284 results found
Rothwell JA, Murphy N, Bešević J, et al., 2022, Metabolic signatures of healthy lifestyle patterns and colorectal cancer risk in a European cohort, Clinical Gastroenterology and Hepatology, Vol: 20, Pages: e1061-e1082, ISSN: 1542-3565
Background & AimsColorectal cancer risk can be lowered by adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines. We derived metabolic signatures of adherence to these guidelines and tested their associations with colorectal cancer risk in the European Prospective Investigation into Cancer cohort.MethodsScores reflecting adherence to the WCRF/AICR recommendations (scale, 1–5) were calculated from participant data on weight maintenance, physical activity, diet, and alcohol among a discovery set of 5738 cancer-free European Prospective Investigation into Cancer participants with metabolomics data. Partial least-squares regression was used to derive fatty acid and endogenous metabolite signatures of the WCRF/AICR score in this group. In an independent set of 1608 colorectal cancer cases and matched controls, odds ratios (ORs) and 95% CIs were calculated for colorectal cancer risk per unit increase in WCRF/AICR score and per the corresponding change in metabolic signatures using multivariable conditional logistic regression.ResultsHigher WCRF/AICR scores were characterized by metabolic signatures of increased odd-chain fatty acids, serine, glycine, and specific phosphatidylcholines. Signatures were inversely associated more strongly with colorectal cancer risk (fatty acids: OR, 0.51 per unit increase; 95% CI, 0.29–0.90; endogenous metabolites: OR, 0.62 per unit change; 95% CI, 0.50–0.78) than the WCRF/AICR score (OR, 0.93 per unit change; 95% CI, 0.86–1.00) overall. Signature associations were stronger in male compared with female participants.ConclusionsMetabolite profiles reflecting adherence to WCRF/AICR guidelines and additional lifestyle or biological risk factors were associated with colorectal cancer. Measuring a specific panel of metabolites representative of a healthy or unhealthy lifestyle may identify strata of the population at higher risk of colorectal cancer.
Chan SSM, Chen Y, Casey K, et al., 2022, Obesity is associated with increased risk of Crohn's disease, but not ulcerative colitis: a pooled analysis of five prospective cohort studies, Clinical Gastroenterology and Hepatology, Vol: 20, Pages: 1048-1058, ISSN: 1542-3565
BACKGROUND AND AIMS: It is unclear whether obesity is associated with the development of inflammatory bowel disease despite compelling data from basic science studies. We therefore examined the association between obesity and risk of Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We conducted pooled analyses of 5 prospective cohorts with validated anthropometric measurements for body mass index (BMI) and waist-hip ratio and other lifestyle factors. Diagnoses of CD and UC were confirmed through medical records or ascertained using validated definitions. We used Cox proportional hazards modeling to calculate pooled multivariable-adjusted HRs (aHRs) and 95% confidence intervals (CIs). RESULTS: Among 601,009 participants (age range, 18-98 years) with 10,110,018 person-years of follow-up, we confirmed 563 incident cases of CD and 1047 incident cases of UC. Obesity (baseline BMI ≥30 kg/m2) was associated with an increased risk of CD (pooled aHR, 1.34; 95% CI, 1.05-1.71, I2 = 0%) compared with normal BMI (18.5 to <25 kg/m2). Each 5 kg/m2 increment in baseline BMI was associated with a 16% increase in risk of CD (pooled aHR, 1.16; 95% CI, 1.05-1.22; I2 = 0%). Similarly, with each 5 kg/m2 increment in early adulthood BMI (age, 18-20 years), there was a 22% increase in risk of CD (pooled aHR, 1.22; 95% CI, 1.05-1.40; I2 = 13.6%). An increase in waist-hip ratio was associated with an increased risk of CD that did not reach statistical significance (pooled aHR across quartiles, 1.08; 95% CI, 0.97-1.19; I2 = 0%). No associations were observed between measures of obesity and risk of UC. CONCLUSIONS: In an adult population, obesity as measured by BMI was associated with an increased risk of older-onset CD but not UC.
