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

 

Room 1089Queen Elizabeth the Queen Mother Wing (QEQM)St Mary's Campus

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Summary

 

Publications

Publication Type
Year
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321 results found

Murphy G, Freedman ND, Abnet CC, Albanes D, Cross AJ, Huang W-Y, Koshiol J, McGlynn K, Parisi D, Männistö S, Weinstein SJ, Waterboer T, Butt J, Murphy Get al., 2024, Helicobacter hepaticus and Helicobacter bilis in liver and biliary cancers from ATBC and PLCO, Helicobacter (Oxford), Vol: 29, ISSN: 1083-4389

Background:Helicobacter species (spp.) have been detected in human bile and hepatobiliary tissue Helicobacter spp. promote gallstone formation and hepatobiliary tumors in laboratory studies, though it remains unclear whether Helicobacter spp. contribute to these cancers in humans. We used a multiplex panel to assess whether seropositivity to Helicobacter (H.) hepaticus or H. bilis proteins was associated with the development of hepatobiliary cancers in the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, and US-based Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO).Methods:We included 62 biliary and 121 liver cancers, and 190 age-matched controls from ATBC and 74 biliary and 105 liver cancers, and 364 age- and sex-matched controls from PLCO. Seropositivity to 14 H. hepaticus and H. bilis antigens was measured using a multiplex assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for major hepatobiliary cancer risk factors and Helicobacter pylori serostatus.Results:Seropositivity to the H. bilis antigen, P167D, was associated with more than a twofold higher risk of liver cancer (OR: 2.38; 95% CI: 1.06, 5.36) and seropositivity to the H. hepaticus antigens HH0407 or HH1201, or H. bilis antigen, HRAG 01470 were associated with higher risk of biliary cancer (OR: 5.01; 95% CI: 1.53, 16.40; OR: 2.40; 95% CI: 1.00, 5.76; OR: 3.27; 95% CI: 1.14, 9.34, respectively) within PLCO. No associations for any of the H. hepaticus or H. bilis antigens were noted for liver or biliary cancers within ATBC.Conclusions:Further investigations in cohort studies should examine the role of Helicobacter spp. in the etiology of liver and biliary cancers.

Journal article

Meyer A, Dong C, Chan SSM, Touvier M, Julia C, Huybrechts I, Nicolas G, Oldenburg B, Heath AK, Tong TYN, Key TJ, Tjønneland A, Kyrø C, Kaaks R, Katzke VA, Bergman MM, Palli D, Masala G, Tumino R, Sacerdote C, ColoradoYohar SM, Sánchez M, Guevara M, Grip O, Holmgren J, Cross A, Karling P, Hultdin J, Murphy N, DeschasauxTanguy M, Hercberg S, Galan P, MahamatSaleh Y, Amiot A, Gunter MJ, BoutronRuault M, Carbonnel Fet al., 2024, Dietary index based on the Food Standards Agency nutrient profiling system and risk of Crohn's disease and ulcerative colitis, Alimentary Pharmacology & Therapeutics, Vol: 59, Pages: 558-568, ISSN: 0269-2813

Background:Nutri-score is now widely available in food packages in Europe.Aim:To study the overall nutritional quality of the diet in relation to risks of Crohn's disease (CD) and ulcerative colitis (UC), in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohortMethods:We collected dietary data at baseline from validated food frequency questionnaires. We used a dietary index based on the UK Food Standards Agency modified nutrient profiling system (FSAm-NPS-DI) underlying the Nutri-Score label, to measure the nutritional quality of the diet. We estimated the association between FSAm-NPS-DI score, and CD and UC risks using Cox models stratified by centre, sex and age; and adjusted for smoking status, BMI, physical activity, energy intake, educational level and alcohol intake.Results:We included 394,255 participants (68.1% women; mean age at recruitment 52.1 years). After a mean follow-up of 13.6 years, there were 184 incident cases of CD and 459 incident cases of UC. Risk of CD was higher in those with a lower nutritional quality, that is higher FSAm-NPS-DI Score (fourth vs. first quartile: aHR: 2.04, 95% CI: 1.24–3.36; p-trend: <0.01). Among items of the FSAm-NPS-DI Score, low intakes of dietary fibre and fruits/vegetables/legumes/nuts were associated with higher risk of CD. Nutritional quality was not associated with risk of UC (fourth vs. first quartile of the FSAm-NPS-DI Score: aHR: 0.91, 95% CI: 0.69–1.21; p-trend: 0.76).Conclusions:A diet with low nutritional quality as measured by the FSAm-NPS-DI Score is associated with a higher risk of CD but not UC.

