Publications
325 results found
Butt J, Jenab M, Werner J, et al., 2021, Association of pre-diagnostic antibody responses to escherichia coli and bacteroides fragilis toxin proteins with colorectal cancer in a European cohort, Gut Microbes, Vol: 13, Pages: 1-14, ISSN: 1949-0976
Experimental evidence has implicated genotoxic Escherichia coli (E. coli) and enterotoxigenic Bacteroides fragilis (ETBF) in the development of colorectal cancer (CRC). However, evidence from epidemiological studies is sparse. We therefore assessed the association of serological markers of E. coli and ETBF exposure with odds of developing CRC in the European Prospective Investigation into Nutrition and Cancer (EPIC) study.Serum samples of incident CRC cases and matched controls (n = 442 pairs) were analyzed for immunoglobulin (Ig) A and G antibody responses to seven E. coli proteins and two isoforms of the ETBF toxin via multiplex serology. Multivariable-adjusted conditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of sero-positivity to E. coli and ETBF with CRC.The IgA-positivity of any of the tested E. coli antigens was associated with higher odds of developing CRC (OR: 1.42; 95% CI: 1.05–1.91). Dual-positivity for both IgA and IgG to E. coli and ETBF was associated with >1.7-fold higher odds of developing CRC, with a significant association only for IgG (OR: 1.75; 95% CI: 1.04, 2.94). This association was more pronounced when restricted to the proximal colon cancers (OR: 2.62; 95% CI: 1.09, 6.29) compared to those of the distal colon (OR: 1.24; 95% CI: 0.51, 3.00) (pheterogeneity = 0.095). Sero-positivity to E. coli and ETBF was associated with CRC development, suggesting that co-infection of these bacterial species may contribute to colorectal carcinogenesis. These findings warrant further exploration in larger prospective studies and within different population groups.
Woodfield G, Belluomo I, Boshier PR, et al., 2021, Feasibility and acceptability of breath research in primary care: a prospective, cross-sectional, observational study, BMJ Open, Vol: 11, Pages: 1-10, ISSN: 2044-6055
Objectives To examine the feasibility and acceptability of breath research in primary care.Design Non-randomised, prospective, mixed-methods cross-sectional observational study.Setting Twenty-six urban primary care practices.Participants 1002 patients aged 18–90 years with gastrointestinal symptoms.Main outcome measures During the first 6 months of the study (phase 1), feasibility of patient enrolment using face-to-face, telephone or SMS-messaging (Short Message Service) enrolment strategies, as well as processes for breath testing at local primary care practices, were evaluated. A mixed-method iterative study design was adopted and outcomes evaluated using weekly Plan-Do-Study-Act cycles, focus groups and general practitioner (GP) questionnaires.During the second 6 months of the study (phase 2), patient and GP acceptability of the breath test and testing process was assessed using questionnaires. In addition a ‘single practice’ recruitment model was compared with a ‘hub and spoke’ centralised recruitment model with regards to enrolment ability and patient acceptability.Throughout the study feasibility of the collection of a large number of breath samples by clinical staff over multiple study sites was evaluated and quantified by the analysis of these samples using mass spectrometry.Results 1002 patients were recruited within 192 sampling days. Both ‘single practice’ and ‘hub and spoke’ recruitment models were effective with an average of 5.3 and 4.3 patients accrued per day, respectively. The ‘hub and spoke’ model with SMS messaging was the most efficient combined method of patient accrual. Acceptability of the test was high among both patients and GPs. The methodology for collection, handling and analysis of breath samples was effective, with 95% of samples meeting quality criteria.Conclusions Large-scale breath testing in primary care was feasible and acceptable. This study provides a practical fra
Christakoudi S, Pagoni P, Ferrari P, et al., 2021, Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, International Journal of Cancer, Vol: 148, Pages: 1637-1651, ISSN: 0020-7136
Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241,323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20,960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio HR=1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (+/-0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR=1.41; 1.01-1.96), post-menopausal breast (HR=1.08, 1.00-1.16) and thyroid (HR=1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organization categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the post-menopausal breast (HR=1.19; 1.06-1.33), ovary (HR=1.40; 1.04-1.91), corpus uteri (HR=1.42; 1.06-1.91), kidney (HR=1.80; 1.20-2.68) and pancreas in men (HR=1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR=0.40; 0.23-0.69) and colon (HR=0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood.
