Imperial College London

Professor Amanda Cross

Faculty of MedicineSchool of Public Health

Professor of Cancer Epidemiology
 
 
 
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Contact

 

+44 (0)20 7594 3338amanda.cross

 
 
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Assistant

 

Mr Will Kay +44 (0)20 7594 3350

 
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Location

 

Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

293 results found

Woodfield G, Belluomo I, Laponogov I, Veselkov K, COBRA1 Working Group, Cross AJ, Hanna GB, Boshier PR, Lin GP, Myridakis A, Ayrton O, Španěl P, Vidal-Diez A, Romano A, Martin J, Marelli L, Groves C, Monahan K, Kontovounisios C, Saunders BPet al., 2022, Diagnostic performance of a non-invasive breath test for colorectal cancer: COBRA1 study, Gastroenterology, Vol: 163, Pages: 1447-1449.e8, ISSN: 0016-5085

Journal article

Becerra-Tomas N, Balducci K, Abar L, Aune D, Cariolou M, Greenwood DC, Markozannes G, Nanu N, Vieira R, Giovannucci EL, Gunter MJ, Jackson AA, Kampman E, Lund V, Allen K, Brockton NT, Croker H, Katsikioti D, McGinley-Gieser D, Mitrou P, Wiseman M, Cross AJ, Riboli E, Clinton SK, McTiernan A, Norat T, Tsilidis KK, Chan DSMet al., 2022, Postdiagnosis dietary factors, supplement use and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis, International Journal of Cancer, Pages: 1-19, ISSN: 0020-7136

Little is known about how diet might influence breast cancer prognosis. The current systematic reviews and meta-analyses summarise the evidence on postdiagnosis dietary factors and breast cancer outcomes from randomised controlled trials and longitudinal observational studies. PubMed and Embase were searched through 31st October 2021. Random-effects linear dose-response meta-analysis was conducted when at least three studies with sufficient information were available. The quality of the evidence was evaluated by an independent Expert Panel. We identified 108 publications. No meta-analysis was conducted for dietary patterns, vegetables, wholegrains, fish, meat, and supplements due to few studies, often with insufficient data. Meta-analysis was only possible for all-cause mortality with dairy, isoflavone, carbohydrate, dietary fibre, alcohol intake and serum 25-hydroxyvitamin D (25(OH)D), and for breast cancer-specific mortality with fruit, dairy, carbohydrate, protein, dietary fat, fibre, alcohol intake and serum 25(OH)D. The results, with few exceptions, were generally null. There was limited-suggestive evidence that predefined dietary patterns may reduce the risk of all-cause and other causes of death; that isoflavone intake reduces the risk of all-cause mortality (relative risk (RR) per 2 mg/day: 0.96, 95% confidence interval (CI): 0.92-1.02), breast cancer-specific mortality (RR for high vs low: 0.83, 95% CI: 0.64-1.07), and recurrence (RR for high vs low: 0.75, 95% CI: 0.61-0.92); that dietary fibre intake decreases all-cause mortality (RR per 10 g/day: 0.87, 95% CI: 0.80-0.94); and that serum 25(OH)D is inversely associated with all-cause and breast cancer-specific mortality (RR per 10 nmol/L: 0.93, 95% CI: 0.89-0.97 and 0.94, 95% CI: 0.90-0.99, respectively). The remaining associations were graded as limited-no conclusion.

Journal article

Tsilidis KK, Cariolou M, Becerra-Tomas N, Balducci K, Vieira R, Abar L, Aune D, Markozannes G, Nanu N, Greenwood DC, Giovannucci EL, Gunter MJ, Jackson AA, Kampman E, Lund V, Allen K, Brockton NT, Croker H, Katsikioti D, McGinley-Gieser D, Mitrou P, Wiseman M, Cross AJ, Riboli E, Clinton SK, McTiernan A, Norat T, Chan DSMet al., 2022, Postdiagnosis body fatness, recreational physical activity, dietary factors and breast cancer prognosis: Global Cancer Update Programme (CUP Global) summary of evidence grading, International Journal of Cancer, ISSN: 0020-7136

