known to play an important role in prostate cancer, and the transcription factors implicated by the recent genetic evidence. • What is already known on this topic: CCCTC-binding factor, forkhead box protein A1 and the insulin-like growth factor axis are important in prostate cancer. • What this study adds: Novel links between endocrine controls, the IGF-axis and key transcription factors, such as FOXA1 and the AR. • How this study might affect research, practice, or policy: Optimising treatment strategies by identifyingrelevant molecular associations found in tissue from men with prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Clinically diagnosed eating disorders may have adverse cardiometabolic consequences, including overweight or obesity and high blood pressure. However, the link between problematic eating attitudes in early adolescence, which can lead to disordered eating behaviors, and future cardiometabolic health is, to our knowledge, unknown. Objective: We assessed whether variations in midchildhood eating attitudes influence the future development of overweight or obesity and high blood pressure. Design: Of 17,046 children who participated in the Promotion of Breastfeeding Intervention Trial (PROBIT), we included 13,557 participants (79.5% response rate) who completed the Children's Eating Attitudes Test (ChEAT) at age 11.5 y and in whom we measured adiposity and blood pressure at ages 6.5, 11.5, and 16 y. We assessed whether ChEAT scores ≥85th percentile (indicative of problematic eating attitudes) compared with scores ≥85th percentile at age 11.5 y were associated with new-onset overweight, obesity, high systolic blood pressure, or high diastolic blood pressure between midchildhood and early adolescence. Results: After controlling for baseline sociodemographic confounders, we observed positive associations of problematic eating attitudes at age 11.5 y with new-onset obesity (OR: 2.18; 95% CI: 1.58, 3.02), newonset high systolic blood pressure (OR: 1.34; 95% CI: 1.05, 1.70), and new-onset high diastolic blood pressure (OR: 1.25; 95% CI: 0.99, 1.58) at age 16 y. After further controlling for body mass index at age 6.5 y, problematic eating attitudes remained positively associated with newonset obesity (OR: 1.80; 95% CI: 1.28, 2.53); however, associations with new-onset high blood pressure were attenuated (OR: 1.14; 95% CI: 0.89, 1.45 and OR: 1.09; 95% CI: 0.86, 1.39 for new-onset systolic and diastolic blood pressure, respectively). Conclusions: Problematic eating attitudes in midchildhood seem to be related to the development of obesity in adolescence, a relatively novel observation with potentially important public health implications for obesity control. [ABSTRACT FROM AUTHOR]

Background: Several recent "developmental origins" studies have reported increased long-term risks of adiposity, especially truncal adiposity, among children born small for gestational age (SGA). Objective: We assessed the effects of SGA birth and weight gain in early infancy on adiposity at age 11.5 y. Design: From a cluster-randomized breastfeeding promotion trial in 17,046 Belarusian children, we measured height, weight, waist and hip circumferences, triceps and subscapular skinfold thicknesses, and bioimpedance measures of percentage body fat at age 11.5 y. Children born SGA (birth weight <10th percentile) and those born large for gestational age (LGA; >90th percentile for gestational age) were compared with those born appropriate for gestational age (AGA). Weight gain from birth to 6 mo was categorized as high (>0.67-SD increase in weight-for-age), low (>0.67-SD decrease in weight-forage), or normal. Multilevel statistical models accounted for clustered measurement and controlled for maternal and paternal height and body mass index (BMI), maternal education, geographic region, urban compared with rural residence, and the child's exact age at follow-up. Results: Children born SGA had a significantly lower BMI, percentage body fat, and fat mass index than did those born AGA, with a dose-response effect across 2 subcategories of SGA (P<0.001 for all comparisons). No difference was observed in waist-to-hip ratio, although the subscapular-to-triceps skinfold ratio was slightly but significantly (P<0.001) higher in children born SGA. Differences among the study groups continued to increase since the previous follow-up at 6.5 y. SGA infants with catch-up growth in the first 3-6 mo had growth and adiposity measures intermediate between those born SGA without catch-up and those born AGA. Opposite effects of similar magnitude were observed in children born LGA. Conclusion: The 11.5-y-old Belarusian children born SGA were shorter, were thinner, and had less body fat than their non-SGA peers, irrespective of postnatal weight gain. [ABSTRACT FROM AUTHOR]