Pearson-Stuttard J, Bennett J, Vamos E, et al., 2021, Trends in predominant causes of death in individuals with and without diabetes in England from 2001 to 2018: an epidemiological analysis of linked primary care records, The Lancet Diabetes and Endocrinology, Vol: 9, Pages: 165-173, ISSN: 2213-8595
BackgroundThe prevalence of diabetes has increased in the UK and other high-income countries alongside a substantial decline in cardiovascular mortality. Yet data are scarce on how these trends have changed the causes of death in people with diabetes who have traditionally died primarily of vascular causes. We estimated how all-cause mortality and cause-specific mortality in people with diabetes have changed over time, how the composition of the mortality burden has changed, and how this composition compared with that of the non-diabetes population.MethodsIn this epidemiological analysis of primary care records, we identified 313 907 individuals with diabetes in the Clinical Practice Research Datalink, a well described primary care database, between 2001 to 2018, and linked these data to UK Office for National Statistics mortality data. We assembled serial cross sections with longitudinal follow-up to generate a mixed prevalence and incidence study population of patients with diabetes. We used discretised Poisson regression models to estimate annual death rates for deaths from all causes and 12 specific causes for men and women with diabetes. We also identified age-matched and sex matched (1:1) individuals without diabetes from the same dataset and estimated mortality rates in this group.FindingsBetween Jan 1, 2001, and Oct 31, 2018, total mortality declined by 32% in men and 31% in women with diagnosed diabetes. Death rates declined from 40·7 deaths per 1000 person-years to 27·8 deaths per 1000 person-years in men and from 42·7 deaths per 1000 person-years to 29·5 deaths per 1000 person-years in women with diagnosed diabetes. We found similar declines in individuals without diabetes, hence the gap in mortality between those with and without diabetes was maintained over the study period. Cause-specific death rates declined in ten of the 12 cause groups, with exceptions in dementia and liver disease, which increased in both populations. Th
Pearson-Stuttard J, Bennett J, Cheng Y, et al., 2021, Trends in predominant causes of death in those with and without diabetes in England from 2001 to 2018, The Lancet Diabetes and Endocrinology, Vol: 9, Pages: 165-173, ISSN: 2213-8595
BackgroundThe prevalence of diabetes has increased in the UK and other high-income countries alongside a substantial decline in cardiovascular mortality. Yet data are scarce on how these trends have changed the causes of death in people with diabetes who have traditionally died primarily of vascular causes. We estimated how all-cause mortality and cause-specific mortality in people with diabetes have changed over time, how the composition of the mortality burden has changed, and how this composition compared with that of the non-diabetes population.MethodsIn this epidemiological analysis of primary care records, we identified 313 907 individuals with diabetes in the Clinical Practice Research Datalink, a well described primary care database, between 2001 to 2018, and linked these data to UK Office for National Statistics mortality data. We assembled serial cross sections with longitudinal follow-up to generate a mixed prevalence and incidence study population of patients with diabetes. We used discretised Poisson regression models to estimate annual death rates for deaths from all causes and 12 specific causes for men and women with diabetes. We also identified age-matched and sex matched (1:1) individuals without diabetes from the same dataset and estimated mortality rates in this group.FindingsBetween Jan 1, 2001, and Oct 31, 2018, total mortality declined by 32% in men and 31% in women with diagnosed diabetes. Death rates declined from 40·7 deaths per 1000 person-years to 27·8 deaths per 1000 person-years in men and from 42·7 deaths per 1000 person-years to 29·5 deaths per 1000 person-years in women with diagnosed diabetes. We found similar declines in individuals without diabetes, hence the gap in mortality between those with and without diabetes was maintained over the study period. Cause-specific death rates declined in ten of the 12 cause groups, with exceptions in dementia and liver disease, which increased in both populations. Th
Brenner H, Cross AJ, 2021, Merits, challenges, and limitations of randomized trials on colorectal cancer screening effectiveness., Gastroenterology, Vol: 160, Pages: 1009-1011, ISSN: 0016-5085
Jayasekara H, MacInnis RJ, Lujan-Barroso L, et al., 2021, Lifetime alcohol intake, drinking patterns over time and risk of stomach cancer: A pooled analysis of data from two prospective cohort studies, International Journal of Cancer, Vol: 148, Pages: 2759-2773, ISSN: 0020-7136
Alcohol consumption is causally linked to several cancers but the evidence for stomach cancer is inconclusive. In our study, the association between long-term alcohol intake and risk of stomach cancer and its subtypes was evaluated. We performed a pooled analysis of data collected at baseline from 491 714 participants in the European Prospective Investigation into Cancer and Nutrition and the Melbourne Collaborative Cohort Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for incident stomach cancer in relation to lifetime alcohol intake and group-based life course intake trajectories, adjusted for potential confounders including Helicobacter pylori infection. In all, 1225 incident stomach cancers (78% noncardia) were diagnosed over 7 094 637 person-years; 984 in 382 957 study participants with lifetime alcohol intake data (5 455 507 person-years). Although lifetime alcohol intake was not associated with overall stomach cancer risk, we observed a weak positive association with noncardia cancer (HR = 1.03, 95% CI: 1.00-1.06 per 10 g/d increment), with a HR of 1.50 (95% CI: 1.08-2.09) for ≥60 g/d compared to 0.1 to 4.9 g/d. A weak inverse association with cardia cancer (HR = 0.93, 95% CI: 0.87-1.00) was also observed. HRs of 1.48 (95% CI: 1.10-1.99) for noncardia and 0.51 (95% CI: 0.26-1.03) for cardia cancer were observed for a life course trajectory characterized by heavy decreasing intake compared to light stable intake (Phomogeneity = .02). These associations did not differ appreciably by smoking or H pylori infection status. Limiting alcohol use during lifetime, particularly avoiding heavy use during early adulthood, might help prevent noncardia stomach cancer. Heterogeneous associations observed for cardia and noncardia cancers may indicate etiologic differences.