Based on the Global Cancer Update Programme, formally known as the World Cancer Research Fund/American Institute for Cancer Research Continuous Update Project, we performed systematic reviews and meta-analyses to investigate the association of postdiagnosis body fatness, physical activity and dietary factors with breast cancer prognosis. We searched PubMed and Embase for randomised controlled trials and longitudinal observational studies from inception to 31 October 2021. We calculated summary relative risks (RRs) and 95% confidence intervals (CIs) using random-effects meta-analyses. An independent Expert Panel graded the quality of evidence according to predefined criteria. The evidence on postdiagnosis body fatness and higher all-cause mortality (RR per 5 kg/m2 in body mass index: 1.07, 95% CI: 1.05-1.10), breast cancer-specific mortality (RR: 1.10, 95% CI: 1.06-1.14) and second primary breast cancer (RR: 1.14, 95% CI: 1.04-1.26) was graded as strong (likelihood of causality: probable). The evidence for body fatness and breast cancer recurrence and other nonbreast cancer-related mortality was graded as limited (likelihood of causality: limited-suggestive). The evidence on recreational physical activity and lower risk of all-cause (RR per 10 metabolic equivalent of task-hour/week: 0.85, 95% CI: 0.78-0.92) and breast cancer-specific mortality (RR: 0.86, 95% CI: 0.77-0.96) was judged as limited-suggestive. Data on dietary factors was limited, and no conclusions could be reached except for healthy dietary patterns, isoflavone and dietary fibre intake and serum 25(OH)D concentrations that were graded with limited-suggestive evidence for lower risk of the examined outcomes. Our results encourage the development of lifestyle recommendations for breast cancer patients to avoid obesity and be physically active.

Journal article

Chan DSM, Vieira R, Abar L, Aune D, Balducci K, Cariolou M, Greenwood DC, Markozannes G, Nanu N, Becerra-Tomas N, Giovannucci EL, Gunter MJ, Jackson AA, Kampman E, Lund V, Allen K, Brockton NT, Croker H, Katsikioti D, McGinley-Gieser D, Mitrou P, Wiseman M, Cross AJ, Riboli E, Clinton SK, McTiernan A, Norat T, Tsilidis KKet al., 2022, Postdiagnosis body fatness, weight change and breast cancer prognosis: Global Cancer Update Program (CUP global) systematic literature review and meta-analysis, International Journal of Cancer, ISSN: 0020-7136

Previous evidence on postdiagnosis body fatness and mortality after breast cancer was graded as limited-suggestive. To evaluate the evidence on body mass index (BMI), waist circumference, waist-hip-ratio and weight change in relation to breast cancer prognosis, an updated systematic review was conducted. PubMed and Embase were searched for relevant studies published up to 31 October, 2021. Random-effects meta-analyses were conducted to estimate summary relative risks (RRs). The evidence was judged by an independent Expert Panel using pre-defined grading criteria. One randomized controlled trial and 225 observational studies were reviewed (220 publications). There was strong evidence (likelihood of causality: probable) that higher postdiagnosis BMI was associated with increased all-cause mortality (64 studies, 32 507 deaths), breast cancer-specific mortality (39 studies, 14 106 deaths) and second primary breast cancer (11 studies, 5248 events). The respective summary RRs and 95% confidence intervals per 5 kg/m2 BMI were 1.07 (1.05-1.10), 1.10 (1.06-1.14) and 1.14 (1.04-1.26), with high between-study heterogeneity (I2 = 56%, 60%, 66%), but generally consistent positive associations. Positive associations were also observed for waist circumference, waist-hip-ratio and all-cause and breast cancer-specific mortality. There was limited-suggestive evidence that postdiagnosis BMI was associated with higher risk of recurrence, nonbreast cancer deaths and cardiovascular deaths. The evidence for postdiagnosis (unexplained) weight or BMI change and all outcomes was graded as limited-no conclusion. The RCT showed potential beneficial effect of intentional weight loss on disease-free-survival, but more intervention trials and well-designed observational studies in diverse populations are needed to elucidate the impact of body composition and their changes on breast cancer outcomes.