Background: Differences between mothers who do and do not succeed in breastfeeding are likely to confound associations of lactation with later maternal adiposity. Objective: We compared adiposity and blood pressure (BP) in women randomly assigned to an intervention to promote prolonged and exclusive breastfeeding or usual care. Design: We performed a cluster-randomized trial at 31 hospitals in Belarus in 19961997. Results: Of 17,046 women enrolled at delivery, we assessed 11,867 women (69.6%) at 11.5 y postpartum. The prevalence of exclusive breastfeeding ±3 mo was 44.5% in 6321 women in the intervention group and 7.1% in 5546 women in the control group. At 11.5 y postpartum, mean (6SD) body mass index (BMI; in kg/m²) was 26.5 ± 5.5, the percentage of body fat was 33.6% ± 8.3%, and systolic BP was 124.6 ± 14.6 mm Hg. On intention-to-treat analysis (without imputation) with adjustment for clustering by hospital, mean outcomes were lower in intervention compared with control mothers for BMI (mean difference: -0.27; 95% CI: -0.91, 0.37), body fat (-0.49%; 95% CI: -1.25%, 0.27%), and systolic BP (-0.81 mm Hg; 95% CI: -3.33, 1.71 mm Hg), but effect sizes were small, CIs were wide, and results were attenuated further toward the null after adjustment for baseline characteristics. Results were similar in sensitivity analyses [ie, by using conventional observational analyses disregarding treatment assignment, instrumental variable analyses to estimate the causal effect of breastfeeding, and multiple imputation to account for missing outcome measures (n = 17,046)]. Conclusion: In women who initiated breastfeeding, an intervention to promote longer breastfeeding duration did not result in an important lowering of adiposity or BP. This trial was registered at clinicaltrials.gov as NCT01561612 and at Current Controlled Trials as ISRCTN37687716. [ABSTRACT FROM AUTHOR]

Background: Weight and length at birth (which represent fetal growth) and weight and length or height gain during childhood (which potentially represent catch-up growth) may be related to later health outcomes. However, methods for the assessment of such relations are complex and underdeveloped. Objectives: We aimed to describe childhood weight and length or height trajectories and to relate these to later outcomes by using rash at age 6.5 y as an example. Design: The data came from a prospective cohort study in Belarus in 10,494 children born in 31 hospitals that participated in a cluster randomized trial of breastfeeding promotion. Weight and length or height were measured at birth, at scheduled clinic visits up to 1 y, and at 6.5 y; intermediate measures were obtained from routine child health records. Linear spline multilevel models for weight and length or height were used to estimate each child's deviance from average birth weight, birth length, weight, and length or height gain velocity in each time period. Logistic regression was used to relate the outcome (parental report of rash at 6.5 y) to these weight and length or height estimates. Results: The best-fitting splines for length or height and weight had knots at 3 and 12 mo, with another knot at 34 mo for height. The only relation between weight and length or height and reported rash was a positive association with weight gain velocity between 12 and 34 mo (odds ratio per SD increase in weight gain velocity: 1.11; 95% CI: 1.01, 1.22). Conclusion: Advantages of multilevel models include no restriction to measures at arbitrary times or to individuals with complete data and allowance for measurement error. [ABSTRACT FROM AUTHOR]

The evidence that breast-feeding protects against obesity is based on observational studies, with potential for confounding and selection bias. This article summarizes a previously published study in which we assessed whether an intervention designed to promote exclusive and prolonged breast-feeding affects children's height, weight, adiposity, and blood pressure (BP) at age 6.5 y. The Promotion of Breastfeeding Intervention Trial (PROBIT) a cluster-randomized trial of a breast-feeding promotion intervention based on the WHO/UNICEF Baby-Friendly Hospital Initiative. A total of 17,046 healthy breast-fed infants were enrolled from 31 Belarussian maternity hospitals and affiliated clinics, of whom 13,889 181.5%) were followed up at 6.5 y with duplicate measurements of height, weight, waist circumference, triceps and subscapular skinfold thicknesses, systolic and diastolic BP. Analysis was based on intention to treat, with statistical adjustment for clustering within hospitals/clinics to permit inferences at the individual level. The experimental intervention led to a large increase in exclusive breast-feeding at 3 mo (43.3% vs. 6.4%, P < 0.001) and a significantly higher prevalence of any breast-feeding throughout infancy. No significant intervention effects were observed on height, BMI, adiposity measures, or BP. The breast-feeding promotion intervention resulted in substantial increases in the duration and exclusivity of breast-feeding yet did not reduce measures of adiposity at age 6.5 y. Previous reports of protective effects against obesity may reflect uncontrolled bias caused by confounding and selection. [ABSTRACT FROM AUTHOR]