Aleksandrova K, Reichmann R, Kaaks R, et al., 2021, Development and validation of a lifestyle-based model for colorectal cancer risk prediction: the LiFeCRC score, BMC Medicine, Vol: 19, ISSN: 1741-7015
BACKGROUND: Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population. METHODS: The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992-2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed. RESULTS: The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell's C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, li
Robbins EC, Wooldrage K, Saunders BP, et al., 2021, P22 Impact of adenoma detection rates at flexible sigmoidoscopy on long-term colorectal cancer incidence and mortality, Abstracts of the BSG Campus, Publisher: BMJ PUBLISHING GROUP, Pages: A53-A53, ISSN: 0017-5749
Harewood R, Wooldrage K, Kinross J, et al., 2021, O56 Risk factors for proximal colon cancer: how informative are polyp findings in determining future risk?, BSG Virtual Campus, Publisher: BMJ Publishing Group, Pages: A31-A31, ISSN: 0017-5749
Bull CJ, Bell JA, Murphy N, et al., 2020, Adiposity, metabolites, and colorectal cancer risk: Mendelian randomization study, BMC Medicine, Vol: 18, ISSN: 1741-7015
BackgroundHigher adiposity increases the risk of colorectal cancer (CRC), but whether this relationship varies by anatomical sub-site or by sex is unclear. Further, the metabolic alterations mediating the effects of adiposity on CRC are not fully understood.MethodsWe examined sex- and site-specific associations of adiposity with CRC risk and whether adiposity-associated metabolites explain the associations of adiposity with CRC. Genetic variants from genome-wide association studies of body mass index (BMI) and waist-to-hip ratio (WHR, unadjusted for BMI; N = 806,810), and 123 metabolites from targeted nuclear magnetic resonance metabolomics (N = 24,925), were used as instruments. Sex-combined and sex-specific Mendelian randomization (MR) was conducted for BMI and WHR with CRC risk (58,221 cases and 67,694 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry). Sex-combined MR was conducted for BMI and WHR with metabolites, for metabolites with CRC, and for BMI and WHR with CRC adjusted for metabolite classes in multivariable models.ResultsIn sex-specific MR analyses, higher BMI (per 4.2 kg/m2) was associated with 1.23 (95% confidence interval (CI) = 1.08, 1.38) times higher CRC odds among men (inverse-variance-weighted (IVW) model); among women, higher BMI (per 5.2 kg/m2) was associated with 1.09 (95% CI = 0.97, 1.22) times higher CRC odds. WHR (per 0.07 higher) was more strongly associated with CRC risk among women (IVW OR = 1.25, 95% CI = 1.08, 1.43) than men (IVW OR = 1.05, 95% CI = 0.81, 1.36). BMI or WHR was associated with 104/123 metabolites at false discovery rate-corrected P ≤ 0.05; several metabolites were associated with CRC, but not in directions that were consistent with the mediation of positive adiposity-CRC relatio
Anderson AS, Renehan AG, Saxton JM, et al., 2020, Cancer prevention through weight control-where are we in 2020?, British Journal of Cancer, Vol: 124, Pages: 1049-1056, ISSN: 0007-0920
Growing data from epidemiological studies highlight the association between excess body fat and cancer incidence, but good indicative evidence demonstrates that intentional weight loss, as well as increasing physical activity, offers much promise as a cost-effective approach for reducing the cancer burden. However, clear gaps remain in our understanding of how changes in body fat or levels of physical activity are mechanistically linked to cancer, and the magnitude of their impact on cancer risk. It is important to investigate the causal link between programmes that successfully achieve short-term modest weight loss followed by weight-loss maintenance and cancer incidence. The longer-term impact of weight loss and duration of overweight and obesity on risk reduction also need to be fully considered in trial design. These gaps in knowledge need to be urgently addressed to expedite the development and implementation of future cancer-control strategies. Comprehensive approaches to trial design, Mendelian randomisation studies and data-linkage opportunities offer real possibilities to tackle current research gaps. In this paper, we set out the case for why non-pharmacological weight-management trials are urgently needed to support cancer-risk reduction and help control the growing global burden of cancer.
