Imperial College London

ProfessorElioRiboli

Faculty of MedicineSchool of Public Health

Chair in Cancer Epidemiology and Prevention
 
 
 
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Contact

 

+44 (0)20 7594 1913e.riboli Website

 
 
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Assistant

 

Ms Julieta Dourado +44 (0)20 7594 3426

 
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Location

 

152Medical SchoolSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

1128 results found

Aglago EK, Huybrechts I, Murphy N, Casagrande C, Nicolas G, Pischon T, Fedirko V, Severi G, Boutron-Ruault M-C, Fournier A, Katzke V, Kühn T, Olsen A, Tjønneland A, Dahm CC, Overvad K, Lasheras C, Agudo A, Sánchez M-J, Amiano P, Huerta JM, Ardanaz E, Perez-Cornago A, Trichopoulou A, Karakatsani A, Martimianaki G, Palli D, Pala V, Tumino R, Naccarati A, Panico S, Bueno-de-Mesquita B, May A, Derksen JWG, Hellstrand S, Ohlsson B, Wennberg M, Van Guelpen B, Skeie G, Brustad M, Weiderpass E, Cross AJ, Ward H, Riboli E, Norat T, Chajes V, Gunter MJet al., 2019, Consumption of fish and long-chain n-3 polyunsaturated fatty acids is associated with reduced risk of colorectal cancer in a large European cohort, Clinical Gastroenterology and Hepatology, ISSN: 1542-3565

BACKGROUND & AIMS: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Dietary intake of fish (total, fatty/oily, lean/white) and n-3 LC-PUFA were estimated by food frequency questionnaires given to 521,324 participants in the EPIC study; among these, 6291 individuals developed CRC (median follow up, 14.9 years). Levels of phospholipid LC-PUFA were measured by gas chromatography in plasma samples from a sub-group of 461 CRC cases and 461 matched individuals without CRC (controls). Multivariable Cox proportional hazards and conditional logistic regression models were used to calculate hazard ratios (HRs) and odds ratios (ORs), respectively, with 95% CIs. RESULTS: Total intake of fish (HR for quintile 5 vs 1, 0.88; 95% CI, 0.80-0.96; Ptrend=.005), fatty fish (HR for quintile 5 vs 1, 0.90; 95% CI, 0.82-0.98; Ptrend=.009), and lean fish (HR for quintile 5 vs 1, 0.91; 95% CI, 0.83-1.00; Ptrend=.016) were inversely associated with CRC incidence. Intake of total n-3 LC-PUFA (HR for quintile 5 vs 1, 0.86; 95% CI, 0.78-0.95; Ptrend=.010) was also associated with reduced risk of CRC, whereas dietary ratio of n-6:n-3 LC-PUFA was associated with increased risk of CRC (HR for quintile 5 vs 1, 1.31; 95% CI, 1.18-1.45; Ptrend<.001). Plasma levels of phospholipid n-3 LC-PUFA was not associated with overall CRC risk, but an inverse trend was observed for proximal compared with distal colon cancer (Pheterogeneity=.026). CONCLUSIONS: In an analysis of dietary patterns of participants in the EPIC study, we found regular consumption of fish, at recommended levels, to be associated with a lower risk of CRC, possibly through exposure to n-3 LC-PUFA.

Journal article

Laskar RS, Muller DC, Li P, Machiela MJ, Ye Y, Gaborieau V, Foll M, Hofmann JN, Colli L, Sampson JN, Wang Z, Bacq-Daian D, Boland A, Abedi-Ardekani B, Durand G, Le Calvez-Kelm F, Robinot N, Blanche H, Prokhortchouk E, Skryabin KG, Burdett L, Yeager M, Radojevic-Skodric S, Savic S, Foretova L, Holcatova I, Janout V, Mates D, Rascu S, Mukeria A, Zaridze D, Bencko V, Cybulski C, Fabianova E, Jinga V, Lissowska J, Lubinski J, Navratilova M, Rudnai P, Świątkowska B, Benhamou S, Cancel-Tassin G, Cussenot O, Trichopoulou A, Riboli E, Overvad K, Panico S, Ljungberg B, Sitaram RT, Giles GG, Milne RL, Severi G, Bruinsma F, Fletcher T, Koppova K, Larsson SC, Wolk A, Banks RE, Selby PJ, Easton DF, Pharoah P, Andreotti G, Beane Freeman LE, Koutros S, Albanes D, Männistö S, Weinstein S, Clark PE, Edwards TL, Lipworth L, Carol H, Freedman ML, Pomerantz MM, Cho E, Kraft P, Preston MA, Wilson KM, Michael Gaziano J, Sesso HD, Black A, Freedman ND, Huang W-Y, Anema JG, Kahnoski RJ, Lane BR, Noyes SL, Petillo D, Teh BT, Peters U, White E, Anderson GL, Johnson L, Luo J, Chow W-H, Moore LE, Choueiri TK, Wood C, Johansson M, McKay JD, Brown KM, Rothman N, Lathrop MG, Deleuze J-F, Wu X, Brennan P, Chanock SJ, Purdue MP, Scelo Get al., 2019, Sex specific associations in genome wide association analysis of renal cell carcinoma., Eur J Hum Genet

Renal cell carcinoma (RCC) has an undisputed genetic component and a stable 2:1 male to female sex ratio in its incidence across populations, suggesting possible sexual dimorphism in its genetic susceptibility. We conducted the first sex-specific genome-wide association analysis of RCC for men (3227 cases, 4916 controls) and women (1992 cases, 3095 controls) of European ancestry from two RCC genome-wide scans and replicated the top findings using an additional series of men (2261 cases, 5852 controls) and women (1399 cases, 1575 controls) from two independent cohorts of European origin. Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1). We also identified two additional suggestive male-specific loci at 6q24.3 (SAMD5, male odds ratio (ORmale) = 0.83 [95% CI = 0.78-0.89], Pmale = 1.71 × 10-8 compared with female odds ratio (ORfemale) = 0.98 [95% CI = 0.90-1.07], Pfemale = 0.68) and 12q23.3 (intergenic, ORmale = 0.75 [95% CI = 0.68-0.83], Pmale = 1.59 × 10-8 compared with ORfemale = 0.93 [95% CI = 0.82-1.06], Pfemale = 0.21) that attained genome-wide significance in the joint meta-analysis. Herein, we provide evidence of sex-specific associations in RCC genetic susceptibility and advocate the necessity of larger genetic and genomic studies to unravel the endogenous causes of sex bias in sexually dimorphic traits and diseases like RCC.

Journal article

Christakoudi S, Kakourou A, Markozannes G, Tzoulaki I, Weiderpass E, Brennan P, Gunter M, Dahm CC, Overvad K, Olsen A, Tjønneland A, Boutron-Ruault M-C, Madika A-L, Severi G, Katzke V, Kühn T, Bergmann MM, Boeing H, Karakatsani A, Martimianaki G, Thriskos P, Masala G, Sieri S, Panico S, Tumino R, Ricceri F, Agudo A, Redondo-Sánchez D, Colorado-Yohar SM, Mokoroa O, Melander O, Stocks T, Häggström C, Harlid S, Bueno-de-Mesquita B, van Gils CH, Vermeulen RCH, Khaw K-T, Wareham N, Tong TYN, Freisling H, Johansson M, Lennon H, Aune D, Riboli E, Trichopoulos D, Trichopoulou A, Tsilidis KKet al., Blood pressure and risk of cancer in the European prospective investigation into cancer and nutrition, International Journal of Cancer, ISSN: 0020-7136