Summary: Background: There is no conclusive evidence that screening based on serum prostate-specific antigen (PSA) tests decreases prostate-cancer mortality. Since its introduction in the USA around 1990, uptake of PSA testing has been rapid in the USA, but much less common in the UK. Our aim was to study trends over time in prostate-cancer mortality and incidence in the USA and UK in 1975–2004, and compare these patterns with trends in screening and treatment. Methods: Joinpoint regression analysis of cancer-mortality statistics from Cancer Research UK (London, UK) and from the US National Cancer Institute Surveillance, Epidemiology and End Results (SEER) programme from 1975 to 2004 was used to estimate the annual percentage change in prostate-cancer mortality in both countries and the points in time when trends changed. The ratio of USA to UK age-adjusted prostate-cancer incidence was also assessed. Findings: Age-specific and age-adjusted prostate-cancer mortality peaked in the early 1990s at almost identical rates in both countries, but age-adjusted mortality in the USA subsequently declined after 1994 by −4·17% (95% CI −4·34 to −3·99) each year, four-times the rate of decline in the UK after 1992 (−1·14% [−1·44 to −0·84]). The mortality decline in the USA was greatest and most sustained in patients aged 75 years or older (−5·32% [−8·23 to −2·32]), whereas death rates had plateaued in this age group in the UK by 2000. The mean ratio of USA to UK age-adjusted prostate-cancer incidence rates in 1975–2003 was 2·5, with a pronounced peak around the time that PSA testing was introduced in the USA. Numbers needed to treat to prevent one death from prostate cancer were 33 000 in the 55–64-year age group. Interpretation: The striking decline in prostate-cancer mortality in the USA compared with the UK in 1994–2004 coincided with much higher uptake of PSA screening in the USA. Explanations for the different trends in mortality include the possibility of an early effect of initial screening rounds on men with more aggressive asymptomatic disease in the USA, different approaches to treatment in the two countries, and bias related to the misattribution of cause of death. Speculation over the role of screening will continue until evidence from randomised controlled trials is published. Funding: ProMPT (Prostate Cancer: Mechanisms of Progression and Treatment) collaborative (UK National Cancer Research Institute, London, UK, and UK Medical Research Council, London, UK). [Copyright &y& Elsevier]

Background: Observational evidence suggests that having been breastfed in infancy may reduce the prevalence of type 2 diabetes in later life. Objective: The objective was to examine the influence of initial breastfeeding on type 2 diabetes and blood glucose and insulin concentrations. Design: A systematic review of published studies identified 1010 reports; 23 examined the relation between infant feeding and type 2 diabetes in later life or risk factors for diabetes. Risk factors in infants were examined separately from those in children and adults. All estimates were pooled by using fixed-effect models; differences <0 and ratios < 1 imply a beneficial effect of breastfeeding. Results: Subjects who were breastfed had a lower risk of type 2 diabetes in later life than did those who were formula fed (7 studies; 76 744 subjects; odds ratio: 0.61; 95% CI: 0.44, 0.85; P = 0.003). Children and adults without diabetes who had been breastfed had marginally lower fasting insulin concentrations than did those who were formula fed (6 studies; 4800 subjects; percentage difference: -3%; 95% CI: -8%, 1%; P = 0.13); no significant difference in fasting glucose concentrations was observed. Breastfed infants had lower mean preprandial blood glucose (12 studies; 560 subjects; mean difference: -0.17 mmol/L; 95% CI: -0.28, -0.05 mmol/L; P = 0.005) and insulin (7 studies; 291 subjects; mean difference: - 2.86 pmol/L; 95% CI: -5.76, 0.04 pmol/L; P = 0.054) concentrations than did those who were formula fed. Conclusion: Breastfeeding in infancy is associated with a reduced risk of type 2 diabetes, with marginally lower insulin concentrations in later life, and with lower blood glucose and serum insulin concentrations in infancy. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether early life body mass index (BMI; in kg/m2) is associated with adult cardiovascular disease. Objective: The objective was to assess the association of early life BMI with the risk of ischemic heart disease (IHD) and stroke. Design: The association between early life BMI and risk of adult mortality from IHD and stroke was assessed in 3 historical cohort studies in which height and weight had been assessed by using standard procedures. Participants were traced and linked to national mortality data. Participants in the 3 cohorts were born between 1922 and 1937, 1927 and 1956, and 1928 and 1950 and were aged 2-15, 9-18, and 16-22 y, respectively, at the time of assessment of their height and weight. Results: Participants in all 3 cohorts had mean BMIs similar to those reported for contemporary children and young adults, but fewer of the cohort participants were overweight or obese. BMI was not associated with future risk ofIHDor stroke in any cohort. The pooled (all 3 cohorts) adjusted hazard ratio per SD of early lifeBMIwas 1.09 (95% CI: 1.01, 1.19) for IHD and 0.94 (95% CI: 0.82, 1.08) for stroke. The pooled hazard ratio of IHD when participants who were overweight or obese for their age were compared with all other participants was 1.34 (95% CI: 0.95, 1.91), and no association was found between overweight or obesity and stroke risk. The effects of BMI did not vary by cohort or by age. Conclusion: These results do not provide strong evidence that being overweight or obese in childhood is associated with future cardiovascular disease risk. [ABSTRACT FROM AUTHOR]