Cross AJ, Robbins EC, Pack K, et al., 2022, Post-polypectomy surveillance interval and advanced neoplasia detection rates: a multicenter, retrospective cohort study, ENDOSCOPY, ISSN: 0013-726X
Nelson V, Cross AJ, Powell J, et al., 2022, Can people living with and beyond colorectal cancer make lifestyle changes with the support of health technology: A feasibility study, JOURNAL OF HUMAN NUTRITION AND DIETETICS, ISSN: 0952-3871
Clasen JL, Heath AK, Van Puyvelde H, et al., 2022, Biomarkers of the transsulfuration pathway and risk of renal cell carcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, International Journal of Cancer, ISSN: 0020-7136
Previous studies have suggested that components of one-carbon metabolism, particularly circulating vitamin B6, have an etiological role in renal cell carcinoma (RCC). Vitamin B6 is a cofactor in the transsulfuration pathway. We sought to holistically investigate the role of the transsulfuration pathway in RCC risk. We conducted a nested case-control study (455 RCC cases and 455 matched controls) within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Plasma samples from the baseline visit were analyzed for metabolites of the transsulfuration pathway, including pyridoxal 5'-phosphate (PLP, the biologically active form of vitamin B6), homocysteine, serine, cystathionine, and cysteine, in addition to folate. Bayesian conditional logistic regression was used to estimate associations of metabolites with RCC risk as well as interactions with established RCC risk factors. Circulating PLP and cysteine were inversely associated with RCC risk, and these association were not attenuated after adjustment for other transsulfuration metabolites (odds ratio (OR) and 90% credible interval (CrI) per 1 SD increase in log concentration: 0.76 [0.66, 0.87]; 0.81 [0.66, 0.96], respectively). A comparison of joint metabolite profiles suggested substantially greater RCC risk for the profile representative of low overall transsulfuration function compared with high function (OR 2.70 [90% CrI 1.26, 5.70]). We found some statistical evidence of interactions of cysteine with body mass index, and PLP and homocysteine with smoking status, on their associations with RCC risk. In conclusion, we found evidence suggesting that the transsulfuration pathway may play a role in metabolic dysregulation leading to RCC development. This article is protected by copyright. All rights reserved.
Papadimitriou N, Bouras E, van den Brandt PA, et al., 2022, A prospective diet-wide association study for risk of colorectal cancer in EPIC, Clinical Gastroenterology and Hepatology, Vol: 20, Pages: 864-873.e13, ISSN: 1542-3565
BACKGROUND & AIMS: Evidence regarding the association of dietary exposures with colorectal cancer (CRC) risk is not consistent with a few exceptions. Therefore, we conducted a diet-wide association study (DWAS) in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the associations between several dietary exposures with CRC risk. METHODS: The association of 92 food and nutrient intakes with CRC risk was assessed in 386,792 participants, 5,069 of whom developed incident CRC. Correction for multiple comparisons was performed using the false discovery rate, and emerging associations were examined in the Netherlands Cohort Study (NLCS). Multiplicative gene-nutrient interactions were also tested in EPIC based on known CRC-associated loci. RESULTS: In EPIC, alcohol, liquor/spirits, wine, beer/cider, soft drinks, and pork were positively associated with CRC, whereas milk, cheese, calcium, phosphorus, magnesium, potassium, riboflavin, vitamin B6, beta-carotene, fruit, fibre, non-white bread, banana, and total protein intakes were inversely associated. Of these 20 associations, 13 were replicated in NLCS, for which a meta-analysis was performed, namely alcohol (summary HR per 1 SD increment in intake: 1.07; 95%CI:1.04-1.09), liquor/spirits (1.04; 1.02-1.06), wine (1.04;1.02-1.07), beer/cider (1.06;1.04-1.08), milk (0.95;0.93-0.98), cheese (0.96;0.94-0.99), calcium (0.93;0.90-0.95), phosphorus (0.92;0.90-0.95), magnesium (0.95;0.92-0.98), potassium (0.96;0.94-0.99), riboflavin (0.94;0.92-0.97), beta-carotene (0.96;0.93-0.98), and total protein (0.94;0.92-0.97). None of the gene-nutrient interactions were significant after adjustment for multiple comparisons. CONCLUSIONS: Our findings confirm a positive association for alcohol and an inverse association for dairy products and calcium with CRC risk, and also suggest a lower risk at higher dietary intakes of phosphorus, magnesium, potassium, riboflavin, beta-carotene and total protein.