Several studies have reported associations of hypertension with cancer, but not allresults were conclusive. We examined the association of systolic (SBP) and diastolic (DBP)blood pressure with the development of incident cancer at all anatomical sites in theEuropean Prospective Investigation into Cancer and Nutrition (EPIC). Hazard ratios (HR)(95% confidence intervals) were estimated using multivariable Cox proportional hazardsmodels, stratified by EPIC-participating centre and age at recruitment, and adjusted for sex,education, smoking, body mass index, physical activity, diabetes and dietary (in women alsoreproductive) factors. The study included 307,318 men and women, with an average followup of 13.7 (standard deviation 4.4) years and 39,298 incident cancers. We confirmed theexpected positive association with renal cell carcinoma: HR=1.12 (1.08-1.17) per 10mmHghigher SBP and HR=1.23 (1.14-1.32) for DBP. We additionally found positive associationsfor esophageal squamous cell carcinoma (SCC): HR=1.16 (1.07-1.26) (SBP), HR=1.31 (1.13-1.51) (DBP), weaker for head and neck cancers: HR=1.08 (1.04-1.12) (SBP), HR=1.09(1.01-1.17) (DBP) and, similarly, for skin SCC, colon cancer, post-menopausal breast cancerand uterine adenocarcinoma (AC), but not for esophageal AC, lung SCC, lung AC, or uterineendometroid cancer. We observed weak inverse associations of SBP with cervical SCC:HR=0.91 (0.82-1.00) and lymphomas: HR=0.97 (0.93-1.00). There were no consistentassociations with cancers in other locations.Our results are largely compatible with published studies and support weak associations ofblood pressure with cancers in specific locations and morphologies.

Journal article

Obón-Santacana M, Luján-Barroso L, Freisling H, Naudin S, Boutron-Ruault M-C, Mancini FR, Rebours V, Kühn T, Katzke V, Boeing H, Tjønneland A, Olsen A, Overvad K, Lasheras C, Rodríguez-Barranco M, Amiano P, Santiuste C, Ardanaz E, Khaw K-T, Wareham NJ, Schmidt JA, Aune D, Trichopoulou A, Thriskos P, Peppa E, Masala G, Grioni S, Tumino R, Panico S, Bueno-de-Mesquita B, Sciannameo V, Vermeulen R, Sonestedt E, Sund M, Weiderpass E, Skeie G, González CA, Riboli E, Duell EJet al., 2019, Consumption of nuts and seeds and pancreatic ductal adenocarcinoma risk in the European Prospective Investigation into Cancer and Nutrition, International Journal of Cancer, ISSN: 0020-7136

Four epidemiologic studies have assessed the association between nut intake and pancreatic cancer risk with contradictory results. The present study aims to investigate the relation between nut intake (including seeds) and pancreatic ductal adenocarcinoma (PDAC) risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards models were used to estimate hazards ratio (HR) and 95% confidence intervals (95% CI) for nut intake and PDAC risk. Information on intake of nuts was obtained from the EPIC country-specific dietary questionnaires. After a mean follow-up of 14 years, 476,160 participants were eligible for the present study and included 1,283 PDAC cases. No association was observed between consumption of nuts and PDAC risk (highest intake vs nonconsumers: HR, 0.89; 95% CI, 0.72-1.10; p-trend = 0.70). Furthermore, no evidence for effect-measure modification was observed when different subgroups were analyzed. Overall, in EPIC, the highest intake of nuts was not statistically significantly associated with PDAC risk.

Journal article

Pearson-Stuttard J, Tsilidis KK, Riboli E, Murphy Net al., Soft drinks consumption and mortality in 10 European countries: a multinational cohort study, JAMA Internal Medicine, ISSN: 2168-6114

IMPORTANCE: Soft drinks are frequently consumed but if they are associated with mortality risk in European populations is unknown.OBJECTIVE: To examine the association between total, sugar-sweetened, and artificially-sweetened soft drinks consumption and subsequent total and cause-specific mortality.DESIGN: Population based prospective cohort study.SETTING: 10 European countries.PARTICIPANTS: 451,743 men and women from the European Prospective Investigation into Cancer and Nutrition.EXPOSURE: Soft drinks consumption (total, sugar-sweetened, artificially-sweetened).MAIN OUTCOMES AND MEASURES: Total and cause-specific mortality. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using multivariable Cox proportional hazards models adjusted for other mortality risk factors.RESULTS: During a mean follow up of 16.4 years, 41,693 deaths occurred. Higher all-cause mortality was found for participants consuming ≥2 glasses/day (versus consumers of <1 glass/ month) of total soft drinks (hazard ratio [HR]=1.17; 95%CI 1.11-1.22; P-trend<.0001), sugar-sweetened soft drinks (HR=1.08; 95%CI, 1.01-1.16; P-trend=0.004), and artificially-sweetened soft drinks (HR=1.26; 95%CI, 1.16-1.35; P-trend<.0001). Positive associations were also observed for artificially-sweetened soft drinks with deaths from circulatory diseases (≥2 glasses/day versus <1 glass/ month, HR=1.52; 95%CI, 1.30-1.78; P-trend<.0001), and for sugar-sweetened soft drinks with deaths from digestive diseases (≥1 glass/day versus <1 glass/month, HR=1.59; 95%CI, 1.24-2.05; P-trend<.0001). CONCLUSION AND RELEVANCE: In this large prospective European cohort, consumption of total, sugar-sweetened, and artificially-sweetened soft drinks was positively associated with all-cause deaths. These results support public health campaigns aimed at limiting the consumption of soft drinks.

Journal article

Bixby H, Bentham J, Zhou B, Di Cesare M, Paciorek CJ, Bennett JE, Taddei C, Stevens GA, Rodriguez-Martinez A, Carrillo-Larco RM, Khang Y-H, Soric M, Gregg E, Miranda JJ, Bhutta ZA, Savin S, Sophiea MK, Iurilli MLC, Solomon BD, Cowan MJ, Riley LM, Danaei G, Bovet P, Christa-Emandi A, Hambleton IR, Hayes AJ, Ikeda N, Kengne AP, Laxmaiah A, Li Y, McGarvey ST, Mostafa A, Neovius M, Starc G, Zainuddin AA, Ezzati Met al., 2019, Rising rural body-mass index is the main driver of the global obesity epidemic, Nature, Vol: 569, Pages: 260-264, ISSN: 0028-0836

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities1,2. This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity3,4,5,6. Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55% of the global rise in mean BMI from 1985 to 2017—and more than 80% in some low- and middle-income regions—was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing—and in some countries reversal—of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories.

Journal article

Aune D, Sen A, Norat T, Riboli Eet al., 2019, Dietary fibre intake and the risk of diverticular disease: a systematic review and meta-analysis of prospective studies, European Journal of Nutrition, ISSN: 0044-264X

BACKGROUND: A high intake of dietary fibre has been associated with a reduced risk of diverticular disease in several studies; however, the dose-response relationship between fibre intake and diverticular disease risk has varied, and the available studies have not been summarised in a meta-analysis. We conducted a systematic review and meta-analysis of prospective cohort studies to clarify the association between dietary fibre intake, fibre subtypes, and the risk of diverticular disease. METHODS: PubMed and Embase databases were searched up to August 9th 2018. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random-effects model and nonlinear associations were modelled using fractional polynomial models. RESULTS: Five prospective cohort studies with 19,282 cases and 865,829 participants were included in the analysis of dietary fibre and diverticular disease risk. The summary RR was 0.74 (95% CI 0.71-0.78, I2 = 0%) per 10 g/day. There was no evidence of a nonlinear association between dietary fibre intake and diverticular disease risk, pnonlinearity = 0.35, and there was a 23%, 41% and 58% reduction in risk for an intake of 20, 30, and 40 g/day, respectively, compared to 7.5 g/day. There was no evidence of publication bias with Egger's test, p = 0.58 and the association persisted in subgroup and sensitivity analyses. The summary RR per 10 g/day was 0.74 (95% CI 0.67-0.81, I2 = 60%, n = 4) for cereal fibre, 0.56 (95% CI 0.37-0.84, I2 = 73%, n = 2) for fruit fibre, and 0.80 (95% CI 0.45-1.44, I2 = 87%, n = 2) for vegetable fibre. CONCLUSIONS: These results suggest that a high fibre intake may reduce the risk of diverticular disease and individuals consuming 30 g of fibre per day have a 41% reduction in risk compared to persons with a low fibre intake. Further studies are needed on f