Background: Evidence from observational studies has suggested that breastfeeding may reduce the prevalence of obesity in later life. Objective: The objective was to examine whether initial breastfeeding is related to lower mean body mass index (BMI; in kg/m2) throughout life. Design: The study was a systematic review of published studies investigating the association between infant feeding and a measure of obesity or adiposity in later life, which was supplemented with data from unpublished sources. Analyses were based on the mean differences in BMI between those subjects who were initially breastfed and those who were formula-fed (expressed as breastfed minus bottle-fed), which were pooled by using fixed-effects models throughout. Results: From 70 eligible studies, 36 mean differences in BMI(from 355 301 subjects) between those breastfed and those formula-fed (reported as exclusive feeding in 20 studies) were obtained. Breastfeeding was associated with a slightly lower mean BMI than was formula feeding (-0.04; 95% CI: -0.05, -0.02). The mean difference in BMIs appeared larger in 15 small studies of⩾1000 subjects (-0.19; 95% CI: -0.31, -0.08) and smaller in larger studies of <1000 subjects (-0.03; 95% CI:-0.05,-0.02). An Egger test was statistically significant (P=0.002). Adjustment for socioeconomic status, maternal smoking in pregnancy, and maternal BMI in 11 studies abolished the effect (-0.10; 95% CI: -0.14, -0.06 before adjustment; -0.01; 95% CI: -0.05, 0.03 after adjustment). Conclusions: Mean BMI is lower among breastfed subjects. However, the difference is small and is likely to be strongly influenced by publication bias and confounding factors. Promotion of breastfeeding, although important for other reasons, is not likely to reduce mean BMI. [ABSTRACT FROM AUTHOR]

Background: Evidence suggests that environmental factors acting early in life may affect blood pressure in adulthood. Objective: The objective was to test the hypothesis that dried formula milk (derived from cow milk) intake in infancy is positively associated with blood pressure in early adulthood. Design: We conducted a long-term follow-up (1997-1999) of the Barry Caerphilly Growth study cohort (1972-1974) into which mothers and their offspring had originally been randomly assigned to receive a milk supplement or usual care. Participants were the offspring, who were aged 23-27 y at followup. The main outcome measures were systolic and diastolic blood pressure. Results: The social and demographic characteristics of the subjects who were (n = 679) and were not (n = 272) followed up were similar. For each increase in quartile of dried milk consumption (in oz) at 3 mo of age, there was a 1.28-mm Hg (95% CI: 0.46, 2.10 mm Hg) increase in systolic and a 0.63-mm Hg (95% CI: 0.04, 1.22 mm Hg) increase in diastolic blood pressure after adjustment for sex, intervention group, birth weight z scores, social class in childhood, age at follow-up, alcohol consumption, and pack-years of smoking. These coefficients were attenuated when adult body mass index and height were included in the models, but the association of dried milk consumption at 3 mo of age with systolic pressure remained significant (1.07 mm Hg; 95% CI: 0.27, 1.87 mm Hg). Conclusions: Our findings are consistent with the hypothesis that high blood pressure in later life is influenced by early postnatal nutrition. Thus, interventions to optimize infant nutrition may have important long-term health benefits. [ABSTRACT FROM AUTHOR]

The author discusses the article "General and abdominal fat outcomes in school-age children associated with infant breastfeeding patterns" by B. Durmu§ et al. which appeared within the issue. Topics mentioned include the value of birth cohort studies in life-course epidemiology, the association of socioeconomic status to child and adult obesity, and the inclusion of height in the expanded multivariable regression results of the study.