Cross A, Robbins E, Saunders B, et al., 2022, Higher adenoma detection rates at screening associated with lower long-term colorectal cancer incidence and mortality, Clinical Gastroenterology and Hepatology, Vol: 20, Pages: e148-e67, ISSN: 1542-3565
Background and AimsDetection and removal of adenomas reduces colorectal cancer (CRC) risk. The impact of adenoma detection rates (ADRs) on long-term CRC incidence and mortality is unknown. We investigated this using data from the UK Flexible Sigmoidoscopy Screening Trial (UKFSST).MethodsOf 167,882 UKFSST participants, 40,085 were in the intervention arm and underwent flexible sigmoidoscopy screening at 13 trial centres. Median follow-up was 17 years. At each centre, one endoscopist performed most flexible sigmoidoscopies. Multivariable logistic regression was used to classify centres into high-, intermediate-, and low-detector groups based on their main endoscopist’s ADR. We calculated incidence and mortality of distal and all-site CRC, and estimated hazard ratios (HRs) with 95% confidence intervals (CIs) using Cox regression.ResultsFive, four, and four centres, respectively, were classified into the high-detector, intermediate-detector, and low-detector groups. Average ADRs in each respective group were 15%, 12%, and 9%. Distal CRC incidence and mortality were reduced among those screened compared to controls in all groups, and effects of screening varied significantly by detector ranking, with larger reductions in incidence and mortality seen in the high-detector (incidence: HR=0·34, 0·27–0·42; mortality: HR=0·22, 0·13–0·37) than low-detector group (incidence: HR=0·55, 0·44–0·68; mortality: HR=0·54, 0·34–0·86). Similar results were observed for all-site CRC, with larger effects seen in the high-detector (incidence: HR=0·58, 95%CI 0·50–0·67; mortality: HR=0·52, 0·39–0·69) than low-detector group (incidence: HR=0·72, 0·61–0·85; mortality: HR=0·68, 0·51–0·92), although the heterogeneity was not statistically significant.ConclusionsHigher ADRs at scr
Harewood R, Wooldrage K, Robbins EC, et al., 2022, Adenoma characteristics associated with post-polypectomy proximal colon cancer incidence: a retrospective cohort study, British Journal of Cancer, ISSN: 0007-0920
BackgroundColorectal cancer (CRC) screening is less effective at reducing cancer incidence in the proximal colon compared to the distal colorectum. We aimed to identify adenoma characteristics associated with proximal colon cancer (PCC).MethodsEndoscopy and pathology data for patients with ≥1 adenoma detected at baseline colonoscopy were obtained from 17 UK hospitals between 2001 and 2010. Multivariable Cox regression models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for PCC, and, for comparison, distal CRC incidence, by adenoma characteristics.ResultsAmong 18,431 patients, 152 and 105 developed PCC and distal CRC, respectively, over a median follow-up of 9.8 years. Baseline adenoma characteristics positively associated with PCC incidence included number (≥3 vs. < 3: aHR 2.10, 95% CI: 1.42–3.09), histology (tubulovillous/villous vs. tubular: aHR 1.61, 95% CI: 1.10–2.35) and location (any proximal vs. distal only: aHR 1.70, 95% CI: 1.20–2.42), for which there was borderline evidence of heterogeneity by subsite (p = 0.055). Adenoma dysplasia (high vs. low grade) was associated with distal CRC (aHR 2.42, 95% CI: 1.44–4.04), but not PCC (p-heterogeneity = 0.023).ConclusionsBaseline adenoma number, histology and proximal location were independently associated with PCC and may be important to identify patients at higher risk for post-polypectomy PCC.
Pearson-Stuttard J, Cheng Y, Bennett J, et al., 2022, Trends in leading causes of hospitalisation among adults with diabetes in England from 2003 to 2018: an epidemiological analysis of linked primary care records, The Lancet Diabetes and Endocrinology, Vol: 10, Pages: 46-57, ISSN: 2213-8595
BackgroundDiabetes mellitus (DM) leads to a wide range of established vascular and metabolic complications which has resulted in specific prevention programmes being implemented across high-income countries. DM has been associated with increased risk of a broader set of conditions including cancers, liver disease and common infections. We aimed to examine the trends in a broad set of cause-specific hospitalisations in individuals with DM in England from 2003-2018.MethodsWe identified 309,874 individuals with DM in the Clinical Practice Research Datalink, a well described primary care database, linked to Hospital Episode Statistics inpatient data from 2003-2018. We generated a mixed prevalence and incident DM study population through serial cross sections and follow-up over time. We used a discretised Poisson regression model to estimate annual cause-specific hospitalisation rates in men and women with DM across 17 cause groupings. We generated a 1:1 age and sex matched non-DM population to compare findings. FindingsHospitalisation rates were higher for all causes in persons with DM compared to those without throughout the study period. DM itself and Ischaemic Heart Disease (IHD) were the leading causes of excess hospitalisation in 2003, but by 2018, respiratory conditions, cancers and IHD were the most common causes of excess hospitalisation across men and women. Hospitalisation rates declined in almost all traditional DM complication groupings (IHD, stroke, DM, amputations) whilst generally increasing across broader conditions (cancers, infections, respiratory conditions). These differing trends resulted in a diversification in the cause of hospitalisation, such that the traditional DM complications accounted for more than 50% of hospitalisations in 2003, but only approximately 30% in 2018. In contrast, the portion of hospitalisations that broader conditions accounted for increased including respiratory infections being attributable for 12% of hospitalisations in 2