Journal article

Key TJ, Appleby PN, Bradbury KE, Sweeting M, Wood A, Johansson I, Kühn T, Steur M, Weiderpass E, Wennberg M, Würtz AML, Agudo A, Andersson J, Arriola L, Boeing H, Boer JMA, Bonnet F, Boutron-Ruault M-C, Cross AJ, Ericson U, Fagherazzi G, Ferrari P, Gunter M, Huerta JM, Katzke V, Khaw K-T, Krogh V, La Vecchia C, Matullo G, Moreno-Iribas C, Naska A, Nilsson LM, Olsen A, Overvad K, Palli D, Panico S, Molina-Portillo E, Quirós JR, Skeie G, Sluijs I, Sonestedt E, Stepien M, Tjønneland A, Trichopoulou A, Tumino R, Tzoulaki I, van der Schouw YT, Verschuren WMM, Di Angelantonio E, Langenberg C, Forouhi N, Wareham N, Butterworth A, Riboli E, Danesh Jet al., 2019, Consumption of meat, fish, dairy products, eggs and risk of ischemic heart disease: A prospective study of 7198 incident cases among 409,885 participants in the pan-European EPIC cohort, Circulation, ISSN: 0009-7322

BACKGROUND: There is uncertainty about the relevance of animal foods to the etiology of ischemic heart disease (IHD). We examined meat, fish, dairy products and eggs and risk for IHD in the pan-European EPIC cohort. METHODS: A prospective study of 409,885 men and women in nine European countries. Diet was assessed using validated questionnaires, calibrated using 24-hour recalls. Lipids and blood pressure were measured in a subsample. During 12.6 years mean follow up, 7198 participants had a myocardial infarction or died from IHD. The relationships of animal foods with risk were examined using Cox regression with adjustment for other animal foods and relevant covariates. RESULTS: The hazard ratio (HR) for IHD was 1.19 (95% CI 1.06-1.33) for a 100 g/d increment in intake of red and processed meat, and this remained significant after excluding the first 4 years of follow-up (HR 1.25 [1.09-1.42]). Risk was inversely associated with intakes of yogurt (HR 0.93 [0.89-0.98] per 100 g/d increment), cheese (HR 0.92 [0.86-0.98] per 30 g/d increment) and eggs (HR 0.93 [0.88-0.99] per 20 g/d increment); the associations with yogurt and eggs were attenuated and non-significant after excluding the first 4 years of follow-up. Risk was not significantly associated with intakes of poultry, fish or milk. In analyses modelling dietary substitutions, replacement of 100 kcal/d from red and processed meat with 100 kcal/d from fatty fish, yogurt, cheese or eggs was associated with approximately 20% lower risk of IHD. Consumption of red and processed meat was positively associated with serum non-HDL cholesterol concentration and systolic blood pressure, and consumption of cheese was inversely associated with serum non-HDL cholesterol. CONCLUSIONS: Risk for IHD was positively associated with consumption of red and processed meat, and inversely associated with consumption of yogurt, cheese and eggs, although the associations with yogurt and eggs may be influenced by reverse causation bias. It

Journal article

Assi N, Rinaldi S, Viallon V, Dashti SG, Dossus L, Fournier A, Cervenka I, Kvaskoff M, Turzanski-Fortner R, Bergmann M, Boeing H, Panico S, Ricceri F, Palli D, Tumino R, Grioni S, Sánchez Pérez MJ, Chirlaque M-D, Bonet C, Gurrea AB, Amiano Etxezarreta P, Merino S, Bueno de Mesquita HB, van Gils CH, Onland-Moret C, Tjønneland A, Overvad K, Trichopoulou A, Martimianaki G, Karakatsani A, Key T, Christakoudi S, Ellingjord-Dale M, Tsilidis K, Riboli E, Kaaks R, Gunter MJ, Ferrari Pet al., 2019, Mediation analysis of the alcohol-postmenopausal breast cancer relationship by sex hormones in the EPIC cohort, International Journal of Cancer, ISSN: 0020-7136

Alcohol consumption is associated with higher risk of breast cancer (BC); however, the biological mechanisms underlying this association are not fully elucidated, particularly the extent to which this relationship is mediated by sex hormone levels. Circulating concentrations of estradiol, testosterone, their free fractions and sex-hormone binding globulin (SHBG), were examined in 430 incident BC cases and 645 matched controls among alcohol-consuming postmenopausal women nested within the European Prospective Investigation into Cancer and Nutrition. Mediation analysis was applied to assess whether individual hormone levels mediated the relationship between alcohol intake and BC risk. An alcohol-related hormonal signature, obtained by partial least square (PLS) regression, was evaluated as a potential mediator. Total (TE), natural direct and natural indirect effects (NIE) were estimated. Alcohol intake was positively associated with overall BC risk and specifically with estrogen receptor-positive tumors with respectively TE = 1.17(95%CI: 1.01,1.35) and 1.36(1.08,1.70) for a 1-standard deviation (1-SD) increase of intake. There was no evidence of mediation by sex steroids or SHBG separately except for a weak indirect effect through free estradiol where NIE = 1.03(1.00,1.06). However, an alcohol-related hormonal signature negatively associated with SHBG and positively with estradiol and testosterone was associated with BC risk (odds ratio [OR] = 1.25 [1.07,1.47]) for a 1-SD higher PLS score, and had a statistically significant NIE accounting for a mediated proportion of 24%. There was limited evidence of mediation of the alcohol-BC association by individual sex hormones. However, a hormonal signature, reflecting lower levels of SHBG and higher levels of sex steroids, mediated a substantial proportion of the association.

Journal article

Smith Byrne K, Appleby PN, Key TJ, Holmes MV, Fensom GK, Agudo A, Ardanaz E, Boeing H, Bueno-de-Mesquita HB, Chirlaque MD, Kaaks R, Larrañaga N, Palli D, Perez-Cornago A, Quirós JR, Ricceri F, Sánchez MJ, Tagliabue G, Tsilidis KK, Tumino R, Fortner RT, Ferrari P, PRACTICAL Consortium, Riboli E, Lilja H, Travis RCet al., 2019, The role of plasma microseminoprotein-beta in prostate cancer: an observational nested case-control and Mendelian randomization study in the European prospective investigation into cancer and nutrition., Ann Oncol

BACKGROUND: Microseminoprotein-beta (MSP), a protein secreted by the prostate epithelium, may have a protective role in the development of prostate cancer. The only previous prospective study found a 2% reduced prostate cancer risk per unit increase in MSP. This work investigates the association of MSP with prostate cancer risk using observational and Mendelian randomization (MR) methods. PATIENTS AND METHODS: A nested case-control study was conducted with the European Prospective Investigation into Cancer and Nutrition (EPIC) with 1871 cases and 1871 matched controls. Conditional logistic regression analysis was used to investigate the association of pre-diagnostic circulating MSP with risk of incident prostate cancer overall and by tumour subtype. EPIC-derived estimates were combined with published data to calculate an MR estimate using two-sample inverse-variance method. RESULTS: Plasma MSP concentrations were inversely associated with prostate cancer risk after adjusting for total prostate-specific antigen concentration [odds ratio (OR) highest versus lowest fourth of MSP = 0.65, 95% confidence interval (CI) 0.51-0.84, Ptrend = 0.001]. No heterogeneity in this association was observed by tumour stage or histological grade. Plasma MSP concentrations were 66% lower in rs10993994 TT compared with CC homozygotes (per allele difference in MSP: 6.09 ng/ml, 95% CI 5.56-6.61, r2=0.42). MR analyses supported a potentially causal protective association of MSP with prostate cancer risk (OR per 1 ng/ml increase in MSP for MR: 0.96, 95% CI 0.95-0.97 versus EPIC observational: 0.98, 95% CI 0.97-0.99). Limitations include lack of complete tumour subtype information and more complete information on the biological function of MSP. CONCLUSIONS: In this large prospective European study and using MR analyses, men with high circulating MSP concentration have a lower risk of prostate cancer. MSP may play a causally protective role in prostate c