Journal article

Cariolou M, Abar L, Aune D, Balducci K, Becerra-Tomas N, Greenwood DC, Markozannes G, Nanu N, Vieira R, Giovannucci EL, Gunter MJ, Jackson AA, Kampman E, Lund V, Allen K, Brockton NT, Croker H, Katsikioti D, McGinley-Gieser D, Mitrou P, Wiseman M, Cross AJ, Riboli E, Clinton SK, McTiernan A, Norat T, Tsilidis KK, Chan DSMet al., 2022, Postdiagnosis recreational physical activity and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis, International Journal of Cancer, Pages: 1-16, ISSN: 0020-7136

It is important to clarify the associations between modifiable lifestyle factors such as physical activity and breast cancer prognosis to enable the development of evidence-based survivorship recommendations. We performed a systematic review and meta-analyses to summarise the evidence on the relationship between postbreast cancer diagnosis physical activity and mortality, recurrence and second primary cancers. We searched PubMed and Embase through 31st October 2021 and included 20 observational studies and three follow-up observational analyses of patients enrolled in clinical trials. In linear dose-response meta-analysis of the observational studies, each 10-unit increase in metabolic equivalent of task (MET)-h/week higher recreational physical activity was associated with 15% and 14% lower risk of all-cause (95% confidence interval [CI]: 8%-22%, studies = 12, deaths = 3670) and breast cancer-specific mortality (95% CI: 4%-23%, studies = 11, deaths = 1632), respectively. Recreational physical activity was not associated with breast cancer recurrence (HR = 0.97, 95% CI: 0.91-1.05, studies = 6, deaths = 1705). Nonlinear dose-response meta-analyses indicated 48% lower all-cause and 38% lower breast cancer-specific mortality with increasing recreational physical activity up to 20 MET-h/week, but little further reduction in risk at higher levels. Predefined subgroup analyses across strata of body mass index, hormone receptors, adjustment for confounders, number of deaths, menopause and physical activity intensities were consistent in direction and magnitude to the main analyses. Considering the methodological limitations of the included studies, the independent Expert Panel concluded ‘limited-suggestive’ likelihood of causality for an association between recreational physical activity and lower risk of all-cause and breast cancer-specific mortality.

Journal article

Botteri E, Peveri G, Berstad P, Bagnardi V, Chen SLF, Sandanger TM, Hoff G, Dahm CC, Antoniussen CS, Tjønneland A, Eriksen AK, Skeie G, Perez-Cornago A, Huerta JM, Jakszyn P, Harlid S, Sundström B, Barricarte A, Monninkhof EM, Derksen JWG, Schulze MB, Bueno-de-Mesquita B, Sánchez M-J, Cross AJ, Tsilidis KK, De Magistris MS, Kaaks R, Katzke V, Rothwell JA, Laouali N, Severi G, Amiano P, Contiero P, Sacerdote C, Goldberg M, Touvier M, Freisling H, Viallon V, Weiderpass E, Riboli E, Gunter MJ, Jenab M, Ferrari Pet al., 2022, Changes in lifestyle and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition., Am J Gastroenterol

INTRODUCTION: We investigated the impact of changes in lifestyle habits on colorectal cancer (CRC) risk in a multi-country European cohort. METHODS: We used baseline and follow-up questionnaire data from the EPIC cohort to assess changes in lifestyle habits and their associations with CRC development. We calculated a healthy lifestyle index (HLI) score based on smoking status, alcohol consumption, body mass index and physical activity collected at the two timepoints. HLI ranged from 0 (most unfavourable) to 16 (most favourable). We estimated the association between HLI changes and CRC risk using Cox regression models and reported hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Among 295,865 participants, 2,799 CRC cases were observed over a median of 7.8 years. Median time between questionnaires was 5.7 years. Each unit increase in HLI from the baseline to the follow-up assessment was associated with a statistically significant 3% lower CRC risk. Among participants in the top tertile at baseline (HLI>11), those in the bottom tertile at follow-up (HLI≤9) had a higher CRC risk (HR 1.34; 95%CI 1.02-1.75) than those remaining in the top tertile. Among individuals in the bottom tertile at baseline, those in the top tertile at follow-up had a lower risk (HR 0.77; 95%CI 0.59-1.00) than those remaining in the bottom tertile. DISCUSSION: Improving adherence to a healthy lifestyle was inversely associated with CRC risk, while worsening adherence was positively associated with CRC risk. These results justify and support recommendations for healthy lifestyle changes and healthy lifestyle maintenance for CRC prevention.