Anderson AS, Martin RM, Renehan AG, et al., 2020, Cancer survivorship, excess body fatness and weight-loss intervention-where are we in 2020?, British Journal of Cancer, Vol: 124, Pages: 1057-1065, ISSN: 0007-0920
Earlier diagnosis and more effective treatments mean that the estimated number of cancer survivors in the United Kingdom is expected to reach 4 million by 2030. However, there is an increasing realisation that excess body fatness (EBF) is likely to influence the quality of cancer survivorship and disease-free survival. For decades, the discussion of weight management in patients with cancer has been dominated by concerns about unintentional weight loss, low body weight and interventions to increase weight, often re-enforced by the existence of the obesity paradox, which indicates that high body weight is associated with survival benefits for some types of cancer. However, observational evidence provides strong grounds for testing the hypothesis that interventions for promoting intentional loss of body fat and maintaining skeletal muscle in overweight and obese cancer survivors would bring important health benefits in terms of survival outcomes and long-term impact on treatment-related side effects. In this paper, we outline the need for studies to improve our understanding of the health benefits of weight-loss interventions, such as hypocaloric healthy-eating plans combined with physical activity. In particular, complex intervention trials that are pragmatically designed are urgently needed to develop effective, clinically practical, evidence-based strategies for reducing EBF and optimising body composition in people living with and beyond common cancers.
Robbins E, Wooldrage K, Stenson I, et al., 2020, Heterogeneity in colorectal cancer incidence among people recommended three-yearly surveillance post-polypectomy: a validation study, Endoscopy, Vol: 53, Pages: 402-410, ISSN: 0013-726X
BackgroundColonoscopy surveillance is recommended for patients at increased risk of colorectal cancer (CRC) following adenoma removal. Low-, intermediate-, and high-risk groups are defined by baseline adenoma characteristics. We previously evaluated surveillance in intermediate-risk patients using UK hospital data, identifying a higher-risk subgroup who benefitted from surveillance and a lower-risk subgroup who may not require surveillance. Here we explored whether these findings apply in individuals undergoing CRC screening. MethodsRetrospective study using data from the UK Flexible Sigmoidoscopy Screening Trial (UKFSST), English CRC screening pilot (ECP), and US Kaiser Permanente CRC prevention programme (KPCP). Screening participants aged 50–74 years and classed as intermediate-risk at baseline colonoscopy were included. CRC data were available through 2006 (KPCP) or 2014 (UKFSST, ECP). We classified participants into lower- and higher-risk subgroups using our previously identified baseline risk factors; higher-risk participants were those with incomplete colonoscopies, poor bowel preparation, adenomas ≥20mm or with high-grade dysplasia, or proximal polyps. We compared CRC incidence rates in these subgroups and in the presence versus absence of surveillance using Cox regression.ResultsOf 2291 intermediate-risk participants, 45% were classified as higher-risk. Median follow-up was 11.8 years. CRC incidence rates were significantly higher in the higher-risk than lower-risk subgroup (hazard ratio [HR]=2.08, 95%CI 1.07–4.06). Surveillance reduced CRC incidence rates in higher-risk participants (HR=0.35, 0.14–0.86), but not statistically significantly so in lower-risk participants (HR=0.41, 0.12–1.38).ConclusionAs previously demonstrated for hospital patients, screening participants classed as intermediate-risk comprise two risk subgroups. Surveillance clearly benefits the higher-risk subgroup.
Aglago EK, Rinaldi S, Freisling H, et al., 2020, Soluble Receptor for Advanced Glycation End-products (sRAGE) and Colorectal Cancer Risk: A Case-Control Study Nested within a European Prospective Cohort, Cancer Epidemiology, Biomarkers and Prevention, Vol: 30, ISSN: 1055-9965
BACKGROUND: Overexpression of the receptor for advanced glycation end-product (RAGE) has been associated with chronic inflammation, which in turn has been associated with increased colorectal cancer risk. Soluble RAGE (sRAGE) competes with RAGE to bind its ligands, thus potentially preventing RAGE-induced inflammation. METHODS: To investigate whether sRAGE and related genetic variants are associated with colorectal cancer risk, we conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma sRAGE concentrations were measured by ELISA in 1,361 colorectal cancer matched case-control sets. Twenty-four SNPs encoded in the genes associated with sRAGE concentrations were available for 1,985 colorectal cancer cases and 2,220 controls. Multivariable adjusted ORs and 95% confidence intervals (CIs) were computed using conditional and unconditional logistic regression for colorectal cancer risk and circulating sRAGE and SNPs, respectively. RESULTS: Higher sRAGE concentrations were inversely associated with colorectal cancer (ORQ5vs.Q1, 0.77; 95% CI, 0.59-1.00). Sex-specific analyses revealed that the observed inverse risk association was restricted to men (ORQ5vs.Q1, 0.63; 95% CI, 0.42-0.94), whereas no association was observed in women (ORQ5vs.Q1, 1.00; 95% CI, 0.68-1.48; Pheterogeneity for sex = 0.006). Participants carrying minor allele of rs653765 (promoter region of ADAM10) had lower colorectal cancer risk (C vs. T, OR, 0.90; 95% CI, 0.82-0.99). CONCLUSIONS: Prediagnostic sRAGE concentrations were inversely associated with colorectal cancer risk in men, but not in women. An SNP located within ADAM10 gene, pertaining to RAGE shedding, was associated with colorectal cancer risk. IMPACT: Further studies are needed to confirm our observed sex difference in the association and better explore the potential involvement of genetic variants of sRAGE in colorectal cancer development.