Human studies examining associations between circulating levels of insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) and colorectal cancer risk have reported inconsistent results. We conducted complementary serologic and Mendelian randomization (MR) analyses to determine whether alterations in circulating levels of IGF1 or IGFBP3 are associated with colorectal cancer development. Serum levels of IGF1 were measured in blood samples collected from 397,380 participants from the UK Biobank, from 2006 through 2010. Incident cancer cases and cancer cases recorded first in death certificates were identified through linkage to national cancer and death registries. Complete follow-up was available through March 31, 2016. For the MR analyses, we identified genetic variants associated with circulating levels of IGF1 and IGFBP3. The association of these genetic variants with colorectal cancer was examined with 2-sample MR methods using genome-wide association study consortia data (52,865 cases with colorectal cancer and 46,287 individuals without [controls]) After a median follow-up period of 7.1 years, 2665 cases of colorectal cancer were recorded. In a multivariable-adjusted model, circulating level of IGF1 associated with colorectal cancer risk (hazard ratio per 1 standard deviation increment of IGF1, 1.11; 95% confidence interval [CI] 1.05–1.17). Similar associations were found by sex, follow-up time, and tumor subsite. In the MR analyses, a 1 standard deviation increment in IGF1 level, predicted based on genetic factors, was associated with a higher risk of colorectal cancer risk (odds ratio 1.08; 95% CI 1.03–1.12; P = 3.3 × 10–4). Level of IGFBP3, predicted based on genetic factors, was associated with colorectal cancer risk (odds ratio per 1 standard deviation increment, 1.12; 95% CI 1.06–1.18; P = 4.2 × 10–5). Colorectal cancer risk was associated with only 1 variant in the IGFBP3 gene region (rs11977526), which also associated with anthropometric traits and circulating level of IGF2. In an analysis of blood samples from almost 400,000 participants in the UK Biobank, we found an association between circulating level of IGF1 and colorectal cancer. Using genetic data from 52,865 cases with colorectal cancer and 46,287 controls, a higher level of IGF1, determined by genetic factors, was associated with colorectal cancer. Further studies are needed to determine how this signaling pathway might contribute to colorectal carcinogenesis. [ABSTRACT FROM AUTHOR]

Context Many men with clinically localized prostate cancer are being monitored as part of active surveillance (AS) programs, but little is known about reasons for receiving radical treatment. Objectives A systematic review of the evidence about AS was undertaken, with a meta-analysis to identify predictors of radical treatment. Evidence acquisition A comprehensive search of the Embase, MEDLINE and Web of Knowledge databases to March 2014 was performed. Studies reporting on men with localized prostate cancer followed by AS or monitoring were included. AS was defined where objective eligibility criteria, management strategies, and triggers for clinical review or radical treatment were reported. Evidence synthesis The 26 AS cohorts included 7627 men, with a median follow-up of 3.5 yr (range of medians 1.5–7.5 yr). The cohorts had a wide range of inclusion criteria, monitoring protocols, and triggers for radical treatment. There were eight prostate cancer deaths and five cases of metastases in 24 981 person-years of follow-up. Each year, 8.8% of men (95% confidence interval 6.7–11.0%) received radical treatment, most commonly because of biopsy findings, prostate-specific antigen triggers, or patient choice driven by anxiety. Studies in which most men changed treatment were those including only low-risk Gleason score 6 disease and scheduled rebiopsies. Conclusions The wide variety of AS protocols and lack of robust evidence make firm conclusions difficult. Currently, patients and clinicians have to make judgments about the balance of risks and benefits in AS protocols. The publication of robust evidence from randomized trials and longer-term follow-up of cohorts is urgently required. Patient summary We reviewed 26 studies of men on active surveillance for prostate cancer. There was evidence that studies including men with the lowest risk disease and scheduled rebiopsy had higher rates of radical treatment. [ABSTRACT FROM AUTHOR]