Journal article

Power S, Wooldrage K, Saunders BP, Cross AJet al., 2024, The impact of endoscopist performance and patient factors on distal adenoma detection and colorectal cancer incidence, BMC Gastroenterology, Vol: 24, ISSN: 1471-230X

Background:High quality endoscopy is key for detecting and removing precursor lesions to colorectal cancer (CRC). Adenoma detection rates (ADRs) measure endoscopist performance. Improving other components of examinations could increase adenoma detection.Aims:To investigate how endoscopist performance at flexible sigmoidoscopy (FS) affects adenoma detection and CRC incidence.Methods:Among 34,139 participants receiving FS screening by the main endoscopist at one of 13 centres in the UK FS Screening Trial, median follow-up was 17 years. Factors examined included family history of CRC, bowel preparation quality, insertion and withdrawal time, bowel segment reached, patient pain and ADR. Odds ratios (OR) for distal adenoma detection were estimated by logistic regression. Hazard ratios (HR) for distal CRC incidence were estimated by Cox regression.Results:At screening, 4,104 participants had distal adenomas detected and 168 participants developed distal CRC during follow-up. In multivariable models, a family history of CRC (yes vs. no: OR 1.40, 95%CI 1.21–1.62), good or adequate bowel preparation quality (vs. excellent: OR 0.84, 95%CI 0.74–0.95; OR 0.56, 95%CI 0.49–0.65, respectively) and longer insertion and withdrawal times (≥ 4.00 vs. < 2.00 min: OR 1.96, 95%CI 1.68–2.29; OR 32.79, 95%CI 28.22–38.11, respectively) were associated with adenoma detection. Being screened by endoscopists with low or intermediate ADRs, compared to high ADRs, was positively associated with CRC incidence (multivariable: HR 4.71, 95%CI 2.65–8.38; HR 2.16, 95%CI 1.22–3.81, respectively).Conclusions:Bowel preparation quality and longer insertion and withdrawal time are key for improving distal adenoma detection. Higher ADRs were associated with a lower risk of distal CRC.

Journal article

Pham TT, Nimptsch K, Aleksandrova K, Jenab M, Fedirko V, Wu K, Eriksen AK, Tjønneland A, Severi G, Rothwell J, Kaaks R, Katzke V, Catalano A, Agnoli C, Masala G, De Magistris MS, Tumino R, Vermeulen R, Aizpurua A, Trobajo-Sanmartín C, Chirlaque M-D, Sánchez M-J, Lu SSM, Cross AJ, Christakoudi S, Weiderpass E, Pischon Tet al., 2024, Pre-diagnostic circulating resistin concentrations and mortality among individuals with colorectal cancer: results from the European Prospective Investigation into Cancer and Nutrition study, International Journal of Cancer, ISSN: 0020-7136

Resistin is a protein involved in inflammation and angiogenesis processes and may play a role in the progression of colorectal cancer (CRC). However, it remains unclear whether resistin is associated with increased mortality after CRC diagnosis. We examined pre-diagnostic serum resistin concentrations in relation to CRC-specific and all-cause mortality among 1343 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. For CRC-specific mortality as the primary outcome, hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated from competing risk analyses based on cause-specific Cox proportional hazards models and further in sensitivity analyses using Fine-Gray proportional subdistribution hazards models. For all-cause mortality as the secondary outcome, Cox proportional hazards models were used. Subgroup analyses were performed by sex, tumor subsite, tumor stage, body mass index and time to CRC diagnosis. Resistin was measured on a median of 4.8 years before CRC diagnosis. During a median follow-up of 8.2 years, 474 deaths from CRC and 147 deaths from other causes were observed. Resistin concentrations were not associated with CRC-specific mortality (HRQ4vsQ1  = 0.95, 95% CI: 0.73-1.23; Ptrend  = .97; and HRper doubling of resistin concentration  = 1.00; 95% CI: 0.84-1.19; P = .98) or all-cause mortality. Results from competing risk (sensitivity) analysis were similar. No associations were found in any subgroup analyses. These findings suggest no association between pre-diagnostic circulating resistin concentrations and CRC-specific or all-cause mortality among persons with CRC, and the potential insignificance of resistin in CRC progression.

Journal article

Botteri E, Peveri G, Berstad P, Bagnardi V, Hoff G, Heath AK, Cross AJ, Vineis P, Dossus L, Johansson M, Freisling H, Matta K, Huybrechts I, Chen SLF, B Borch K, Sandanger TM, H Nøst T, Dahm CC, Antoniussen CS, Tin Tin S, Fournier A, Marques C, Artaud F, Sánchez M-J, Guevara M, Santiuste C, Agudo A, Bajracharya R, Katzke V, Ricceri F, Agnoli C, Bergmann MM, Schulze MB, Panico S, Masala G, Tjønneland A, Olsen A, Stocks T, Manjer J, Aizpurua-Atxega A, Weiderpass E, Riboli E, Gunter MJ, Ferrari Pet al., 2024, Lifestyle changes in middle age and risk of cancer: evidence from the European Prospective Investigation into Cancer and Nutrition, European Journal of Epidemiology, ISSN: 0393-2990