Cross AJ, Myles J, Greliak P, et al., 2021, Including a general practice endorsement letter with the testing kit in the Bowel Cancer Screening Programme: Results of a cluster randomised trial, Journal of Medical Screening, Vol: 28, Pages: 419-425, ISSN: 0969-1413
OBJECTIVES: To evaluate the effect of general practitioner endorsement accompanying the screening kit rather than with the invitation letter on participation in the NHS Bowel Cancer Screening Programme and on the socioeconomic gradient in participation in the Programme. METHODS: The NHS Bowel Cancer Screening Programme in England is delivered via five regional hubs. In early 2016, we carried out a cluster-randomised trial, with hub-day of invitation as the randomisation unit. We randomised 150 hub-days of invitation to the intervention group, GP endorsement on the letter accompanying the guaiac faecal occult blood testing kit (75 hub-days, 197,366 individuals) or control, usual letter (75 hub-days, 197,476 individuals). The endpoint was participation, defined as return of a valid kit within 18 weeks of initial invitation. Because of the cluster randomisation, data were analysed by a hierarchical logistic regression, allowing a random effect for date of invitation. Socioeconomic status was represented by the index of multiple deprivation. RESULTS: Participation was 59.4% in the intervention group and 58.7% in the control group, a significant difference (p = 0.04). There was no heterogeneity of the effect of intervention by index of multiple deprivation. We found that there was some confounding between date and screening episode order (first or subsequent screen). This in turn may have induced confounding with age and slightly diluted the result. CONCLUSIONS: General practitioner endorsement induces a modest increase in participation in bowel cancer screening, but does not affect the socioeconomic gradient. When considering cluster randomisation as a research method, careful scrutiny of potential confounding is indicated in advance if possible and in analysis otherwise.
Mori N, Keski-Rahkonen P, Gicquiau A, et al., 2021, Endogenous circulating sex hormone concentrations and colon cancer risk in postmenopausal women: a prospective study and meta-analysis, JNCI Cancer Spectrum, Vol: 5, Pages: 1-10, ISSN: 2515-5091
BackgroundObservational studies have consistently reported that postmenopausal hormone therapy use is associated with lower colon cancer risk. However, epidemiological studies examining the associations between circulating concentrations of endogenous estrogens and colorectal cancer have reported inconsistent results.MethodsWe investigated the associations between circulating concentrations of estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA), progesterone, and sex hormone binding globulin (SHBG) with colon cancer risk in a nested case–control study of 1,028 postmenopausal European women (512 colon cancer cases, 516 matched controls) who were non-current users of exogenous hormones at blood collection. Multivariable conditional logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between circulating sex hormones and colon cancer risk. We also conducted a dose-response meta-analysis of prospective studies of circulating estrone and estradiol with colorectal, colon, and rectal cancer risk in postmenopausal women. All statistical tests were 2-sided.ResultsIn the multivariable model, a non-statistically significant positive relationship was found between circulating estrone and colon cancer risk (OR per log2-1 unit increment = 1.17, 95%CI = 1.00–1.38; ORquartile4-quartile1 = 1.33, 95%CI = 0.89–1.97, Ptrend = 0.20). Circulating concentrations of estradiol, free estradiol, testosterone, free testosterone, androstenedione, DHEA, progesterone, and SHBG were not associated with colon cancer risk. In the dose-response meta-analysis, no clear evidence of associations were found between circulating estradiol, and estrone concentrations with colorectal, colon, and rectal cancer risk.ConclusionOur observational and meta-analysis results do not support an association between circulating concentrations of endogenous sex horm
Charvat H, Freisling H, Noh H, et al., 2021, Excess body fatness during early to mid-adulthood and survival from colorectal and breast cancer: a pooled analysis of five international cohort studies, Cancer Epidemiology, Biomarkers and Prevention, Vol: 31, Pages: 325-333, ISSN: 1055-9965
BACKGROUND: Here, we explore the association between excess weight during early to mid-adulthood and survival in patients diagnosed with breast and colorectal cancer, using a pooled analysis of five cohort studies and study participants from 11 countries. METHODS: Participant-level body mass index (BMI) trajectories were estimated by fitting a growth curve model using over 2 million repeated BMI measurements from close to 600,000 cohort participants. Cumulative measures of excess weight were derived. Data from over 23,000 patients with breast and colorectal cancer were subsequently analyzed using time-to-event models for death with the date of diagnosis as start of follow-up. Study-specific results were combined through a random effect meta-analysis. RESULTS: We found a significant dose-response relationship (P trend = 0.013) between the average BMI during early and mid-adulthood and death from breast cancer, with a pooled HR of 1.31 (1.07-1.60) and the time to death shortened by 16% for average BMI above 25 kg/m2 compared with average BMI less than or equal to 22.5 kg/m2, respectively. Similar results were found for categories of cumulative time spent with excess weight. There was no association between excess body fatness during early to mid-adulthood and death in patients with colorectal cancer. CONCLUSIONS: Excess body fatness during early to mid-adulthood is associated not only with an increased risk of developing cancer, but also with a lower survival in patients with breast cancer. IMPACT: Our results emphasize the importance of public health policies aimed at reducing overweight during adulthood and inform future studies on the relationship between excess weight and cancer outcomes.