Background: Studies have indicated that the presence and size of subclinical atherosclerotic plaques improve the prediction of atherosclerotic cardiovascular events (ASCVE) over and above that provided by conventional risk factors alone. However, the relative contribution of different ultrasonographic measurements and sites of measurements on the 10-year ASCVD risk is largely unknown.Objectives: Our aims were to determine the relative performance of carotid intima-media thickness, plaque thickness, and plaque area in 10-year ASCVD prediction when added to conventional risk factors as well as whether the vascular territory of these measurements, carotid or common femoral bifurcation, and the number of bifurcations with plaque (NBP) influence prediction.Methods: We enrolled 985 adults (mean age: 58.1 ± 10.2 years) free of atherosclerotic cardiovascular disease. Conventional risk factors were recorded, and both carotid and common femoral bifurcations were scanned with ultrasonography. The primary endpoint was a composite of first-time fatal or nonfatal ASCVE.Results: Over a mean ± SD follow-up of 13.2 ± 3.7 years, ASCVE occurred in 154 (15.6%) participants. By adding different plaque measurements to conventional risk factors in a Cox model, net reclassification improvement was 10.4% with maximum intima-media thickness, 9.5% with carotid plaque thickness, and 14.2% with carotid plaque area. It increased to 16.1%, 16.6%, and 16.6% (P < 0.0001) by adding measurements from 4 bifurcations: NBP, total plaque thickness, and total plaque area, respectively.Conclusions: NBP, total plaque thickness, or total plaque area from both the carotid and common femoral bifurcations provides a better prediction of future ASCVE than measurements from a single site. The results need to be validated in an independent cohort. [ABSTRACT FROM AUTHOR]

Objectives: Recent innovations in prostate cancer diagnosis include new biomarkers and more accurate biopsy methods. This study assesses the evidence base on cost-effectiveness of these developments (eg, Prostate Health Index and magnetic resonance imaging [MRI]-guided biopsy) and identifies areas of improvement for future cost-effectiveness models.Methods: A systematic review using the National Health Service Economic Evaluation Database, MEDLINE, Embase, Health Technology Assessment databases, National Institute for Health and Care Excellence guidelines, and United Kingdom National Screening Committee guidance was performed, between 2009 and 2021. Relevant data were extracted on study type, model inputs, modeling methods and cost-effectiveness conclusions, and results narratively synthesized.Results: A total of 22 model-based economic evaluations were included. A total of 11 compared the cost-effectiveness of new biomarkers to prostate-specific antigen testing alone and all found biomarkers to be cost saving. A total of 8 compared MRI-guided biopsy methods to transrectal ultrasound-guided methods and found MRI-guided methods to be most cost-effective. Newer detection methods showed a reduction in unnecessary biopsies and overtreatment. The most cost-effective follow-up strategy in men with a negative initial biopsy was uncertain. Many studies did not model for stage or grade of cancer, cancer progression, or the entire testing and treatment pathway. Few fully accounted for uncertainty.Conclusions: This review brings together the cost-effectiveness literature for novel diagnostic methods in prostate cancer, showing that most studies have found new methods to be more cost-effective than standard of care. Several limitations of the models were identified, however, limiting the reliability of the results. Areas for further development include accurately modeling the impact of early diagnostic tests on long-term outcomes of prostate cancer and fully accounting for uncertainty. [ABSTRACT FROM AUTHOR]

The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer (PCa) randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. To determine report outcomes according to treatment received in men in randomised and treatment choice cohorts. This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Two cohorts included 1643 men who agreed to be randomised; 997 declined randomisation and chose treatment. Health-related quality of life impacts on urinary, bowel, and sexual function were assessed using patient-reported outcome measures. Analysis was carried out based on treatment received for each cohort and on pooled estimates using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and outdating of the interventions being evaluated during the lengthy follow-up required in trials of screen-detected PCa. Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. More than 90 out of every 100 men with localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are much better after active monitoring, but the risks of spreading of prostate cancer are more common. Prostate cancer is very common, affecting about one in nine men during their lifetime, but most do not die or develop complications. The ProtecT trial randomised men with prostate-specific antigen-detected localised prostate cancer to active monitoring (AM), radical prostatectomy, or radiotherapy, and followed them up for 10 yr. We found that >90 out of every 100 men with localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring (AM), surgery, or radiotherapy. Side effects on sexual and bladder function are much better after AM than after radical treatments, but the risks of spreading of prostate cancer are greater after AM. [ABSTRACT FROM AUTHOR]