In this study, we aimed to provide novel evidence on the impact of changing lifestyle habits on cancer risk. In the EPIC cohort, 295,865 middle-aged participants returned a lifestyle questionnaire at baseline and during follow-up. At both timepoints, we calculated a healthy lifestyle index (HLI) score based on cigarette smoking, alcohol consumption, body mass index and physical activity. HLI ranged from 0 (most unfavourable) to 16 (most favourable). We estimated the association between HLI change and risk of lifestyle-related cancers-including cancer of the breast, lung, colorectum, stomach, liver, cervix, oesophagus, bladder, and others-using Cox regression models. We reported hazard ratios (HR) with 95% confidence intervals (CI). Median time between the two questionnaires was 5.7 years, median age at follow-up questionnaire was 59 years. After the follow-up questionnaire, we observed 14,933 lifestyle-related cancers over a median follow-up of 7.8 years. Each unit increase in the HLI score was associated with 4% lower risk of lifestyle-related cancers (HR 0.96; 95%CI 0.95-0.97). Among participants in the top HLI third at baseline (HLI > 11), those in the bottom third at follow-up (HLI ≤ 9) had 21% higher risk of lifestyle-related cancers (HR 1.21; 95%CI 1.07-1.37) than those remaining in the top third. Among participants in the bottom HLI third at baseline, those in the top third at follow-up had 25% lower risk of lifestyle-related cancers (HR 0.75; 95%CI 0.65-0.86) than those remaining in the bottom third. These results indicate that lifestyle changes in middle age may have a significant impact on cancer risk.

Journal article

Rashid T, Bennett JE, Muller DC, Cross AJ, Pearson-Stuttard J, Asaria P, Daby HI, Fecht D, Davies B, Ezzati M, Rashid T, Bennett JE, Muller D, Cross A, Pearson-Stuttard J, Daby H, Fecht D, Davies B, Ezzati Met al., 2024, Mortality from leading cancers in districts of England from 2002 to 2019: a population-based, spatiotemporal study, The Lancet Oncology, Vol: 25, Pages: 86-98, ISSN: 1213-9432

BACKGROUND: Cancers are the leading cause of death in England. We aimed to estimate trends in mortality from leading cancers from 2002 to 2019 for the 314 districts in England. METHODS: We did a high-resolution spatiotemporal analysis of vital registration data from the UK Office for National Statistics using data on all deaths from the ten leading cancers in England from 2002 to 2019. We used a Bayesian hierarchical model to obtain robust estimates of age-specific and cause-specific death rates. We used life table methods to calculate the primary outcome, the unconditional probability of dying between birth and age 80 years by sex, cancer cause of death, local district, and year. We reported Spearman rank correlations between the probability of dying from a cancer and district-level poverty in 2019. FINDINGS: In 2019, the probability of dying from a cancer before age 80 years ranged from 0·10 (95% credible interval [CrI] 0·10-0·11) to 0·17 (0·16-0·18) for women and from 0·12 (0·12-0·13) to 0·22 (0·21-0·23) for men. Variation in the probability of dying was largest for lung cancer among women, being 3·7 times (95% CrI 3·2-4·4) higher in the district with the highest probability than in the district with the lowest probability; and for stomach cancer for men, being 3·2 times (2·6-4·1) higher in the district with the highest probability than in the one with the lowest probability. The variation in the probability of dying was smallest across districts for lymphoma and multiple myeloma (95% CrI 1·2 times [1·1-1·4] higher in the district with the highest probability than the lowest probability for women and 1·2 times [1·0-1·4] for men), and leukaemia (1·1 times [1·0-1·4] for women and 1·2 times [1·0-1·5] for men). The Spearman rank correlation between probability

Journal article

Sanikini H, Biessy C, Rinaldi S, Navionis A-S, Gicquiau A, Keski-Rahkonen P, Kiss A, Weinstein SJ, Albanes D, Agudo A, Jenab M, Riboli E, Gunter MJ, Murphy G, Cross AJet al., 2023, Circulating hormones and risk of gastric cancer by subsite in three cohort studies, Gastric Cancer, Vol: 26, Pages: 969-987, ISSN: 1436-3305