Bretthauer M, Schoen RE, Cross AJ, et al., 2021, Colorectal cancer screening: randomized trials are essential to support recommendations, Annals of Internal Medicine, Vol: 175, ISSN: 0003-4819
Cross A, Robbins E, Pack K, et al., 2021, Colorectal cancer risk following polypectomy in a multicentre, retrospective, cohort study: an evaluation of the 2020 UK post-polypectomy surveillance guidelines, Gut, Vol: 70, Pages: 2307-2320, ISSN: 0017-5749
Objective:Colonoscopy surveillance aims to reduce colorectal cancer (CRC) incidence post-polypectomy. The 2020 UK guidelines recommend surveillance at three years for ‘high-risk’ patients with ≥2 premalignant polyps (PMPs) of which ≥1 is ‘advanced’ (serrated polyp [or adenoma] ≥10mm or with [high-grade] dysplasia); ≥5 PMPs; or ≥1 non-pedunculated polyp ≥20mm; ‘low-risk’ patients without these findings are instead encouraged to participate in population-based CRC screening. We examined the appropriateness of these risk classification criteria and recommendations.Design:Retrospective analysis of patients who underwent colonoscopy and polypectomy mostly between 2000–2010 at 17 UK hospitals, followed-up through 2017. We examined CRC incidence by baseline characteristics, risk group, and number of surveillance visits using Cox regression, and compared incidence with that in the general population using standardised incidence ratios (SIRs).Results:Among 21,318 patients, 368 CRCs occurred during follow-up (median: 10.1 years). Baseline CRC risk factors included age ≥55 years, ≥2 PMPs, adenomas with tubulovillous/villous/unknown histology or high-grade dysplasia, proximal polyps, and a baseline visit spanning 2–90 days. Compared with the general population, CRC incidence without surveillance was higher among those with adenomas with high-grade dysplasia (SIR:1.74, 95%CI:1.21–2.42) or ≥2 PMPs of which ≥1 was advanced (1.39, 1.09–1.75). For low-risk (71%) and high-risk (29%) patients, SIRs without surveillance were 0.75 (95%CI:0.63–0.88) and 1.30 (1.03–1.62), respectively; for high-risk patients after first surveillance, the SIR was 1.22 (0.91–1.60). Conclusion:These guidelines accurately classify post-polypectomy patients into those at high-risk, for whom one surveillance colonoscopy appears appropriate, and those at low-risk who can be managed by non-invasive screenin
Woodfield G, Belluomo I, Laponogov I, et al., 2021, BREATH TESTING FOR COLORECTAL POLYPS AND CANCER- THE COLORECTAL BREATH ANALYSIS1 STUDY (COBRA1), Publisher: BMJ PUBLISHING GROUP, Pages: A17-A17, ISSN: 0017-5749
Baker JR, Umesh S, Jenab M, et al., 2021, Prediagnostic blood selenium status and mortality among patients with colorectal cancer in Western European populations, Biomedicines, Vol: 9, Pages: 1-15, ISSN: 2227-9059
A higher selenium (Se) status has been shown to be associated with lower risk for colorectal cancer (CRC), but the importance of Se in survival after CRC diagnosis is not well studied. The associations of prediagnostic circulating Se status (as indicated by serum Se and selenoprotein P (SELENOP) measurements) with overall and CRC-specific mortality were estimated using multivariable Cox proportional hazards regression among 995 CRC cases (515 deaths, 396 from CRC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Se and SELENOP serum concentrations were measured on average 46 months before CRC diagnosis. Median follow-up time was 113 months. Participants with Se concentrations in the highest quintile (≥100 µg/L) had a multivariable-adjusted hazard ratio (HR) of 0.73 (95% CI: 0.52–1.02; Ptrend = 0.06) for CRC-specific mortality and 0.77 (95% CI: 0.57–1.03; Ptrend = 0.04) for overall mortality, compared with the lowest quintile (≤67.5 µg/L). Similarly, participants with SELENOP concentrations in the highest (≥5.07 mg/L) compared with the lowest quintile (≤3.53 mg/L) had HRs of 0.89 (95% CI: 0.64–1.24; Ptrend = 0.39) for CRC-specific mortality and 0.83 (95% CI: 0.62–1.11; Ptrend = 0.17) for overall mortality. Higher prediagnostic exposure to Se within an optimal concentration (100–150 µg/L) might be associated with improved survival among CRC patients, although our results were not statistically significant and additional studies are needed to confirm this potential association. Our findings may stimulate further research on selenium’s role in survival among CRC patients especially among those residing in geographic regions with suboptimal Se availability.