Journal article

Schmidt JA, Fensom GK, Rinaldi S, Scalbert A, Appleby PN, Achaintre D, Gicquiau A, Gunter MJ, Ferrari P, Kaaks R, Kühn T, Boeing H, Trichopoulou A, Karakatsani A, Peppa E, Palli D, Sieri S, Tumino R, Bueno-de-Mesquita B, Agudo A, Sánchez M-J, Chirlaque M-D, Ardanaz E, Larrañaga N, Perez-Cornago A, Assi N, Riboli E, Tsilidis KK, Key TJ, Travis RCet al., 2019, Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case-control sets from EPIC, International Journal of Cancer, ISSN: 0020-7136

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case-control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR1SD ) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR1SD  = 0.77, 95% confidence interval 0.66-0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR1SD  = 0.72, 0.57-0.90), or lysophosphatidylcholines (OR1SD  = 0.81, 0.69-0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR1SD  = 0.77, 0.61-0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.

Journal article

Sasamoto N, Babic A, Rosner BA, Fortner RT, Vitonis AF, Yamamoto H, Fichorova RN, Tjønneland A, Hansen L, Overvad K, Kvaskoff M, Fournier A, Mancini FR, Boeing H, Trichopoulou A, Peppa E, Karakatsani A, Palli D, Pala V, Mattiello A, Tumino R, Grasso C, Onland-Moret NC, Weiderpass E, Quirós JR, Lujan-Barroso L, Rodríguez-Barranco M, Colorado-Yohar S, Barricarte A, Dorronsoro M, Idahl A, Lundin E, Sartor H, Khaw K-T, Key TJ, Muller D, Riboli E, Gunter M, Dossus L, Kaaks R, Cramer DW, Tworoger SS, Terry KLet al., Predicting circulating CA125 levels among healthy premenopausal women, Cancer Epidemiology, Biomarkers and Prevention, ISSN: 1055-9965

Background: CA125 is the most promising ovarian cancer screening biomarker to date. Multiple studies reported CA125 levels vary by personal characteristics, which could inform personalized CA125 thresholds. However, this has not been well described in premenopausal women. Methods: We evaluated predictors of CA125 levels among 815 premenopausal women from the New England Case Control Study (NEC). We developed linear and dichotomous (≥ 35 U/ mL) CA125 prediction models and externally validated an abridged model restricting to available predictors among 473 premenopausal women in the European Prospective Investigation into Cancer and Nutrition Study (EPIC).Results: The final linear CA125 prediction model included age, race, tubal ligation, endometriosis, menstrual phase at blood draw, and fibroids, which explained 7% of the total variance of CA125. The correlation between observed and predicted CA125 levels based on the abridged model (including age, race, and menstrual phase at blood draw) had similar correlation coefficients in NEC(r=0.22) and in EPIC(r=0.22). The dichotomous CA125 prediction model included age, tubal ligation, endometriosis, prior personal cancer diagnosis, family history of ovarian cancer, number of miscarriages, menstrual phase at blood draw and smoking status with AUC of 0.83. The abridged dichotomous model (including age, number of miscarriages, menstrual phase at blood draw, and smoking status) showed similar AUCs in NEC(0.73) and in EPIC(0.78).Conclusions: We identified a combination of factors associated with CA125 levels in premenopausal women.Impact: Our model could be valuable in identifying healthy women likely to have elevated CA125 and consequently improve its specificity for ovarian cancer screening.

Journal article

Perrier F, Viallon V, Ambatipudi S, Ghantous A, Cuenin C, Hernandez-Vargas H, Chajès V, Baglietto L, Matejcic M, Moreno-Macias H, Kühn T, Boeing H, Karakatsani A, Kotanidou A, Trichopoulou A, Sieri S, Panico S, Fasanelli F, Dolle M, Onland-Moret C, Sluijs I, Weiderpass E, Quirós JR, Agudo A, Huerta JM, Ardanaz E, Dorronsoro M, Tong TYN, Tsilidis K, Riboli E, Gunter MJ, Herceg Z, Ferrari P, Romieu Iet al., 2019, Association of leukocyte DNA methylation changes with dietary folate and alcohol intake in the EPIC study, Clinical Epigenetics, Vol: 11, ISSN: 1868-7083

BACKGROUND: There is increasing evidence that folate, an important component of one-carbon metabolism, modulates the epigenome. Alcohol, which can disrupt folate absorption, is also known to affect the epigenome. We investigated the association of dietary folate and alcohol intake on leukocyte DNA methylation levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Leukocyte genome-wide DNA methylation profiles on approximately 450,000 CpG sites were acquired with Illumina HumanMethylation 450K BeadChip measured among 450 women control participants of a case-control study on breast cancer nested within the EPIC cohort. After data preprocessing using surrogate variable analysis to reduce systematic variation, associations of DNA methylation with dietary folate and alcohol intake, assessed with dietary questionnaires, were investigated using CpG site-specific linear models. Specific regions of the methylome were explored using differentially methylated region (DMR) analysis and fused lasso (FL) regressions. The DMR analysis combined results from the feature-specific analysis for a specific chromosome and using distances between features as weights whereas FL regression combined two penalties to encourage sparsity of single features and the difference between two consecutive features. RESULTS: After correction for multiple testing, intake of dietary folate was not associated with methylation level at any DNA methylation site, while weak associations were observed between alcohol intake and methylation level at CpG sites cg03199996 and cg07382687, with qval = 0.029 and qval = 0.048, respectively. Interestingly, the DMR analysis revealed a total of 24 and 90 regions associated with dietary folate and alcohol, respectively. For alcohol intake, 6 of the 15 most significant DMRs were identified through FL. CONCLUSIONS: Alcohol intake was associated with methylation levels at two CpG sites. Evidence from DMR and FL analyses

Journal article

Fedirko V, Jenab M, Meplan C, Jones JS, Zhu W, Schomburg L, Siddiq A, Hybsier S, Overvad K, Tjonneland A, Omichessan H, Perduca V, Boutron-Ruault M-C, Kuehn T, Katzke V, Aleksandrova K, Trichopoulou A, Karakatsani A, Kotanidou A, Tumino R, Panico S, Masala G, Agnoli C, Naccarati A, Bueno-de-Mesquita B, Vermeulen RCH, Weiderpass E, Skeie G, Nost TH, Lujan-Barroso L, Ramon Quiros J, Maria Huerta J, Rodriguez-Barranco M, Barricarte A, Gylling B, Harlid S, Bradbury KE, Wareham N, Khaw K-T, Gunter M, Murphy N, Freisling H, Tsilidis K, Aune D, Riboli E, Hesketh JE, Hughes DJet al., 2019, Association of Selenoprotein and Selenium Pathway Genotypes with Risk of Colorectal Cancer and Interaction with Selenium Status, 4th International Conference on Selenium in the Environment and Human Health, Publisher: MDPI, Pages: 53-54, ISSN: 2072-6643