BackgroundObesity has been positively associated with gastric cancer. Excess fat impacts hormones, which have been implicated in carcinogenesis. We investigated obesity-related hormones and cardia gastric cancer (CGC) and non-cardia gastric cancer (NCGC) risk.MethodsNested case–control studies were conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (61 CGCs, and 172 NCGCs and matched controls) and the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) study (100 CGCs and 65 NCGCs and matched controls); serum hormones were measured. In UK-Biobank (n = 458,713), we included 137 CGCs and 92 NCGCs. Sex-specific analyses were conducted. For EPIC and ATBC, odds ratios (ORs), and for UK-Biobank hazard ratios (HRs), were estimated using conditional logistic regression and Cox regression, respectively.ResultsInsulin-like growth-factor-1 was positively associated with CGC and NCGC in EPIC men (ORper 1-SD increase 1.94, 95% CI 1.03–3.63; ORper 1-SD increase 1.63, 95% CI 1.05–2.53, respectively), with similar findings for CGC in UK-Biobank women (HRper 1-SD increase 1.76, 95% CI 1.08–2.88). Leptin in EPIC men and C-peptide in EPIC women were positively associated with NCGC (ORT3 vs. T1 2.72, 95% CI 1.01–7.34 and ORper 1-SD increase 2.17, 95% CI 1.19–3.97, respectively). Sex hormone-binding globulin was positively associated with CGC in UK-Biobank men (HRper 1-SD increase 1.29, 95% CI 1.02–1.64). Conversely, ghrelin was inversely associated with NCGC among EPIC and ATBC men (ORper 1-SD increase 0.53, 95% CI 0.34–0.84; ORper 1-SD increase 0.22, 95% CI 0.10–0.50, respectively). In addition, dehydroepiandrosterone was inversely associated with CGC in EPIC and ATBC men combined.ConclusionsSome obesity-related hormones influence CGC and NCGC risk.

Journal article

Guller ZE, Harewood RN, Weiderpass E, Huybrechts I, Jenab M, Huerta JM, Sanchez M-J, Jakszyn P, Amiano P, Ardanaz E, Agnoli C, Tumino R, Palli D, Skeie G, Manjer J, Papier K, Tjonneland A, Eriksen AK, Schulze MB, Kaaks R, Katzke V, Bergmann MM, Riboli E, Gunter MJ, Cross AJet al., 2023, Diet and lifestyle in relation to small intestinal cancer risk: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC), Cancer Causes and Control, Vol: 34, Pages: 927-937, ISSN: 0957-5243

PurposeThe incidence of small intestinal cancer (SIC) is increasing, however, its aetiology remains unclear due to a lack of data from large-scale prospective cohorts. We examined modifiable risk factors in relation to SIC overall and by histological subtype.MethodsWe analysed 450,107 participants enrolled in the European Prospective Investigation into Cancer and Nutrition cohort. Cox proportional hazards models were used to estimate univariable and multivariable hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsDuring an average of 14.1 years of follow-up, 160 incident SICs (62 carcinoids, 51 adenocarcinomas) were identified. Whilst univariable models revealed a positive association for current versus never smokers and SIC (HR, 95% CI: 1.77, 1.21–2.60), this association attenuated in multivariable models. In energy-adjusted models, there was an inverse association across vegetable intake tertiles for SIC overall (HRT3vsT1, 95% CI: 0.48, 0.32–0.71, p-trend: < 0.001) and for carcinoids (HRT3vsT1, 95% CI: 0.44, 0.24–0.82, p-trend: 0.01); however, these attenuated in multivariable models. Total fat was also inversely associated with total SIC and both subtypes but only in the second tertile (SIC univariable HRT2vsT1, 95% CI: 0.57, 0.38–0.84; SIC multivariable HRT2vsT1, 95% CI: 0.55, 0.37–0.81). Physical activity, intake of alcohol, red or processed meat, dairy products, or fibre were not associated with SIC.ConclusionThese exploratory analyses found limited evidence for a role of modifiable risk factors in SIC aetiology. However, sample size was limited, particularly for histologic subtypes; therefore, larger studies are needed to delineate these associations and robustly identify risk factors for SIC.

Journal article

Clasen JL, Mabunda R, Heath AK, Kaaks R, Katzke V, Schulze MB, Birukov A, Tagliabue G, Chiodini P, Tumino R, Milani L, Braaten T, Gram I, Lukic M, LujánBarroso L, RodriguezBarranco M, Chirlaque M, Ardanaz E, Amiano P, Manjer J, Huss L, Ljungberg B, Travis R, SmithByrne K, Gunter M, Johansson M, Rinaldi S, Weiderpass E, Riboli E, Cross AJ, Muller DCet al., 2023, Reproductive and hormonal factors and risk of renal cell carcinoma among women in the European Prospective Investigation into Cancer and Nutrition, Cancer Medicine, Vol: 12, Pages: 15588-15600, ISSN: 2045-7634

BackgroundRenal cell carcinoma (RCC) is twice as common among men compared with women, and hormonal factors have been suggested to partially explain this difference. There is currently little evidence on the roles of reproductive and hormonal risk factors in RCC aetiology.Materials & MethodsWe investigated associations of age at menarche and age at menopause, pregnancy-related factors, hysterectomy and ovariectomy and exogenous hormone use with RCC risk among 298,042 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.ResultsDuring 15 years of follow-up, 438 RCC cases were identified. Parous women had higher rates of RCC compared with nulliparous women (HR = 1.71, 95% CI 1.18, 2.46), and women who were older at age of first pregnancy had lower rates of RCC (30 years + vs. <20 years HR = 0.53, 95% CI 0.34, 0.82). Additionally, we identified a positive association for hysterectomy (HR = 1.43 95% CI 1.09, 1.86) and bilateral ovariectomy (HR = 1.67, 95% CI 1.13, 2.47), but not unilateral ovariectomy (HR = 0.99, 95% CI 0.61, 1.62) with RCC risk. No clear associations were found for age at menarche, age at menopause or exogenous hormone use.ConclusionOur results suggest that parity and reproductive organ surgeries may play a role in RCC aetiology.