Rothwell JA, Jenab M, Karimi M, et al., 2021, Metabolic syndrome and risk of gastrointestinal cancers: an investigation using large-scale molecular data, Clinical Gastroenterology and Hepatology, Vol: 20, ISSN: 1542-3565
BACKGROUND AND AIMS: Gastrointestinal cancer risk is influenced by the presence of metabolic syndrome [MetS]. However, previous epidemiological studies lacked full serological biomarker data for the classification of MetS and the interaction of MetS with germline cancer risk variants is unknown. METHODS: We investigated the associations between MetS and gastrointestinal cancer risk (overall, colorectal, pancreatic, esophageal adenocarcinoma, esophageal squamous cell carcinoma, stomach cardia, stomach non-cardia, hepatocellular carcinoma, and intrahepatic bile duct cancer) in 366,016 UK Biobank participants with comprehensive serum biomarker and genotype data. MetS status was determined by three different definitions at baseline and, in 15,152 participants, at a repeat assessment after a median of 4.3 years of follow-up. Multivariable hazard ratios [HR] and 95% confidence intervals [CI] for cancer outcomes were estimated using Cox proportional hazards models. Analyses stratified by polygenic risk score [PRS] were conducted for colorectal and pancreatic cancers. RESULTS: During a median follow-up of 7.1 years, 4,238 incident cases of a gastrointestinal cancer occurred. MetS at baseline was associated with higher risk of overall gastrointestinal cancer by any definition (HR 1.21, 95% CI 1.13-1.29, harmonized definition). MetS was associated with increased risks of colorectal cancer, colon cancer, rectal cancer, hepatocellular carcinoma, pancreatic cancer in women, and esophageal adenocarcinoma in men. Associations for colorectal cancer and pancreatic cancer did not differ by PRS strata (P-heterogeneity 0.70 and 0.69, respectively), and 80% of participants with MetS at baseline retained this status at the repeat assessment. CONCLUSIONS: These findings underscore the importance of maintaining good metabolic health in reducing the burden of gastrointestinal cancers, irrespective of genetic predisposition.
Cross AJ, Robbins EC, 2021, Reply, Clinical Gastroenterology and Hepatology, Vol: 19, Pages: 2217-2218, ISSN: 1542-3565
Hanna GB, Cross AJ, 2021, Editorial: volatile organic compound analysis to improve faecal immunochemical testing in the detection of colorectal cancer, Alimentary Pharmacology and Therapeutics, Vol: 54, Pages: 504-505, ISSN: 0269-2813
Tsilidis K, 2021, An umbrella review of the evidence associating diet and cancer risk at 11 anatomical sites, Nature Communications, Vol: 12, Pages: 1-10, ISSN: 2041-1723
There is evidence that diet and nutrition are modifiable risk factors for several cancers, but associations may be flawed due to inherent biases. Nutritional epidemiology studies have largely relied on a single assessment of diet using food frequency questionnaires. We conduct an umbrella review of meta-analyses of observational studies to evaluate the strength and validity of the evidence for the association between food/nutrient intake and risk of developing or dying from 11 primary cancers. It is estimated that only few single food/nutrient and cancer associations are supported by strong or highly suggestive meta-analytic evidence, and future similar research is unlikely to change this evidence. Alcohol consumption is positively associated with risk of postmenopausal breast, colorectal, esophageal, head & neck and liver cancer. Consumption of dairy products, milk, calcium and wholegrains are inversely associated with colorectal cancer risk. Coffee consumption is inversely associated with risk of liver cancer and skin basal cell carcinoma.
Harewood R, Disney R, Kinross J, et al., 2021, Medication use and risk of proximal colon cancer: a systematic review of prospective studies with narrative synthesis and meta-analysis, Cancer Causes and Control, Vol: 32, Pages: 1047-1061, ISSN: 0957-5243
PurposeEvidence of differences in the etiology of, and poorer survival from, proximal colon compared to the distal colorectum, necessitates research into its risk factors. This systematic review summarizes the evidence on medication use and proximal colon cancer risk.MethodsMEDLINE and EMBASE were searched for prospective studies investigating nine medication groups, namely non-steroidal anti-inflammatory drugs (NSAIDs), exogenous hormones, i.e., hormone replacement therapy (HRT) or oral contraceptives (OCs), statins, proton pump inhibitors, anti-hypertensives, metformin (an antidiabetic), antidiarrheals or laxatives, and the risk of proximal colon cancer. Narrative synthesis and meta-analyses, using random effects models to estimate risk ratios (RRs) and 95% confidence intervals (CIs), were conducted.ResultsTwenty nine publications investigating NSAIDs (n = 13), exogenous hormones [HRT (n = 9) or OCs (n = 4)] statins (n = 5), anti-hypertensives (n = 1), and metformin (n = 1) were included. Summary RRs reported a protective effect of aspirin use (RR 0.80, 95% CI 0.73–0.89) but no associations between HRT (RR 0.92, 95% CI 0.83–1.02), OC (RR 1.06, 95% CI 0.98–1.14) or statin use (RR 0.94, 95% CI 0.67–1.31), and proximal colon cancer incidence compared to never/non-use. One study on metformin and one on anti-hypertensives reported no association. Sources of between-study heterogeneity included study design, period of exposure ascertainment, exposure source, and exposure comparison, but this exploration was hindered by the small numbers of studies.ConclusionDespite some studies on NSAID or HRT use, evidence on the impact of a range of medications on proximal colon cancer risk is limited. This highlights the need for more research to inform chemoprevention strategies.