Journal article

Juul FE, Cross AJ, Schoen RE, Senore C, Pinsky P, Miller E, Segnan N, Wooldrage K, Wieszczy-Szczepanik P, Armaroli P, Garborg KK, Adami H-O, Hoff G, Kalager M, Bretthauer M, Loberg M, Holme Oet al., 2022, 15-Year Benefits of Sigmoidoscopy Screening on Colorectal Cancer Incidence and Mortality A Pooled Analysis of Randomized Trials, ANNALS OF INTERNAL MEDICINE, ISSN: 0003-4819

Journal article

Mayen A-L, Viallon V, Botteri E, Proust-Lima C, Bagnardi V, Batista V, Cross AJ, Laouali N, MacDonald CJ, Severi G, Katzke V, Bergmann MM, Schulze MB, Tjonneland A, Eriksen AK, Dahm CC, Antoniussen CS, Jakszyn P, Sanchez M-J, Amiano P, Colorado-Yohar SM, Ardanaz E, Travis R, Palli D, Sabina S, Tumino R, Ricceri F, Panico S, Bueno-de-Mesquita B, Derksen JWG, Sonestedt E, Winkvist A, Harlid S, Braaten T, Gram IT, Lukic M, Jenab M, Riboli E, Freisling H, Weiderpass E, Gunter MJ, Ferrari Pet al., 2022, A longitudinal evaluation of alcohol intake throughout adulthood and colorectal cancer risk, European Journal of Epidemiology, Vol: 37, Pages: 915-929, ISSN: 0393-2990

BackgroundAlcohol intake is an established risk factor for colorectal cancer (CRC); however, there is limited knowledge on whether changing alcohol drinking habits during adulthood modifies CRC risk.ObjectiveLeveraging longitudinal exposure assessments on alcohol intake at different ages, we examined the relationship between change in alcohol intake and subsequent CRC risk.MethodsWithin the European Prospective Investigation into Cancer and Nutrition, changes in alcohol intake comparing follow-up with baseline assessments were investigated in relation to CRC risk. The analysis included 191,180, participants and 1530 incident CRC cases, with exclusion of the first three years of follow-up to minimize reverse causation. Trajectory profiles of alcohol intake, assessed at ages 20, 30, 40, 50 years, at baseline and during follow-up, were estimated using latent class mixed models and related to CRC risk, including 407,605 participants and 5,008 incident CRC cases.ResultsMean age at baseline was 50.2 years and the follow-up assessment occurred on average 7.1 years later. Compared to stable intake, a 12 g/day increase in alcohol intake during follow-up was positively associated with CRC risk (HR = 1.15, 95%CI 1.04, 1.25), while a 12 g/day reduction was inversely associated with CRC risk (HR = 0.86, 95%CI 0.78, 0.95). Trajectory analysis showed that compared to low alcohol intake, men who increased their alcohol intake from early- to mid- and late-adulthood by up to 30 g/day on average had significantly increased CRC risk (HR = 1.24; 95%CI 1.08, 1.42), while no associations were observed in women. Results were consistent by anatomical subsite.ConclusionsIncreasing alcohol intake during mid-to-late adulthood raised CRC risk, while reduction lowered risk.