Journal article

Lim J, Hong HGG, Weinstein SJ, Playdon MC, Cross AJ, Stolzenberg-Solomon R, Freedman ND, Huang J, Albanes Det al., 2023, Metabolomic analysis of vitamin E supplement use in the prostate, lung, colorectal, and ovarian cancer screening trial, Nutrients, Vol: 15, ISSN: 2072-6643

The effects of vitamin E supplementation on cancer and other chronic diseases are not clear. We compared the serum metabolomic profile of differing vitamin E dosages in order to re-examine the previously observed changes in a novel C22 lactone sulfate compound, androgenic steroids, and other metabolites. A total of 3409 women and men previously selected for metabolomics studies in the PLCO Cancer Screening Trial were included in this investigation. Serum metabolites were profiled using ultrahigh-performance liquid and gas chromatography/tandem mass spectrometry. Seventy known metabolites including C22 lactone sulfate and androgens were significantly associated with vitamin E supplementation. In the sex-stratified analysis, 10 cofactors and vitamins (e.g., alpha-CEHC sulfate and alpha-CEHC glucuronide), two carbohydrates (glyceric and oxalic acids), and one lipid (glycocholenate sulfate) were significantly associated with vitamin E dose in both males and females (FDR-adjusted p-value < 0.01). However, the inverse association between C22 lactone sulfate and daily vitamin E supplementation was evident in females only, as were two androgenic steroids, 5-androstenediol and androsterone glucuronide. Our study provides evidence of distinct steroid hormone pathway responses based on vitamin E dosages. Further studies are needed to gain biological insights into vitamin E biochemical effects relevant to cancer and other chronic diseases.

Journal article

Juul FE, Cross AJ, Pinsky P, Senore C, Loberg Met al., 2023, 15-year benefits of sigmoidoscopy screening on colorectal cancer incidence and mortality a pooled analysis of randomized trials response, Annals of Internal Medicine, Vol: 176, ISSN: 0003-4819

Journal article

Lopes EW, Chan SSM, Song M, Ludvigsson JF, Hakansson N, Lochhead P, Clark A, Burke KE, Ananthakrishnan AN, Cross AJ, Palli D, Bergmann MM, Richter JM, Chan AT, Olen O, Wolk A, Khalili Het al., 2023, Lifestyle factors for the prevention of inflammatory bowel disease, Gut, Vol: 72, Pages: 1093-1100, ISSN: 0017-5749

Objective To estimate the proportion of cases of Crohn’s disease (CD) and ulcerative colitis (UC) that could be prevented by modifiable lifestyle factors.Design In a prospective cohort study of US adults from the Nurses’ Health Study (NHS; n=72 290), NHSII (n=93 909) and Health Professionals Follow-up Study (HPFS; n=41 871), we created modifiable risk scores (MRS; 0–6) for CD and UC based on established lifestyle risk factors, and healthy lifestyle scores (HLS; 0–9) derived from American healthy lifestyle recommendations. We calculated the population attributable risk by comparing the incidence of CD and UC between low-risk (CD-MRS≤1, UC-MRS≤2, HLS≥7) and high-risk groups. We externally validated our findings in three European cohorts: the Swedish Mammography Cohort (n=37 275), Cohort of Swedish Men (n=40 810) and European Prospective Investigation into Cancer and Nutrition (n=404 144).Results Over 5 117 021 person-years of follow-up (NHS, HPFS: 1986–2016; NHSII: 1991–2017), we documented 346 CD and 456 UC cases. Adherence to a low MRS could have prevented 42.9% (95% CI 12.2% to 66.1%) of CD and 44.4% (95% CI 9.0% to 69.8%) of UC cases. Similarly, adherence to a healthy lifestyle could have prevented 61.1% (95% CI 16.8% to 84.9%) of CD and 42.2% (95% CI 1.7% to 70.9%) of UC cases. In our validation cohorts, adherence to a low MRS and healthy lifestyle could have, respectively, prevented 43.9%–51.2% and 48.8%–60.4% of CD cases and 20.6%–27.8% and 46.8%–56.3% of UC cases.Conclusions Across six US and European cohorts, a substantial burden of inflammatory bowel diseases risk may be preventable through lifestyle modification.