Conference paper

Bien SA, Su Y-R, Conti DV, Harrison TA, Qu C, Guo X, Lu Y, Albanes D, Auer PL, Banbury BL, Berndt SI, Bézieau S, Brenner H, Buchanan DD, Caan BJ, Campbell PT, Carlson CS, Chan AT, Chang-Claude J, Chen S, Connolly CM, Easton DF, Feskens EJM, Gallinger S, Giles GG, Gunter MJ, Hampe J, Huyghe JR, Hoffmeister M, Hudson TJ, Jacobs EJ, Jenkins MA, Kampman E, Kang HM, Kühn T, Küry S, Lejbkowicz F, Le Marchand L, Milne RL, Li L, Li CI, Lindblom A, Lindor NM, Martín V, McNeil CE, Melas M, Moreno V, Newcomb PA, Offit K, Pharaoh PDP, Potter JD, Qu C, Riboli E, Rennert G, Sala N, Schafmayer C, Scacheri PC, Schmit SL, Severi G, Slattery ML, Smith JD, Trichopoulou A, Tumino R, Ulrich CM, van Duijnhoven FJB, Van Guelpen B, Weinstein SJ, White E, Wolk A, Woods MO, Wu AH, Abecasis GR, Casey G, Nickerson DA, Gruber SB, Hsu L, Zheng W, Peters Uet al., 2019, Genetic variant predictors of gene expression provide new insight into risk of colorectal cancer, Human Genetics, Vol: 138, Pages: 307-326, ISSN: 0340-6717

Genome-wide association studies have reported 56 independently associated colorectal cancer (CRC) risk variants, most of which are non-coding and believed to exert their effects by modulating gene expression. The computational method PrediXcan uses cis-regulatory variant predictors to impute expression and perform gene-level association tests in GWAS without directly measured transcriptomes. In this study, we used reference datasets from colon (n = 169) and whole blood (n = 922) transcriptomes to test CRC association with genetically determined expression levels in a genome-wide analysis of 12,186 cases and 14,718 controls. Three novel associations were discovered from colon transverse models at FDR ≤ 0.2 and further evaluated in an independent replication including 32,825 cases and 39,933 controls. After adjusting for multiple comparisons, we found statistically significant associations using colon transcriptome models with TRIM4 (discovery P = 2.2 × 10- 4, replication P = 0.01), and PYGL (discovery P = 2.3 × 10- 4, replication P = 6.7 × 10- 4). Interestingly, both genes encode proteins that influence redox homeostasis and are related to cellular metabolic reprogramming in tumors, implicating a novel CRC pathway linked to cell growth and proliferation. Defining CRC risk regions as one megabase up- and downstream of one of the 56 independent risk variants, we defined 44 non-overlapping CRC-risk regions. Among these risk regions, we identified genes associated with CRC (P < 0.05) in 34/44 CRC-risk regions. Importantly, CRC association was found for two genes in the previously reported 2q25 locus, CXCR1 and CXCR2, which are potential cancer therapeutic targets. These findings provide strong candidate genes to prioritize for subsequent laboratory follow-up of GWAS loci. Thi

Journal article

Solans M, Benavente Y, Saez M, Agudo A, Jakszyn P, Naudin S, Hosnijeh FS, Gunter M, Huybrechts I, Ferrari P, Besson C, Mahamat-Saleh Y, Boutron-Ruault M-C, Kühn T, Kaaks R, Boeing H, Lasheras C, Sánchez M-J, Amiano P, Chirlaque MD, Ardanaz E, Schmidt JA, Vineis P, Riboli E, Trichopoulou A, Karakatsani A, Valanou E, Masala G, Agnoli C, Tumino R, Sacerdote C, Mattiello A, Skeie G, Weiderpass E, Jerkeman M, Dias JA, Späth F, Nilsson LM, Dahm CC, Overvad K, Petersen KEN, Tjønneland A, de Sanjose S, Vermeulen R, Nieters A, Casabonne Det al., 2019, Inflammatory potential of diet and risk of lymphoma in the European Prospective Investigation into Cancer and Nutrition, European Journal of Nutrition, ISSN: 0044-264X

INTRODUCTION: Chronic inflammation plays a critical role in lymphomagenesis and several dietary factors seem to be involved its regulation. The aim of the current study was to assess the association between the inflammatory potential of the diet and the risk of lymphoma and its subtypes in the European Investigation into Cancer and Nutrition (EPIC) study. METHODS: The analysis included 476,160 subjects with an average follow-up of 13.9 years, during which 3,136 lymphomas (135 Hodgkin lymphoma (HL), 2606 non-Hodgkin lymphoma (NHL) and 395 NOS) were identified. The dietary inflammatory potential was assessed by means of an inflammatory score of the diet (ISD), calculated using 28 dietary components and their corresponding inflammatory weights. The association between the ISD and lymphoma risk was estimated by hazard ratios (HR) and 95% confidence intervals (CI) calculated by multivariable Cox regression models adjusted for potential confounders. RESULTS: The ISD was not associated with overall lymphoma risk. Among lymphoma subtypes, a positive association between the ISD and mature B-cell NHL (HR for a 1-SD increase: 1.07 (95% CI 1.01; 1.14), p trend = 0.03) was observed. No statistically significant association was found among other subtypes. However, albeit with smaller number of cases, a suggestive association was observed for HL (HR for a 1-SD increase = 1.22 (95% CI 0.94; 1.57), p trend 0.13). CONCLUSIONS: Our findings suggested that a high ISD score, reflecting a pro-inflammatory diet, was modestly positively associated with the risk of B-cell lymphoma subtypes. Further large prospective studies on low-grade inflammation induced by diet are warranted to confirm these findings.

Journal article

Perez-Cornago A, Huybrechts I, Appleby PN, Schmidt JA, Crowe FL, Overvad K, Tjønneland A, Kühn T, Katzke V, Trichopoulou A, Karakatsani A, Peppa E, Grioni S, Palli D, Sacerdote C, Tumino R, Bueno-de-Mesquita HB, Larrañaga N, Sánchez M-J, Quirós JR, Ardanaz E, Chirlaque M-D, Agudo A, Bjartell A, Wallström P, Chajes V, Tsilidis KK, Aune D, Riboli E, Travis RC, Key TJet al., 2019, Intake of individual fatty acids and risk of prostate cancer in the European prospective investigation into cancer and nutrition, International Journal of Cancer, ISSN: 0020-7136

The associations of individual dietary fatty acids with prostate cancer risk have not been examined comprehensively. We examined the prospective association of individual dietary fatty acids with prostate cancer risk overall, by tumor subtypes, and prostate cancer death. 142,239 men from the European Prospective Investigation into Cancer and Nutrition who were free from cancer at recruitment were included. Dietary intakes of individual fatty acids were estimated using center-specific validated dietary questionnaires at baseline and calibrated with 24-hour recalls. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average follow-up of 13.9 years, 7,036 prostate cancer cases and 936 prostate cancer deaths were ascertained. Intakes of individual fatty acids were not related to overall prostate cancer risk. There was evidence of heterogeneity in the association of some short chain saturated fatty acids with prostate cancer risk by tumor stage (Pheterogeneity <0.015), with a positive association with risk of advanced stage disease for butyric acid (4:0; HR1SD =1.08; 95%CI=1.01-1.15; P-trend=0.026). There were no associations with fatal prostate cancer, with the exception of a slightly higher risk for those who consumed more eicosenoic acid (22:1n-9c; HR1SD =1.05; 1.00-1.11; P-trend=0.048) and eicosapentaenoic acid (20:5n-3c; HR1SD =1.07; 1.00-1.14; P-trend=0.045). There was no evidence that dietary intakes of individual fatty acids were associated with overall prostate cancer risk. However, a higher intake of butyric acid might be associated with a higher risk of advanced, whereas intakes of eicosenoic and eicosapentaenoic acids might be positively associated with fatal prostate cancer risk. This article is protected by copyright. All rights reserved.