Sanikini H, Muller DC, Chadeau-Hyam M, et al., 2020, Anthropometry, body fat composition and reproductive factors and risk of oesophageal and gastric cancer by subtype and subsite in the UK Biobank cohort, PLoS One, Vol: 15, Pages: 1-22, ISSN: 1932-6203
BackgroundObesity has been positively associated with upper gastrointestinal cancers, but prospective data by subtype/subsite are limited. Obesity influences hormonal factors, which may play a role in these cancers. We examined anthropometry, body fat and reproductive factors in relation to oesophageal and gastric cancer by subtype/subsite in the UK Biobank cohort.MethodsAmong 458,713 UK Biobank participants, 339 oesophageal adenocarcinomas, 124 oesophageal squamous cell carcinomas, 137 gastric cardia and 92 gastric non-cardia cancers were diagnosed during a mean of 6.5 years follow-up. Cox models estimated multivariable hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsBody mass index (BMI), hip circumference, waist circumference, waist-to-hip ratio, waist-to-height ratio, total body fat and trunk fat were positively associated with oesophageal adenocarcinoma (highest vs lowest category: HR = 2.33, 95%-CI:1.65–3.28; HR = 1.56, 95%-CI:1.15–2.13; HR = 2.30, 95%-CI:1.47–3.57; HR = 1.71, 95%-CI:1.01–2.90; HR = 2.87, 95%-CI:1.88–4.38; HR = 1.96, 95%-CI:1.30–2.96; HR = 2.34, 95%-CI:1.70–3.22, respectively). Although there were no statistically significant associations in combined sex analyses, BMI (HR = 1.83, 95%-CI:1.00–3.37), waist circumference (HR = 2.21, 95%-CI:1.27–3.84) and waist-to-hip ratio (HR = 1.92, 95%-CI:1.11–3.29) were associated with gastric cardia cancer in men; however, mutual adjustment attenuated the associations for BMI and waist-to-hip ratio. For oesophageal squamous cell carcinoma, statistically significant inverse associations were observed among women for BMI, hip circumference, waist circumference, waist-to-height ratio, total body fat and trunk fat, although they were based on small numbers. In addition, older age at first (HR = 0.44, 95%-CI:0.22–0.88) and last live birth (HR = 0.44, 95%-CI:0.22–0.87) were inversely associated with oesophageal squamous cell carc
Bueno-de-Mesquita B, Cross A, Aune D, et al., 2020, Circulating bilirubin levels and risk of colorectal cancer: serological and Mendelian randomization analyses, BMC Medicine, Vol: 18, Pages: 1-15, ISSN: 1741-7015
BACKGROUND: Bilirubin, a byproduct of hemoglobin breakdown and purported antioxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex.METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5x10-8) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study.RESULTS: The associations between circulating UCB levels and CRC risk differed by sex (Pheterogeneity=0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin, were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12); P=0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06); P=0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, were
Jakszyn P, Cayssials V, Buckland G, et al., 2020, Inflammatory potential of the diet and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, International Journal of Cancer, Vol: 147, Pages: 1027-1039, ISSN: 0020-7136
Pro-inflammatory diets are associated with risk of developing colorectal cancer (CRC), however inconsistencies exist in subsite- and sex-specific associations. The relationship between CRC and combined lifestyle-related factors that contribute towards a low-grade inflammatory profile has not yet been explored. We examined the association between the dietary inflammatory potential and an inflammatory profile and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. This cohort included 476,160 participants followed-up of 14 years and 5,991 incident CRC cases (3,897 colon and 2,094 rectal tumours). Dietary inflammatory potential was estimated using an Inflammatory Score of the Diet (ISD). An Inflammatory Profile Score (IPS) was constructed, incorporating the ISD, physical activity level and abdominal obesity. The associations between the ISD and CRC and IPS and CRC were assessed using multivariable regression models. More pro- inflammatory diets were related to a higher CRC risk, particularly for colon cancer; Hazar Ratio (HR) for highest versus lowest ISD quartile was 1.15 (95% confidence interval (CI) 1.04-1.27) for CRC, 1.24 (95% CI 1.09-1.41) for colon cancer and 0.99 (95% CI 0.83-1.17) for rectal cancer. Associations were more pronounced in men and not significant in women. The IPS was associated with CRC risk, particularly colon cancer among men; HRs for the highest versus lowest IPS were 1.62 (95% CI 1.31- 2.01) for colon cancer overall and 2.11 (95% CI 1.50-2.97) for colon cancer in men. This study shows that more pro-inflammatory diets and a more inflammatory profile are associated with higher risk of CRC, principally colon cancer and in men. This article is protected by copyright. All rights reserved.