Iglesias-Vazquez L, Arija V, Aranda N, et al., 2021, Factors associated with serum ferritin levels and iron excess: results from the EPIC-EurGast study, European Journal of Nutrition, Vol: 61, Pages: 101-114, ISSN: 0044-264X
PurposeExcess iron is involved in the development of non-communicable diseases such as cancer, type 2 diabetes and cardiovascular conditions. We aimed to describe the prevalence of excess iron and its determinants in healthy European adults.MethodsSociodemographic, lifestyle, iron status, dietary information, and HFE genotyping were obtained from controls from the nested case–control study EPIC-EurGast study. High sensitivity C-reactive protein (hsCRP) was measured to address possible systemic inflammation. Descriptive and multivariate analyses were used to assess iron status and its determinants.ResultsOut of the 828 participants (median age: 58.7 years), 43% were females. Median serum ferritin and prevalence of excess iron were 143.7 µg/L and 35.2% in males, respectively, and 77 µg/L and 20% in females, both increasing with latitude across Europe. Prevalence of HFE C282Y mutation was significantly higher in Northern and Central Europe (~ 11%) than in the South (5%). Overweight/obesity, age, and daily alcohol and heme iron intake were independent determinants for iron status, with sex differences even after excluding participants with hsCRP > 5 mg/L. Obese males showed a greater consumption of alcohol, total and red meat, and heme iron, compared with those normal weight.ConclusionObesity, higher alcohol and heme iron consumption were the main risk factors for excess iron in males while only age was associated with iron overload in females. Weight control and promoting healthy lifestyle may help prevent iron overload, especially in obese people. Further research is needed to clarify determinants of excess iron in the healthy adult population, helping to reduce the associated comorbidities.
Dimou N, Mori N, Harlid S, et al., 2021, Circulating Levels of Testosterone, Sex Hormone Binding Globulin and Colorectal Cancer Risk: Observational and Mendelian Randomization Analyses, CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, Vol: 30, Pages: 1336-1348, ISSN: 1055-9965
Clasen J, Heath A, Van Puyvelde H, et al., 2021, A comparison of complementary measures of vitamin B6 status, function, and metabolism in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, American Journal of Clinical Nutrition, Vol: 114, Pages: 338-347, ISSN: 0002-9165
BackgroundVitamin B6 insufficiency has been linked to increased risk of cancer and other chronic diseases. The circulating concentration of pyridoxal 5′-phosphate (PLP) is a commonly used measure of vitamin B6 status. Ratios of substrates indicating PLP coenzymatic function and metabolism may be useful complementary measures to further explore the role of vitamin B6 in health.ObjectivesWe explored the sensitivity of 5 outcomes, namely PLP concentration, homocysteine:cysteine (Hcy:Cys), cystathionine:cysteine (Cysta:Cys), the 3´-hydroxykynurenine ratio (HKr), and the 4-pyridoxic acid ratio (PAr) to vitamin B6 intake as well as personal and lifestyle characteristics.MedthodsDietary intake and biomarker data were collected from participants from 3 nested case-control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC). Bayesian regression models assessed the associations of the 5 biomarker outcomes with vitamin B6 intake and personal and lifestyle covariates. Analogous models examined the relations of Hcy:Cys, Cysta:Cys, and HKr with PLP.ResultsIn total, 4608 participants were included in the analyses. Vitamin B6 intake was most strongly associated with PLP, moderately associated with Hcy:Cys, Cysta:Cys, and HKr, and not associated with PAr (fold change in marker given a doubling of vitamin B6 intake: PLP 1.60 [95% credible interval (CrI): 1.50, 1.71]; Hcy:Cys 0.87 [95% CrI: 0.84, 0.90]; Cysta:Cys 0.89 [95% CrI: 0.84, 0.94]; HKr 0.88 [95% CrI: 0.85, 0.91]; PAr 1.00 [95% CrI: 0.95, 1.05]). PAr was most sensitive to age, and HKr was least sensitive to BMI and alcohol intake. Sex and menopause status were strongly associated with all 5 markers.ConclusionsWe found that 5 different markers, capturing different aspects of vitamin B6–related biological processes, varied in their associations with vitamin B6 intake and personal and lifestyle predictors.