Journal article

Clasen JL, Heath AK, Van Puyvelde H, Huybrechts I, Park JY, Ferrari P, Scelo G, Ulvik A, Midttun Ø, Ueland PM, Overvad K, Eriksen AK, Tjønneland A, Kaaks R, Katzke V, Schulze MB, Palli D, Agnoli C, Chiodini P, Tumino R, Sacerdote C, Zamora-Ros R, Rodriguez-Barranco M, Santiuste C, Ardanaz E, Amiano P, Schmidt JA, Weiderpass E, Gunter M, Riboli E, Cross AJ, Johansson M, Muller DCet 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, Vol: 151, Pages: 708-716, 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.

Journal article

Cross AJ, Robbins EC, Pack K, Stenson I, Kirby PL, Patel B, Rutter M, Veitch AM, Saunders BP, Little M, Gray A, Duffy SW, Wooldrage Ket al., 2022, Colonoscopy surveillance following adenoma removal to reduce the risk of colorectal cancer: a retrospective cohort study, Health Technology Assessment, Vol: 26, Pages: I-+, ISSN: 1366-5278

BackgroundColonoscopy surveillance is recommended for some patients post polypectomy. The 2002 UK surveillance guidelines classify post-polypectomy patients into low, intermediate and high risk, and recommend different strategies for each classification. Limited evidence supports these guidelines.ObjectivesTo examine, for each risk group, long-term colorectal cancer incidence by baseline characteristics and the number of surveillance visits; the effects of interval length on detection rates of advanced adenomas and colorectal cancer at first surveillance; and the cost-effectiveness of surveillance compared with no surveillance.DesignA retrospective cohort study and economic evaluation.SettingSeventeen NHS hospitals.ParticipantsPatients with a colonoscopy and at least one adenoma at baseline.Main outcome measuresLong-term colorectal cancer incidence after baseline and detection rates of advanced adenomas and colorectal cancer at first surveillance.Data sourcesHospital databases, NHS Digital, the Office for National Statistics, National Services Scotland and Public Health England.MethodsCox regression was used to compare colorectal cancer incidence in the presence and absence of surveillance and to identify colorectal cancer risk factors. Risk factors were used to stratify risk groups into higher- and lower-risk subgroups. We examined detection rates of advanced adenomas and colorectal cancer at first surveillance by interval length. Cost-effectiveness of surveillance compared with no surveillance was evaluated in terms of incremental costs per colorectal cancer prevented and per quality-adjusted life-year gained.ResultsOur study included 28,972 patients, of whom 14,401 (50%), 11,852 (41%) and 2719 (9%) were classed as low, intermediate and high risk, respectively. The median follow-up time was 9.3 years. Colorectal cancer incidence was 140, 221 and 366 per 100,000 person-years among low-, intermediate- and high-risk patients, respectively. Attendance at one surveilla

Journal article

Chan SSM, Chen Y, Casey K, Olen O, Ludvigsson JF, Carbonnel F, Oldenburg B, Gunter MJ, Tjønneland A, Grip O, DEFINe-IBD Investigators, Lochhead P, Chan AT, Wolk A, Khalili Het 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.

Journal article

Rothwell JA, Murphy N, Bešević J, Kliemann N, Jenab M, Ferrari P, Achaintre D, Gicquiau A, Vozar B, Scalbert A, Huybrechts I, Freisling H, Prehn C, Adamski J, Cross AJ, Pala VM, Boutron-Ruault M-C, Dahm CC, Overvad K, Gram IT, Sandanger TM, Skeie G, Jakszyn P, Tsilidis KK, Aleksandrova K, Schulze MB, Hughes DJ, van Guelpen B, Bodén S, Sánchez M-J, Schmidt JA, Katzke V, Kühn T, Colorado-Yohar S, Tumino R, Bueno-de-Mesquita B, Vineis P, Masala G, Panico S, Eriksen AK, Tjønneland A, Aune D, Weiderpass E, Severi G, Chajès V, Gunter MJet 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.