Cross A, Robbins E, Pack K, et al., 2020, Long-term colorectal cancer incidence after adenoma removal and the effects of surveillance on incidence: a multicentre, retrospective, cohort study, Gut, Vol: 69, Pages: 1645-1658, ISSN: 0017-5749
Objective Post-polypectomy colonoscopy surveillance aims to prevent colorectal cancer (CRC). The 2002 UK surveillance guidelines define low-, intermediate-, and high-risk groups, recommending different strategies for each. Evidence supporting the guidelines is limited. We examined CRC incidence and effects of surveillance on incidence among each risk group. Design Retrospective study of 33,011 patients who underwent colonoscopy with adenoma removal at 17 UK hospitals, mostly (87%) from 2000–2010. Patients were followed-up through 2016. Cox regression with time-varying covariates was used to estimate effects of surveillance on CRC incidence adjusted for patient, procedural, and polyp characteristics. Standardised incidence ratios (SIRs) compared incidence with that in the general population. Results After exclusions, 28,972 patients were available for analysis; 14,401 (50%) were classed as low-risk, 11,852 (41%) as intermediate-risk, and 2719 (9%) as high-risk. Median follow-up was 9.3 13years. In the low-, intermediate-, and high-risk groups, CRC incidence per 100,000 person-years was 14140 (95%CI 122–162), 221 (195–251), and 366 (295–453), respectively. CRC incidence was 40–50% lower with a single surveillance visit than with none: hazard ratios were 0.56 (0.39–0.80), 0.59 (0.43–0.81), and 0.49 (0.29–0.82) in the low-, intermediate-, and high-risk groups, respectively. Compared with the general population, CRC incidence without surveillance was similar among low-risk (SIR 0.86, 0.73–1.02) and intermediate-risk (1.16, 0.97–1.37) patients, but higher among high-risk patients (1.91, 1.39–2.56).20Conclusion Post-polypectomy surveillance reduces CRC risk. However, even without surveillance, CRC risk in some low-risk and intermediate-risk patients is no higher than in the general population. These patients could be managed by screening rather than surveillance.
Lujan-Barroso L, Botteri E, Caini S, et al., 2020, Menstrual factors, reproductive history, hormone use, and urothelial carcinoma risk: a prospective study in the EPIC cohort, Cancer Epidemiology, Biomarkers and Prevention, Vol: 29, Pages: 1654-1664, ISSN: 1055-9965
BACKGROUND: Urothelial carcinoma is the predominant (95%) bladder cancer subtype in industrialized nations. Animal and epidemiologic human studies suggest that hormonal factors may influence urothelial carcinoma risk. METHODS: We used an analytic cohort of 333,919 women from the European Prospective Investigation into Cancer and Nutrition Cohort. Associations between hormonal factors and incident urothelial carcinoma (overall and by tumor grade, tumor aggressiveness, and non-muscle-invasive urothelial carcinoma) risk were evaluated using Cox proportional hazards models. RESULTS: During a mean of 15 years of follow-up, 529 women developed urothelial carcinoma. In a model including number of full-term pregnancies (FTP), menopausal status, and menopausal hormone therapy (MHT), number of FTP was inversely associated with urothelial carcinoma risk (HR≥5vs1 = 0.48; 0.25-0.90; Ptrend in parous women = 0.010) and MHT use (compared with nonuse) was positively associated with urothelial carcinoma risk (HR = 1.27; 1.03-1.57), but no dose response by years of MHT use was observed. No modification of HRs by smoking status was observed. Finally, sensitivity analyses in never smokers showed similar HR patterns for the number of FTP, while no association between MHT use and urothelial carcinoma risk was observed. Association between MHT use and urothelial carcinoma risk remained significant only in current smokers. No heterogeneity of the risk estimations in the final model was observed by tumor aggressiveness or by tumor grade. A positive association between MTH use and non-muscle-invasive urothelial carcinoma risk was observed. CONCLUSIONS: Our results support that increasing the number of FTP may reduce urothelial carcinoma risk. IMPACT: More detailed studies on parity are needed to understand the possible effects of perinatal hormone changes in urothelial cells.