Journal article

Vissers LET, Sluijs I, van der Schouw YT, Forouhi NG, Imamura F, Burgess S, Barricarte A, Boeing H, Bonet C, Chirlaque M-D, Fagherazzi G, Franks PW, Freisling H, Gunter MJ, Quirós JR, Ibsen DB, Kaaks R, Key T, Khaw KT, Kühn T, Mokoroa O, Nilsson PM, Overvad K, Pala V, Palli D, Panico S, Sacerdote C, Spijkerman AMW, Tjonneland A, Tumino R, Rodríguez-Barranco M, Rolandsson O, Riboli E, Sharp SJ, Langenberg C, Wareham NJet al., 2019, Dairy product intake and risk of type 2 diabetes in EPIC-InterAct: a mendelian randomization study, Diabetes Care, Vol: 42, ISSN: 0149-5992

OBJECTIVE To estimate the causal association between intake of dairy products and incident type 2 diabetes.RESEARCH DESIGN AND METHODS The analysis included 21,820 European individuals (9,686 diabetes cases) of the EPIC-InterAct case-cohort study. Participants were genotyped, and rs4988235 (LCT-12910C>T), a SNP for lactase persistence (LP) which enables digestion of dairy sugar, i.e., lactose, was imputed. Baseline dietary intakes were assessed with diet questionnaires. We investigated the associations between imputed SNP dosage for rs4988235 and intake of dairy products and other foods through linear regression. Mendelian randomization (MR) estimates for the milk-diabetes relationship were obtained through a two-stage least squares regression.RESULTS Each additional LP allele was associated with a higher intake of milk (β 17.1 g/day, 95% CI 10.6–23.6) and milk beverages (β 2.8 g/day, 95% CI 1.0–4.5) but not with intake of other dairy products. Other dietary intakes associated with rs4988235 included fruits (β −7.0 g/day, 95% CI −12.4 to −1.7 per additional LP allele), nonalcoholic beverages (β −18.0 g/day, 95% CI −34.4 to −1.6), and wine (β −4.8 g/day, 95% CI −9.1 to −0.6). In instrumental variable analysis, LP-associated milk intake was not associated with diabetes (hazard ratio 0.99per 15 g/day, 95% CI 0.93–1.05).CONCLUSIONS rs4988235 was associated with milk intake but not with intake of other dairy products. This MR study does not suggest that milk intake is associated with diabetes, which is consistent with previous observational and genetic associations. LP may be associated with intake of other foods as well, but owing to the modest associations we consider it unlikely that this has caused the observed null result.

Journal article

Dam V, van der Schouw YT, Onland-Moret NC, Groenwold RHH, Peters SAE, Burgess S, Wood AM, Chirlaque M-D, Moons KGM, Oliver-Williams C, Schuit E, Tikk K, Weiderpass E, Holm M, Tjønneland A, Kühn T, Fortner RT, Trichopoulou A, Karakatsani A, La Vecchia C, Ferrari P, Gunter M, Masala G, Sieri S, Tumino R, Panico S, Boer JMA, Verschuren WMM, Salamanca-Fernández E, Arriola L, Moreno-Iribas C, Engström G, Melander O, Nordendahl M, Wennberg P, Key TJ, Colorado-Yohar S, Matullo G, Overvad K, Clavel-Chapelon F, Boeing H, Quiros JR, di Angelantonio E, Langenberg C, Sweeting MJ, Riboli E, Wareham NJ, Danesh J, Butterworth Aet al., 2019, Association of menopausal characteristics and risk of coronary heart disease: a pan-European case-cohort analysis., Int J Epidemiol

BACKGROUND: Earlier age at menopause has been associated with increased risk of coronary heart disease (CHD), but the shape of association and role of established cardiovascular risk factors remain unclear. Therefore, we examined the associations between menopausal characteristics and CHD risk; the shape of the association between age at menopause and CHD risk; and the extent to which these associations are explained by established cardiovascular risk factors. METHODS: We used data from EPIC-CVD, a case-cohort study, which includes data from 23 centres from 10 European countries. We included only women, of whom 10 880 comprise the randomly selected sub-cohort, supplemented with 4522 cases outside the sub-cohort. We conducted Prentice-weighted Cox proportional hazards regressions with age as the underlying time scale, stratified by country and adjusted for relevant confounders. RESULTS: After confounder and intermediate adjustment, post-menopausal women were not at higher CHD risk compared with pre-menopausal women. Among post-menopausal women, earlier menopause was linearly associated with higher CHD risk [HRconfounder and intermediate adjusted per-year decrease = 1.02, 95% confidence interval (CI) = 1.01-1.03, p = 0.001]. Women with a surgical menopause were at higher risk of CHD compared with those with natural menopause (HRconfounder-adjusted = 1.25, 95% CI = 1.10-1.42, p < 0.001), but this attenuated after additional adjustment for age at menopause and intermediates (HR = 1.12, 95% CI = 0.96-1.29, p = 0.15). A proportion of the association was explained by cardiovascular risk factors. CONCLUSIONS: Earlier and surgical menopause were associated with higher CHD risk. These associations could partially be explained by differences in conventional cardiovascular risk factors. These women might benefit from close monitoring of cardiovas

Journal article

Riso L, Kaaks R, Kühn T, Sookthai D, Forsgren L, Trupp M, Trichopoulou A, La Vecchia C, Karakatsani A, Gavrila D, Ferrari P, Freisling H, Petersson J, Lewan S, Vermeulen RC, Panico S, Masala G, Ardanaz E, Krogh V, Perneczky RG, Middleton LT, Mokoroa O, Sacerdote C, Sieri S, Hayat SA, Brayne C, Riboli E, Vineis P, Gallo V, Katzke VAet al., 2019, General and abdominal adiposity and the risk of parkinson's disease.A prospective chort study, Parkinsonism and Related Disorders, ISSN: 1353-8020

IntroductionDue to demographic change, an increase in the frequency of Parkinson's disease (PD) patients is expected in the future and, thus, the identification of modifiable risk factors is urgently needed. We aimed to examine the associations of body mass index (BMI) and waist circumference (WC) with incident PD.MethodsIn 13 of the 23 centers of the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a total of 734 incident cases of PD were identified between 1992 and 2012 with a mean follow-up of 12 years. Cox proportional hazards regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI). We modelled anthropometric variables as continuous and categorical exposures and performed subgroup analyses by potential effect modifiers including sex and smoking.ResultsWe found no association between BMI, WC and incident PD, neither among men nor among women. Among never and former smokers, BMI and waist circumference were also not associated with PD risk. For male smokers, however, we observed a statistically significant inverse association between BMI and PD risk (HR 0.51, 95%CI: 0.30, 0.84) and the opposite for women, i.e. a significant direct association of BMI (HR 1.79, 95%CI: 1.04, 3.08) and waist circumference (HR 1.64, 95%CI: 1.03, 2.61) with risk of PD.ConclusionOur data revealed no association between excess weight and PD risk but a possible interaction between anthropometry, sex and smoking.

Journal article

Gunter MJ, Alhomoud S, Arnold M, Brenner H, Burn J, Casey G, Chan AT, Cross AJ, Giovannucci E, Hoover R, Houlston R, Jenkins M, Laurent-Puig P, Peters U, Ransohoff D, Riboli E, Sinha R, Stadler ZK, Brennan P, Chanock SJet al., 2019, Meeting Report from the joint IARC-NCI international cancer seminar series: a focus on colorectal cancer, Annals of Oncology, ISSN: 0923-7534

Despite significant progress in our understanding of the etiology, biology and genetics of colorectal cancer, as well as important clinical advances, it remains the third most frequently diagnosed cancer worldwide and is the second leading cause of cancer death. Based on demographic projections, the global burden of colorectal cancer would be expected to rise by 72% from 1.8 million new cases in 2018 to over 3 million in 2040 with substantial increases anticipated in low and middle income countries. In this meeting report, we summarize the content of a joint workshop led by the National Cancer Institute (NCI) and the International Agency for Research on Cancer (IARC) which was held to summarize the important achievements that have been made in our understanding of colorectal cancer etiology, genetics, early detection and treatment and to identify key research questions that remain to be addressed.