Agudo A, Cayssials V, Bonet C, et al., 2021, Inflammatory potential of the diet & risk of gastric cancer in the European Investigation into Cancer & Nutrition, American Journal of Clinical Nutrition, Vol: 36, Pages: 953-964, ISSN: 1938-3207
The role of chronic inflammation on breast cancer (BC) risk remains unclear beyond as an underlying mechanism of obesity and physical activity. We aimed to evaluate the association between the inflammatory potential of the diet and risk of BC overall, according to menopausal status and tumour subtypes. Within the European Prospective Investigation into Cancer and Nutrition cohort, 318,686 women were followed for 14 years, among whom 13,246 incident BC cases were identified. The inflammatory potential of the diet was characterized by an inflammatory score of the diet (ISD). Multivariable Cox regression models were used to assess the potential effect of the ISD on BC risk by means of hazard ratios (HR) and 95% confidence intervals (CI). ISD was positively associated with BC risk. Each increase of one standard deviation (1-Sd) of the score increased by 4% the risk of BC (HR = 1.04; 95% CI 1.01–1.07). Women in the highest quintile of the ISD (indicating a most pro-inflammatory diet) had a 12% increase in risk compared with those in the lowest quintile (HR = 1.12; 95% CI 1.04–1.21) with a significant trend. The association was strongest among premenopausal women, with an 8% increased risk for 1-Sd increase in the score (HR = 1.08; 95% CI 1.01–1.14). The pattern of the association was quite homogeneous by BC subtypes based on hormone receptor status. There were no significant interactions between ISD and body mass index, physical activity, or alcohol consumption. Women consuming more pro-inflammatory diets as measured by ISD are at increased risk for BC, especially premenopausal women.
Huyghe JR, Harrison TA, Bien SA, et al., 2021, Genetic architectures of proximal and distal colorectal cancer are partly distinct, Gut, Vol: 70, Pages: 1325-1334, ISSN: 0017-5749
OBJECTIVE: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined. DESIGN: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling. RESULTS: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer. CONCLUSION: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
Iguacel I, Schmidt JA, Perez-Cornago A, et al., 2021, Associations between dietary amino acid intakes and blood concentration levels, Clinical Nutrition, Vol: 40, Pages: 3772-3779, ISSN: 0261-5614
BACKGROUND AND AIMS: Emerging evidence suggests a role of amino acids (AAs) in the development of various diseases including renal failure, liver cirrhosis, diabetes and cancer. However, mechanistic pathways and the effects of dietary AA intakes on circulating levels and disease outcomes are unclear. We aimed to compare protein and AA intakes, with their respective blood concentrations in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Dietary protein and AA intakes were assessed via the EPIC dietary questionnaires (DQ) and 24-h dietary recalls (24-HDR). A subsample of 3768 EPIC participants who were free of cancer had blood AA concentrations measured. To investigate how circulating levels relate to their respective intakes, dietary AA intake was examined in quintiles and ANOVA tests were run. Pearson correlations were examined for continous associations between intakes and blood concentrations. RESULTS: Dietary AA intakes (assessed with the DQ) and blood AA concentrations were not strongly correlated (-0.15 ≤ r ≤ 0.17) and the direction of the correlations depended on AA class: weak positive correlations were found for most essential AAs (isoleucine, leucine, lysine, methionine, threonine, tryptophan, and valine) and conditionally essential AAs (arginine and tyrosine), while negative associations were found for non-essential AAs. Similar results were found when using the 24-HDR. When conducting ANOVA tests for essential AAs, higher intake quintiles were linked to higher blood AA concentrations, except for histidine and phenylalanine. For non-essential AAs and glycine, an inverse relationship was observed. Conditionally-essential AAs showed mixed results. CONCLUSIONS: Weak positive correlations and dose responses were found between most essential and conditionally essential AA intakes, and blood concentrations, but not for the non-essential AAs. These results suggest that intake of dietary AA might b
Tsilidis KK, Papadimitriou N, Dimou N, et al., 2021, Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study, American Journal of Clinical Nutrition, Vol: 113, Pages: 1490-1502, ISSN: 0002-9165
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. Genetica
Robbins EC, Cross AJ, 2021, Guaiac fecal occult blood tests and mortality: a 30-year follow-up of two pooled trials, Clinical Gastroenterology and Hepatology, Vol: 19, Pages: 892-894, ISSN: 1542-3565
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.
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