Journal article

Aglago EK, Cross AJ, Riboli E, Fedirko V, Hughes DJ, Fournier A, Jakszyn P, Freisling H, Gunter MJ, Dahm CC, Overvad K, Tjønneland A, Kyrø C, Boutron-Ruault M-C, Rothwell JA, Severi G, Katzke V, Srour B, Schulze MB, Wittenbecher C, Palli D, Sieri S, Pasanisi F, Tumino R, Ricceri F, Bueno-de-Mesquita B, Derksen JWG, Skeie G, Jensen TE, Lukic M, Sánchez M-J, Amiano P, Colorado-Yohar S, Barricarte A, Ericson U, van Guelpen B, Papier K, Knuppel A, Casagrande C, Huybrechts I, Heath AK, Tsilidis KK, Jenab Met al., 2023, Dietary intake of total, heme and non-heme iron and the risk of colorectal cancer in a European prospective cohort study, British Journal of Cancer, Vol: 128, Pages: 1529-1540, ISSN: 0007-0920

BackgroundIron is an essential micronutrient with differing intake patterns and metabolism between men and women. Epidemiologic evidence on the association of dietary iron and its heme and non-heme components with colorectal cancer (CRC) development is inconclusive.MethodsWe examined baseline dietary questionnaire-assessed intakes of total, heme, and non-heme iron and CRC risk in the EPIC cohort. Sex-specific multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox regression. We modelled substitution of a 1 mg/day of heme iron intake with non-heme iron using the leave one-out method.ResultsOf 450,105 participants (318,680 women) followed for 14.2 ± 4.0 years, 6162 (3511 women) developed CRC. In men, total iron intake was not associated with CRC risk (highest vs. lowest quintile, HRQ5vs.Q1:0.88; 95%CI:0.73, 1.06). An inverse association was observed for non-heme iron (HRQ5vs.Q1:0.80, 95%CI:0.67, 0.96) whereas heme iron showed a non-significant association (HRQ5vs.Q1:1.10; 95%CI:0.96, 1.27). In women, CRC risk was not associated with intakes of total (HRQ5vs.Q1:1.11, 95%CI:0.94, 1.31), heme (HRQ5vs.Q1:0.95; 95%CI:0.84, 1.07) or non-heme iron (HRQ5vs.Q1:1.03, 95%CI:0.88, 1.20). Substitution of heme with non-heme iron demonstrated lower CRC risk in men (HR:0.94; 95%CI: 0.89, 0.99).ConclusionsOur findings suggest potential sex-specific CRC risk associations for higher iron consumption that may differ by dietary sources.

Journal article

Ezzati M, Mishra A, Zhou B, Rodriguez-Martinez A, Bixby H, Singleton R, Carrillo-Larco R, Sheffer K, Paciorek C, Bennett J, Lhoste V, Iurilli M, Di Cesare M, Bentham J, Phelps N, Sophiea M, Stevens G, Danaei G, Cowan M, Savin S, Riley L, Gregg E, Aekplakom W, Ahmad NA, Baker J, Chirita-Emandi A, Farzadfar F, Günther F, Heinen M, Ikeda N, Kengne AP, Khang Y-H, Laatikainen T, Laxmaiah A, Ma J, Monroy-Valle M, Padez C, Reynolds A, Soric M, Starc G, Wirth Jet al., 2023, Diminishing benefits of urban living for children and adolescents’ growth and development, Nature, Vol: 615, Pages: 874-883, ISSN: 0028-0836

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1,2,3,4,5,6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.

Journal article

Rothwell JA, Bešević J, Dimou N, Breeur M, Murphy N, Jenab M, Wedekind R, Viallon V, Ferrari P, Achaintre D, Gicquiau A, Rinaldi S, Scalbert A, Huybrechts I, Prehn C, Adamski J, Cross AJ, Keun H, Chadeau-Hyam M, Boutron-Ruault M-C, Overvad K, Dahm CC, Nøst TH, Sandanger TM, Skeie G, Zamora-Ros R, Tsilidis KK, Eichelmann F, Schulze MB, van Guelpen B, Vidman L, Sánchez M-J, Amiano P, Ardanaz E, Smith-Byrne K, Travis R, Katzke V, Kaaks R, Derksen JWG, Colorado-Yohar S, Tumino R, Bueno-de-Mesquita B, Vineis P, Palli D, Pasanisi F, Eriksen AK, Tjønneland A, Severi G, Gunter MJet al., 2023, Circulating amino acid levels and colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition and UK Biobank cohorts, BMC Medicine, Vol: 21, Pages: 1-13, ISSN: 1741-7015