Journal article

Costas L, Lujan-Barroso L, Benavente Y, Allen NE, Amiano P, Ardanaz E, Besson C, Boeing H, Bueno-de-Mesquita B, Cervenka I, Fortner RT, Fournier A, Gunter M, Harlid S, Huerta JM, Jerkeman M, Jirström K, Kaaks R, Karakatsani A, Khaw K-T, Kotanidou A, Lund E, Masala G, Mattiello A, Melin B, Menéndez V, Murphy N, Nieters A, Overvad K, Riboli E, Sacerdote C, Sánchez M-J, Schmidt JA, Sieri S, Tjønneland A, Trichopoulou A, Tumino R, Vermeulen R, Weiderpass E, de Sanjosé S, Agudo A, Casabonne Det al., 2019, Reproductive factors, exogenous hormone use, and risk of B-cell non-Hodgkin lymphoma in a cohort of women from the European prospective investigation into cancer and nutrition, American Journal of Epidemiology, Vol: 188, Pages: 274-281, ISSN: 1476-6256

The role of hormonal factors in the etiology of lymphoid neoplasms remains unclear. Previous studies have yielded conflicting results, have lacked sufficient statistical power to assess many lymphoma subtypes, or have lacked detailed information on relevant exposures. Within the European Prospective Investigation Into Cancer and Nutrition cohort, we analyzed comprehensive data on reproductive factors and exogenous hormone use collected at baseline (1992-2000) among 343,458 women, including data on 1,427 incident cases of B-cell non-Hodgkin lymphoma (NHL) and its major subtypes identified after a mean follow-up period of 14 years (through 2015). We estimated hazard ratios and 95% confidence intervals using multivariable proportional hazards modeling. Overall, we observed no statistically significant associations between parity, age at first birth, breastfeeding, oral contraceptive use, or ever use of postmenopausal hormone therapy and risk of B-cell NHL or its subtypes. Women who had undergone surgical menopause had a 51% higher risk of B-cell NHL (based on 67 cases) than women with natural menopause (hazard ratio = 1.51, 95% confidence interval: 1.17, 1.94). Given that this result may have been due to chance, our results provide little support for the hypothesis that sex hormones play a role in lymphomagenesis.

Journal article

Gasull M, Pumarega J, Kiviranta H, Rantakokko P, Raaschou-Nielsen O, Bergdahl IA, Sandanger TM, Goñi F, Cirera L, Donat-Vargas C, Alguacil J, Iglesias M, Tjønneland A, Overvad K, Mancini FR, Boutron-Ruault M-C, Severi G, Johnson T, Kühn T, Trichopoulou A, Karakatsani A, Peppa E, Palli D, Pala V, Tumino R, Naccarati A, Panico S, Verschuren M, Vermeulen R, Rylander C, Nøst TH, Rodríguez-Barranco M, Molinuevo A, Chirlaque M-D, Ardanaz E, Sund M, Key T, Ye W, Jenab M, Michaud D, Matullo G, Canzian F, Kaaks R, Nieters A, Nöthlings U, Jeurnink S, Chajes V, Matejcic M, Gunter M, Aune D, Riboli E, Agudo A, Gonzalez CA, Weiderpass E, Bueno-de-Mesquita B, Duell EJ, Vineis P, Porta Met al., 2019, Methodological issues in a prospective study on plasma concentrations of persistent organic pollutants and pancreatic cancer risk within the EPIC cohort, Environmental Research, Vol: 169, Pages: 417-433, ISSN: 0013-9351

BACKGROUND: The use of biomarkers of environmental exposure to explore new risk factors for pancreatic cancer presents clinical, logistic, and methodological challenges that are also relevant in research on other complex diseases. OBJECTIVES: First, to summarize the main design features of a prospective case-control study -nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort- on plasma concentrations of persistent organic pollutants (POPs) and pancreatic cancer risk. And second, to assess the main methodological challenges posed by associations among characteristics and habits of study participants, fasting status, time from blood draw to cancer diagnosis, disease progression bias, basis of cancer diagnosis, and plasma concentrations of lipids and POPs. Results from etiologic analyses on POPs and pancreatic cancer risk, and other analyses, will be reported in future articles. METHODS: Study subjects were 1533 participants (513 cases and 1020 controls matched by study centre, sex, age at blood collection, date and time of blood collection, and fasting status) enrolled between 1992 and 2000. Plasma concentrations of 22 POPs were measured by gas chromatography - triple quadrupole mass spectrometry (GC-MS/MS). To estimate the magnitude of the associations we calculated multivariate-adjusted odds ratios by unconditional logistic regression, and adjusted geometric means by General Linear Regression Models. RESULTS: There were differences among countries in subjects' characteristics (as age, gender, smoking, lipid and POP concentrations), and in study characteristics (as time from blood collection to index date, year of last follow-up, length of follow-up, basis of cancer diagnosis, and fasting status). Adjusting for centre and time of blood collection, no factors were significantly associated with fasting status. Plasma concentrations of lipids were related to age, body mass index, fasting, country, and smoking. We detected and quan

Journal article

Yang Y, Wu L, Shu X, Lu Y, Shu X-O, Cai Q, Beeghly-Fadiel A, Li B, Ye F, Berchuck A, Anton-Culver H, Banerjee S, Benitez J, Bjørge L, Brenton JD, Butzow R, Campbell IG, Chang-Claude J, Chen K, Cook LS, Cramer DW, DeFazio A, Dennis J, Doherty JA, Dork T, Eccles DM, Velez Edwards D, Fasching PA, Fortner RT, Gayther SA, Giles GG, Glasspool RM, Goode EL, Goodman MT, Gronwald J, Harris HR, Heitz F, Hildebrandt MAT, Høgdall E, Høgdall CK, Huntsman DG, Kar SP, Karlan BY, Kelemen LE, Kiemeney LA, Kjaer SK, Koushik A, Lambrechts D, Le ND, Levine DA, Massuger LFAG, Matsuo K, May T, McNeish IA, Menon U, Modugno F, Monteiro AN, Moorman PG, Moysich KB, Ness RB, Nevanlinna H, Olsson H, Onland-Moret NC, Park SK, Paul J, Pearce CL, Pejovic T, Phelan CM, Pike MC, Ramus SJ, Riboli E, Rodríguez-Antona C, Romieu I, Sandler DP, Schildkraut JM, Setiawan VW, Shan K, Siddiqui N, Sieh W, Stampfer MJ, Sutphen R, Swerdlow AJ, Szafron LM, Teo SH, Tworoger SS, Tyrer JP, Webb PM, Wentzensen N, White E, Willett WC, Wolk A, Woo YL, Wu AH, Yan L, Yannoukakos D, Chenevix-Trench G, Sellers TA, Pharoah PDP, Zheng W, Long Jet al., 2019, Genetic data from nearly 63,000 women of European descent predicts DNA methylation biomarkers and epithelial ovarian cancer risk, Cancer Research, Vol: 79, Pages: 505-517, ISSN: 1538-7445

DNA methylation is instrumental for gene regulation. Global changes in the epigenetic landscape have been recognized as a hallmark of cancer. However, the role of DNA methylation in epithelial ovarian cancer (EOC) remains unclear. In this study, high density genetic and DNA methylation data in white blood cells from the Framingham Heart Study (N=1,595) were used to build genetic models to predict DNA methylation levels. These prediction models were then applied to the summary statistics of a genome-wide association study (GWAS) of ovarian cancer including 22,406 EOC cases and 40,941 controls to investigate genetically predicted DNA methylation levels in association with EOC risk. Among 62,938 CpG sites investigated, genetically predicted methylation levels at 89 CpG were significantly associated with EOC risk at a Bonferroni-corrected threshold of P<7.94×10-7. Of them, 87 were located at GWAS-identified EOC susceptibility regions and two resided in a genomic region not previously reported to be associated with EOC risk. Integrative analyses of genetic, methylation, and gene expression data identified consistent directions of associations across 12 CpG, five genes, and EOC risk, suggesting that methylation at these 12 CpG may influence EOC risk by regulating expression of these five genes, namely MAPT, HOXB3, ABHD8, ARHGAP27 and SKAP1. We identified novel DNA methylation markers associated with EOC risk and propose that methylation at multiple CpG may affect EOC risk via regulation of gene expression.