Wedekind R, Kiss A, Keski-Rahkonen P, et al., 2020, A metabolomic study of red and processed meat intake and acylcarnitine concentrations in human urine and blood, American Journal of Clinical Nutrition, Vol: 112, Pages: 381-388, ISSN: 0002-9165
BACKGROUND: Acylcarnitines (ACs) play a major role in fatty acid metabolism and are potential markers of metabolic dysfunction with higher blood concentrations reported in obese and diabetic individuals. Diet, and in particular red and processed meat intake, has been shown to influence AC concentrations but data on the effect of meat consumption on AC concentrations is limited. OBJECTIVES: To investigate the effect of red and processed meat intake on AC concentrations in plasma and urine using a randomized controlled trial with replication in an observational cohort. METHODS: In the randomized crossover trial, 12 volunteers successively consumed 2 different diets containing either pork or tofu for 3 d each. A panel of 44 ACs including several oxidized ACs was analyzed by LC-MS in plasma and urine samples collected after the 3-d period. ACs that were associated with pork intake were then measured in urine (n = 474) and serum samples (n = 451) from the European Prospective Investigation into Cancer and nutrition (EPIC) study and tested for associations with habitual red and processed meat intake derived from dietary questionnaires. RESULTS: In urine samples from the intervention study, pork intake was positively associated with concentrations of 18 short- and medium-chain ACs. Eleven of these were also positively associated with habitual red and processed meat intake in the EPIC cross-sectional study. In blood, C18:0 was positively associated with red meat intake in both the intervention study (q = 0.004, Student's t-test) and the cross-sectional study (q = 0.033, linear regression). CONCLUSIONS: AC concentrations in urine and blood were associated with red meat intake in both a highly controlled intervention study and in subjects of a cross-sectional study. Our data on the role of meat intake on this important pathway of fatty acid and energy metabolism may help understanding the role of red meat consumption in the etiology of
Butt J, Jenab M, Pawlita M, et al., 2020, Antibody responses to Helicobacter pylori and risk of developing colorectal cancer in a European cohort, Cancer Epidemiology, Biomarkers and Prevention, Vol: 29, Pages: 1475-1481, ISSN: 1055-9965
BACKGROUND: While Helicobacter pylori (H. pylori) is the major cause of gastric cancer, it has also been suggested to be involved in colorectal cancer (CRC) development. However, prospective studies addressing H. pylori and CRC are sparse and inconclusive. We assessed the association of antibody responses to H. pylori proteins with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: We applied H. pylori multiplex serology to measure antibody responses to 13 H. pylori proteins in pre-diagnostic serum samples from 485 CRC cases and 485 matched controls nested within the EPIC study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable conditional logistic regression to estimate the association of H. pylori overall and protein-specific sero-positivity with odds of developing CRC. RESULTS: Fifty-one percent of CRC cases were H. pylori sero-positive compared to 44% of controls resulting in an OR of 1.36 (95% CI: 1.00-1.85). Among the 13 individual H. pylori proteins, the association was driven mostly by sero-positivity to Helicobacter cysteine-rich protein C (HcpC) (OR: 1.66, 95% CI: 1.19-2.30) and Vacuolating cytotoxin A (VacA) (OR: 1.34, 95% CI: 0.99-1.82), the latter being non-statistically significant only in the fully adjusted model. CONCLUSION: In this prospective multi-center European study, antibody responses to H. pylori proteins, specifically HcpC and VacA, were associated with an increased risk of developing CRC. IMPACT: Biological mechanisms for a potential causal role of H. pylori in colorectal carcinogenesis need to be elucidated, and subsequently whether H. pylori eradication may decrease CRC incidence.