Journal article

Cross AJ, Robbins EC, Pack K, Stenson I, Rutter MD, Veitch AM, Saunders BP, Duffy SW, Wooldrage Ket al., 2022, Post-polypectomy surveillance interval and advanced neoplasia detection rates: a multicenter, retrospective cohort study, Endoscopy, Vol: 54, Pages: 948-958, ISSN: 0013-726X

Background Longer post-polypectomy surveillance intervals are associated with increased colorectal neoplasia detection at surveillance in some studies. We investigated this association to inform optimal surveillance intervals.Methods Patients who underwent colonoscopy and post-polypectomy surveillance at 17 UK hospitals were classified as low/high risk by baseline findings. We compared detection rates of advanced adenomas (≥ 10 mm, tubulovillous/villous, high grade dysplasia), high risk findings (HRFs: ≥ 2 serrated polyps/[adenomas] of which ≥ 1 is ≥ 10 mm or has [high grade] dysplasia; ≥ 5 serrated polyps/adenomas; or ≥ 1 nonpedunculated polyp ≥ 20 mm), or colorectal cancer (CRC) at surveillance colonoscopy by surveillance interval (< 18 months, 2, 3, 4, 5, 6 years). Risk ratios (RRs) were estimated using multivariable regression.Results Of 11 214 patients, 7216 (64 %) were low risk and 3998 (36 %) were high risk. Among low risk patients, advanced adenoma, HRF, and CRC detection rates at first surveillance were 7.8 %, 3.7 %, and 1.1 %, respectively. Advanced adenoma detection increased with increasing surveillance interval, reaching 9.8 % with a 6-year interval (P trend < 0.001). Among high risk patients, advanced adenoma, HRF, and CRC detection rates at first surveillance were 15.3 %, 10.0 %, and 1.5 %, respectively. Advanced adenoma and CRC detection rates (P trends < 0.001) increased with increasing surveillance interval; RRs (95 % confidence intervals) for CRC were 1.54 (0.68–3.48), 4.44 (1.95–10.08), and 5.80 (2.51–13.40) with 3-, 4-, and 5-year intervals, respectively, versus an interval of < 18 months.Conclusions Metachronous neoplasia was uncommon among low risk patients, even with long surveillance intervals, supporting recommendations for no surveillance in these patients. For high risk patients, a 3-year surveillance interval would ensure timely CRC detection.

Journal article

Nelson V, Cross AJ, Powell J, Shaw Cet 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

BackgroundRates of cancer survival are increasing, with more people living with and beyond cancer. Lifestyle recommendations for cancer survivors are based largely on extrapolation from cancer prevention recommendations. This feasibility study was designed to investigate diet and physical activity variables linked to primary prevention and digital behaviour change interventions in cancer survivors and delivered by an oncology dietitian to plan for future research.MethodsIn this 2-month feasibility study, participants who had completed treatment for colorectal cancer were invited to complete online food diaries, underwent physical activity assessment, attended fortnightly telephone consultations with an oncology dietitian and completed an evaluation form. The baseline food diaries were used to help participants pick two lifestyle changes to focus on throughout the intervention. Demographic and clinical data were analysed using descriptive statistics.ResultsIn total, 996 patients were screened for eligibility; of these, 78 were eligible to approach and 69 were approached, resulting in 20 participants consenting to take part. Overall, the intervention was acceptable with 65% of participants completing an online food diary and 70% engaging with the dietitian over the telephone. The intervention received good feedback, with 100% of those completing the evaluation form reporting they felt supported and found it helpful.ConclusionsThe present study offers preliminary evidence that a lifestyle intervention delivered by an oncology dietitian using digital behaviour change interventions (DBCIs) to cancer survivors is feasible and accepted by participants and providers.

Journal article

Papadimitriou N, Bouras E, van den Brandt PA, Muller DC, Papadopoulou A, Heath AK, Critselis E, Gunter MJ, Vineis P, Ferrari P, Weiderpass E, Boeing H, Bastide N, Merritt MA, Lopez DS, Bergmann MM, Perez-Cornago A, Schulze M, Skeie G, Srour B, Eriksen AK, Boden S, Johansson I, Nøst TH, Lukic M, Ricceri F, Ericson U, Huerta JM, Dahm CC, Agnoli C, Amiano PE, Tjønneland A, Gurrea AB, Bueno-de-Mesquita B, Ardanaz E, Berntsson J, Sánchez M-J, Tumino R, Panico S, Katzke V, Jakszyn P, Masala G, Derksen JWG, Quirós JR, Severi G, Cross AJ, Riboli E, Tzoulaki I, Tsilidis KKet 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.