BACKGROUND: Amino acid metabolism is dysregulated in colorectal cancer patients; however, it is not clear whether pre-diagnostic levels of amino acids are associated with subsequent risk of colorectal cancer. We investigated circulating levels of amino acids in relation to colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) and UK Biobank cohorts. METHODS: Concentrations of 13-21 amino acids were determined in baseline fasting plasma or serum samples in 654 incident colorectal cancer cases and 654 matched controls in EPIC. Amino acids associated with colorectal cancer risk following adjustment for the false discovery rate (FDR) were then tested for associations in the UK Biobank, for which measurements of 9 amino acids were available in 111,323 participants, of which 1221 were incident colorectal cancer cases. RESULTS: Histidine levels were inversely associated with colorectal cancer risk in EPIC (odds ratio [OR] 0.80 per standard deviation [SD], 95% confidence interval [CI] 0.69-0.92, FDR P-value=0.03) and in UK Biobank (HR 0.93 per SD, 95% CI 0.87-0.99, P-value=0.03). Glutamine levels were borderline inversely associated with colorectal cancer risk in EPIC (OR 0.85 per SD, 95% CI 0.75-0.97, FDR P-value=0.08) and similarly in UK Biobank (HR 0.95, 95% CI 0.89-1.01, P=0.09) In both cohorts, associations changed only minimally when cases diagnosed within 2 or 5 years of follow-up were excluded. CONCLUSIONS: Higher circulating levels of histidine were associated with a lower risk of colorectal cancer in two large prospective cohorts. Further research to ascertain the role of histidine metabolism and potentially that of glutamine in colorectal cancer development is warranted.

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., 2023, 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, Vol: 152, Pages: 572-599, 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., 2023, Postdiagnosis recreational physical activity and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis, International Journal of Cancer, Vol: 152, Pages: 600-615, 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

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., 2023, 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, Vol: 152, Pages: 616-634, 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., 2023, 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, Vol: 152, Pages: 635-644, 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

Cross AJ, Gunter MJ, 2023, Ultra-processed foods and colorectal neoplasia: is there a link?, JNCI-Journal of the National Cancer Institute, Vol: 115, Pages: 117-119, ISSN: 0027-8874

Journal article

Ugai T, Akimoto N, Haruki K, Harrison TA, Cao Y, Qu C, Chan AT, Campbell PT, Berndt SI, Buchanan DD, Cross AJ, Diergaarde B, Gallinger SJ, Gunter MJ, Harlid S, Hidaka A, Hoffmeister M, Brenner H, Chang-Claude J, Hsu L, Jenkins MA, Lin Y, Milne RL, Moreno V, Newcomb PA, Nishihara R, Obon-Santacana M, Pai RK, Sakoda LC, Schoen RE, Slattery ML, Sun W, Amitay EL, Alwers E, Thibodeau SN, Toland AE, Van Guelpen B, Zaidi SH, Potter JD, Meyerhardt JA, Giannakis M, Song M, Nowak JA, Peters U, Phipps AI, Ogino Set al., 2023, Prognostic role of detailed colorectal location and tumor molecular features: analyses of 13,101 colorectal cancer patients including 2994 early-onset cases, Journal of Gastroenterology, Vol: 58, Pages: 229245-229245, ISSN: 0944-1174

BACKGROUND: The pathogenic effect of colorectal tumor molecular features may be influenced by several factors, including those related to microbiota, inflammation, metabolism, and epigenetics, which may change along colorectal segments. We hypothesized that the prognostic association of colon cancer location might differ by tumor molecular characteristics. METHODS: Utilizing a consortium dataset of 13,101 colorectal cancer cases, including 2994 early-onset cases, we conducted survival analyses of detailed tumor location stratified by statuses of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF oncogenic mutation. RESULTS: There was a statistically significant trend for better colon cancer-specific survival in relation to tumor location from the cecum to sigmoid colon (Ptrend = 0.002), excluding the rectum. The prognostic association of colon location differed by MSI status (Pinteraction = 0.001). Non-MSI-high tumors exhibited the cecum-to-sigmoid trend for better colon cancer-specific survival [Ptrend < 0.001; multivariable hazard ratio (HR) for the sigmoid colon (vs. cecum), 0.80; 95% confidence interval (CI) 0.70-0.92], whereas MSI-high tumors demonstrated a suggestive cecum-to-sigmoid trend for worse survival (Ptrend = 0.020; the corresponding HR, 2.13; 95% CI 1.15-3.92). The prognostic association of colon tumor location also differed by CIMP status (Pinteraction = 0.003) but not significantly by age, stage, or other features. Furthermore, MSI-high status was a favorable prognostic indicator in all stages. CONCLUSIONS: Both detailed colonic location and tumor molecular features need to be accounted for colon cancer prognostication to advance precision medicine. Our study indicates the important role of large-scale studies to robustly examine detailed colonic subsites in molecular oncology research.