Robbins EC, Wooldrage K, Cross AJ, 2020, Is surveillance colonoscopy necessary for all patients with bowel polyps?, BMJ, Vol: 369, Pages: 1-5, ISSN: 1759-2151
Rutter MD, Bretthauer M, Hassan C, et al., 2020, Principles for evaluation of surveillance after removal of colorectal polyps: recommendations from the world endoscopy organization, Gastroenterology, Vol: 158, Pages: 1529-1533.e4, ISSN: 0016-5085
Murphy N, Carreras-Torres R, Song M, et al., 2020, Circulating levels of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 associate with risk of colorectal cancer based on serologic and mendelian randomization analyses, Gastroenterology, Vol: 158, Pages: 1300-1312.e20, ISSN: 0016-5085
BACKGROUND AIMS: 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. METHODS: Serum levels of IGF1 and other proteins 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]) RESULTS: 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 level associated with colorectal cancer risk (hazard ratio per 1 standard deviation increment of IGF1, 1.11; 95% 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 x 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 x 10-5). Colorectal cancer risk was associated with only 1 variant in IGFBP3 (rs11977526
Archambault AN, Su Y-R, Jeon J, et al., 2020, Cumulative burden of colorectal cancer-associated genetic variants is more strongly associated with early-onset vs late-onset cancer, Gastroenterology, Vol: 158, Pages: 1274-1286.e12, ISSN: 0016-5085
BACKGROUND & AIMS: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC. METHODS: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single-nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants. RESULTS: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction=.01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI, 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI, 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction=5.61x10-5). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI, 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI, 2.70-3.00). Sensitivity analyses were consistent with these findings. CONCLUSIONS: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be
Aglago EK, Huybrechts I, Murphy N, et al., 2020, Consumption of fish and long-chain n-3 polyunsaturated fatty acids is associated with reduced risk of colorectal cancer in a large European cohort, Clinical Gastroenterology and Hepatology, Vol: 18, Pages: 654-666.e6, ISSN: 1542-3565
BACKGROUND & AIMS: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. RESULTS: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80-0.96; Ptrend=.005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82-0.98; Ptrend=.009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83-1.00; Ptrend=.016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78-0.95; Ptrend=.010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18-1.45; Ptrend<.001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity=.026). CONCLUSIONS: In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA.
Sanikini H, Muller DC, Sophiea M, et al., 2020, Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, International Journal of Cancer, Vol: 146, Pages: 929-942, ISSN: 0020-7136
Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow‐up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m2: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist‐to‐hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.
Rutter MD, East J, Rees CJ, et al., 2020, British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland/Public Health England post-polypectomy and post-colorectal cancer resection surveillance guidelines, Gut, Vol: 69, Pages: 201-223, ISSN: 0017-5749
These consensus guidelines were jointly commissioned by the British Society of Gastroenterology (BSG), the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and Public Health England (PHE). They provide an evidence-based framework for the use of surveillance colonoscopy and non-colonoscopic colorectal imaging in people aged 18 years and over. They are the first guidelines that take into account the introduction of national bowel cancer screening. For the first time, they also incorporate surveillance of patients following resection of either adenomatous or serrated polyps and also post-colorectal cancer resection. They are primarily aimed at healthcare professionals, and aim to address:Which patients should commence surveillance post-polypectomy and post-cancer resection?What is the appropriate surveillance interval?When can surveillance be stopped? two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10 mm in size or containing any grade of dysplasia, or an adenoma of at least 10 mm in size or containing high-grade dysplasia); or five or more premalignant polyps The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument provided a methodological framework for the guidelines. The BSG's guideline development process was used, which is National Institute for Health and Care Excellence (NICE) compliant.two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10 mm in size or containing any grade of dysplasia, or an adenoma of at least 10 mm in size or containing high-grade dysplasia); or five or more premalignant polyps The key recommendations are that the high-risk criteria for future colorectal cancer (CRC) following polypectomy comprise either:two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10&thin
Ward HA, Murphy N, Weiderpass E, et al., 2019, Gallstones and incident colorectal cancer in a large pan-European cohort study, International Journal of Cancer, Vol: 145, Pages: 1510-1516, ISSN: 0020-7136
Gallstones, a common gastrointestinal condition, can lead to several digestive complications and can result in inflammation. Risk factors for gallstones include obesity, diabetes, smoking and physical inactivity, all of which are known risk factors for colorectal cancer (CRC), as is inflammation. However, it is unclear whether gallstones are a risk factor for CRC. We examined the association between history of gallstones and CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a prospective cohort of over half a million participants from ten European countries. History of gallstones was assessed at baseline using a self-reported questionnaire. The analytic cohort included 334,986 participants; a history of gallstones was reported by 3,917 men and 19,836 women, and incident CRC was diagnosed among 1,832 men and 2,178 women (mean follow-up: 13.6 years). Hazard ratios (HR) and 95% confidence intervals (CI) for the association between gallstones and CRC were estimated using Cox proportional hazards regression models, stratified by sex, study centre and age at recruitment. The models were adjusted for body mass index, diabetes, alcohol intake and physical activity. A positive, marginally significant association was detected between gallstones and CRC among women in multivariable analyses (HR = 1.14, 95%CI 0.99-1.31, p = 0.077). The relationship between gallstones and CRC among men was inverse but not significant (HR = 0.81, 95%CI 0.63-1.04, p = 0.10). Additional adjustment for details of reproductive history or waist circumference yielded minimal changes to the observed associations. Further research is required to confirm the nature of the association between gallstones and CRC by sex.
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