Journal article

Cross A, Robbins E, Saunders B, Duffy SW, Wooldrage Ket 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

Journal article

Harewood R, Wooldrage K, Robbins EC, Kinross J, von Wagner C, Cross AJet al., 2022, Adenoma characteristics associated with post-polypectomy proximal colon cancer incidence: a retrospective cohort study, British Journal of Cancer, Vol: 126, 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.

Journal article

Pearson-Stuttard J, Cheng Y, Bennett J, Zhou B, Vamos E, Valabhji J, Cross A, Ezzati M, Gregg Eet 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

Journal article

Cross AJ, Myles J, Greliak P, Hackshaw A, Halloran S, Benton SC, Addison C, Chapman C, Djedovic N, Smith S, Wagner CV, Duffy SW, Raine Ret 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.

Journal article

Mori N, Keski-Rahkonen P, Gicquiau A, Rinaldi S, Dimou N, Harlid S, Harbs J, Van Guelpen B, Aune D, Cross AJ, Tsilidis KK, Severi G, Kvaskoff M, Fournier A, Kaaks R, Fortner RT, Schulze MB, Jakszyn P, Sánchez M-J, Colorado-Yohar SM, Ardanaz E, Travis R, Watts EL, Masala G, Krogh V, Tumino R, Sacerdote C, Panico S, de-Mesquita BB, Gram IT, Waaseth M, Gunter MJ, Murphy Net 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

Journal article

Charvat H, Freisling H, Noh H, Gaudet MM, Gunter MJ, Cross AJ, Tsilidis KK, Tjønneland A, Katzke V, Bergmann M, Agnoli C, Rylander C, Skeie G, Jakszyn P, Rosendahl AH, Sund M, Severi G, Tsugane S, Sawada N, Brenner H, Adami H-O, Weiderpass E, Soerjomataram I, Arnold Met 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.

Journal article

Bretthauer M, Schoen RE, Cross AJ, Pinsky PFet al., 2021, Colorectal cancer screening: randomized trials are essential to support recommendations, Annals of Internal Medicine, Vol: 175, ISSN: 0003-4819

Journal article

Cross A, Robbins E, Pack K, Stenson I, Patel B, Rutter M, Veitch A, Saunders B, Duffy S, Wooldrage Ket 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

Journal article

Woodfield G, Belluomo I, Laponogov I, Veselkov K, Spanel P, Cross AJ, Hanna GBet al., 2021, OFR-7 Breath testing for colorectal polyps and cancer- the colorectal breath analysis1 study (COBRA1), Abstracts of the BSG Annual Meeting, Publisher: BMJ Publishing Group, Pages: A17-A17, ISSN: 0017-5749

Conference paper

Baker JR, Umesh S, Jenab M, Schomburg L, Tjønneland A, Olsen A, Boutron-Ruault M-C, Rothwell JA, Severi G, Katzke V, Johnson T, Schulze MB, Masala G, Agnoli C, Simeon V, Tumino R, Bueno-de-Mesquita HB, Gram IT, Skeie G, Bonet C, Rodriguez-Barranco M, Houerta JM, Gylling B, Van Guelpen B, Perez-Cornago A, Aglago E, Freisling H, Weiderpass E, Cross AJ, Heath AK, Hughes DJ, Fedirko Vet 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.

Journal article

Rothwell JA, Jenab M, Karimi M, Truong T, Mahamat-Saleh Y, Ferrari P, Dashti SG, Kühn T, Cross AJ, Severi G, Gunter MJ, Murphy Net 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.

Journal article

Cross AJ, Robbins EC, 2021, Reply, Clinical Gastroenterology and Hepatology, Vol: 19, Pages: 2217-2218, ISSN: 1542-3565

Journal article

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

Journal article

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.

Journal article

Harewood R, Disney R, Kinross J, von Wagner C, Cross AJet 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.

Journal article

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