Journal article

Karavasiloglou N, Hughes DJ, Murphy N, Schomburg L, Sun Q, Seher V, Rohrmann S, Weiderpass E, Tjønneland A, Olsen A, Overvad K, Boutron-Ruault M-C, Mancini FR, Mahamat-Saleh Y, Kaaks R, Kuhn T, Schulze MB, Tumino R, Panico S, Masala G, Pala V, Sacerdote C, Derksen JWG, Skeie G, Hjartåker A, Lasheras C, Agudo A, Sánchez M-J, Chirlaque M-D, Ardanaz E, Amiano P, Van Guelpen B, Gylling B, Bradbury KE, Papier K, Freisling H, Aglago EK, Cross AJ, Riboli E, Aune D, Gunter MJ, Jenab Met al., 2023, Prediagnostic serum calcium concentrations and risk of colorectal cancer development in 2 large European prospective cohorts, The American Journal of Clinical Nutrition, Vol: 117, Pages: 33-45, ISSN: 0002-9165

BACKGROUND: Higher dietary calcium consumption is associated with lower colorectal cancer (CRC) risk. However, little data are available on the association between circulating calcium concentrations and CRC risk. OBJECTIVES: To explore the association between circulating calcium concentrations and CRC risk using data from 2 large European prospective cohort studies. METHODS: Conditional logistic regression models were used to calculate multivariable-adjusted ORs and 95% CIs in case-control studies nested within the European Prospective Investigation into Cancer and Nutrition (EPIC; n-cases = 947, n-controls = 947) and the UK Biobank (UK-BB; n-cases = 2759, n-controls = 12,021) cohorts. RESULTS: In EPIC, nonalbumin-adjusted total serum calcium (a proxy of free calcium) was not associated with CRC (OR: 0.94; 95% CI: 0.85, 1.03; modeled as continuous variable, per 1 mg/dL increase), colon cancer (OR: 0.93; 95% CI: 0.82, 1.05) or rectal cancer (OR: 1.01; 95% CI: 0.84, 1.20) risk in the multivariable adjusted model. In the UK-BB, serum ionized calcium (free calcium, most active form) was inversely associated with the risk of CRC (OR: 0.85; 95% CI: 0.76, 0.95; per 1 mg/dL) and colon cancer (OR: 0.78; 95% CI: 0.68, 0.90), but not rectal cancer (OR: 1.02; 95% CI: 0.83, 1.24) in multivariable adjusted models. Meta-analysis of EPIC and UK-BB CRC risk estimates showed an inverse risk association for CRC in the multivariable adjusted model (OR: 0.90; 95%CI: 0.84, 0.97). In analyses by quintiles, in both cohorts, higher levels of serum calcium were associated with reduced CRC risk (EPIC: ORQ5vs.Q1: 0.69; 95% CI: 0.47, 1.00; P-trend = 0.03; UK-BB: ORQ5vs.Q1: 0.82; 95% CI: 0.72, 0.94; P-trend < 0.01). Analyses by anatomical subsite showed an inverse cancer risk association in the colon (EPIC: ORQ5vs.Q1: 0.63, 95% CI: 0.39, 1.02; P-trend = 0.05; UK-BB: ORQ5vs.Q1: 0.75; 95% CI: 0.64, 0.88; P-trend < 0.01) but not the rectum. CONCLUSIONS: In UK-BB, higher serum ionized calcium

Journal article

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

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, Vol: 175, Pages: 1525-1533, ISSN: 0003-4819

Background:The effectiveness of screening for colorectal cancer (CRC) by sex and age in randomized trials is uncertain.Objective:To evaluate the 15-year effect of sigmoidoscopy screening on CRC incidence and mortality.Design:Pooled analysis of 4 large-scale randomized trials of sigmoidoscopy screening.Setting:Norway, the United States, the United Kingdom, and Italy.Participants:Women and men aged 55 to 64 years at enrollment.Intervention:Sigmoidoscopy screening.Measurements:Primary end points were cumulative incidence rate ratio (IRR) and mortality rate ratio (MRR) and rate differences after 15 years of follow-up comparing screening versus usual care in intention-to-treat analyses. Stratified analyses were done by sex, cancer site, and age at screening.Results:Analyses comprised 274 952 persons (50.7% women), 137 493 in the screening and 137 459 in the usual care group. Screening attendance was 58% to 84%. After 15 years, the rate difference for CRC incidence was 0.51 cases (95% CI, 0.40 to 0.63 cases) per 100 persons and the IRR was 0.79 (CI, 0.75 to 0.83). The rate difference for CRC mortality was 0.13 deaths (CI, 0.07 to 0.19 deaths) per 100 persons, and the MRR was 0.80 (CI, 0.72 to 0.88). Women had less benefit from screening than men for CRC incidence (IRR for women, 0.84 [CI, 0.77 to 0.91]; IRR for men, 0.75 [CI, 0.70 to 0.81]; P = 0.032 for difference) and mortality (MRR for women, 0.91 [CI, 0.77 to 1.17]; MRR for men, 0.73 [CI, 0.64 to 0.83]; P = 0.025 for difference). There was no statistically significant difference in screening effect between persons aged 55 to 59 years and those aged 60 to 64 years.Limitation:Data from the U.K. trial were less granular because of privacy regulations.Conclusion:This pooled analysis of all large randomized trials of sigmoidoscopy screening demonstrates a significant and sustained effect of sigmoidoscopy on CRC incidence and mortality for 15 years.Primary Funding Source:Health Fund of South-East Norway.

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., American Journal of Gastroenterology, Vol: 10, Pages: 1-10, ISSN: 0002-9270

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

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

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

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

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

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