Journal article

Schumacher FR, Olama AAA, Berndt SI, Benlloch S, Ahmed M, Saunders EJ, Dadaev T, Leongamornlert D, Anokian E, Cieza-Borrella C, Goh C, Brook MN, Sheng X, Fachal L, Dennis J, Tyrer J, Muir K, Lophatananon A, Stevens VL, Gapstur SM, Carter BD, Tangen CM, Goodman PJ, Thompson IM, Batra J, Chambers S, Moya L, Clements J, Horvath L, Tilley W, Risbridger GP, Gronberg H, Aly M, Nordström T, Pharoah P, Pashayan N, Schleutker J, Tammela TLJ, Sipeky C, Auvinen A, Albanes D, Weinstein S, Wolk A, Håkansson N, West CML, Dunning AM, Burnet N, Mucci LA, Giovannucci E, Andriole GL, Cussenot O, Cancel-Tassin G, Koutros S, Beane Freeman LE, Sorensen KD, Orntoft TF, Borre M, Maehle L, Grindedal EM, Neal DE, Donovan JL, Hamdy FC, Martin RM, Travis RC, Key TJ, Hamilton RJ, Fleshner NE, Finelli A, Ingles SA, Stern MC, Rosenstein BS, Kerns SL, Ostrer H, Lu Y-J, Zhang H-W, Feng N, Mao X, Guo X, Wang G, Sun Z, Giles GG, Southey MC, MacInnis RJ, FitzGerald LM, Kibel AS, Drake BF, Vega A, Gómez-Caamaño A, Szulkin R, Eklund M, Kogevinas M, Llorca J, Castaño-Vinyals G, Penney KL, Stampfer M, Park JY, Sellers TA, Lin H-Y, Stanford JL, Cybulski C, Wokolorczyk D, Lubinski J, Ostrander EA, Geybels MS, Nordestgaard BG, Nielsen SF, Weischer M, Bisbjerg R, Røder MA, Iversen P, Brenner H, Cuk K, Holleczek B, Maier C, Luedeke M, Schnoeller T, Kim J, Logothetis CJ, John EM, Teixeira MR, Paulo P, Cardoso M, Neuhausen SL, Steele L, Ding YC, De Ruyck K, De Meerleer G, Ost P, Razack A, Lim J, Teo S-H, Lin DW, Newcomb LF, Lessel D, Gamulin M, Kulis T, Kaneva R, Usmani N, Singhal S, Slavov C, Mitev V, Parliament M, Claessens F, Joniau S, Van den Broeck T, Larkin S, Townsend PA, Aukim-Hastie C, Gago-Dominguez M, Castelao JE, Martinez ME, Roobol MJ, Jenster G, van Schaik RHN, Menegaux F, Truong T, Koudou YA, Xu J, Khaw K-T, Cannon-Albright L, Pandha H, Michael A, Thibodeau SN, McDonnell SK, Schaid DJ, Lindstrom S, Turman C, Ma J, Hunter DJ, Riboli E, Siddiq A, Canzian F, Kolonel LN, Le Marchand L, Hoover RN, Macet al., 2019, Author Correction: Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci., Nat Genet, Vol: 51, Pages: 363-363

In the version of this article initially published, the name of author Manuela Gago-Dominguez was misspelled as Manuela Gago Dominguez. The error has been corrected in the HTML and PDF version of the article.

Journal article

Vrieling A, Bueno-De-Mesquita HB, Ros MM, Kampman E, Aben KK, Büchner FL, Jansen EH, Roswall N, Tjønneland A, Boutron-Ruault M-C, Cadeau C, Chang-Claude J, Kaaks R, Weikert S, Boeing H, Trichopoulou A, Lagiou P, Trichopoulos D, Sieri S, Palli D, Panico S, Peeters PH, Weiderpass E, Skeie G, Jakszyn P, Chirlaque M-D, Ardanaz E, Sánchez M-J, Ehrnström R, Malm J, Ljungberg B, Khaw K-T, Wareham NJ, Brennan P, Johansson M, Riboli E, Kiemeney LAet al., 2019, One-carbon metabolism biomarkers and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition, International Journal of Cancer, ISSN: 0020-7136

Published associations between dietary folate and bladder cancer risk are inconsistent. Biomarkers may provide more accurate measures of nutrient status. This nested case-control analysis within the European Prospective Investigation into Cancer and Nutrition (EPIC) investigated associations between pre-diagnostic serum folate, homocysteine, vitamins B6 and B12 and the risk of urothelial cell carcinomas of the bladder (UCC). A total of 824 patients with newly diagnosed UCC were matched with 824 cohort members. Serum folate, homocysteine, and vitamins B6 and B12 were measured. Odds ratios (OR) and 95% confidence intervals (CI) for total, aggressive, and non-aggressive UCC were estimated using conditional logistic regression with adjustment for smoking status, smoking duration and intensity, and other potential confounders. Additionally, statistical interaction with smoking status was assessed. A halving in serum folate concentrations was moderately associated with risk of UCC (OR: 1.18; 95% CI: 0.98-1.43), in particular aggressive UCC (OR: 1.34; 95% CI: 1.02-1.75; p-heterogeneity = 0.19). Compared to never smokers in the highest quartile of folate concentrations, this association seemed only apparent among current smokers in the lowest quartile of folate concentrations (OR: 6.26; 95% CI: 3.62-10.81, p-interaction = 0.07). Dietary folate was not associated with aggressive UCC (OR: 1.26; 95% CI: 0.81-1.95; p-heterogeneity = 0.14). No association was observed between serum homocysteine, vitamins B6 and B12 and risk of UCC. This study suggests that lower serum folate concentrations are associated with increased UCC risk, in particular aggressive UCC. Residual confounding by smoking cannot be ruled out and these findings require confirmation in future studies with multiple measurements.

Journal article

Gunter MJ, Alhomoud S, Arnold M, Brenner H, Burn J, Casey G, Chain AT, Cross AJ, Giovannucci E, Hoover R, Houlston R, Jenkins M, Laurent-Puig P, Peters U, Ransohoff D, Riboli E, Sinha R, Stadler ZK, Brennan P, Chanock SJet al., International cancer seminars:a focus on colorectal cancer, Annals of Oncology, ISSN: 0923-7534

Despite significant progress in our understanding of the etiology, biology and genetics of colorectal cancer, as well as important clinical advances, it remains the third most frequently diagnosed cancer worldwide and is the second leading cause of cancer death. Based on demographic projections, the global burden of colorectal cancer would be expected to rise by 72% from 1.8 million new cases in 2018 to over 3 million in 2040 with substantial increases anticipated in low and middle income countries. In this meeting report, we summarize the content of a joint workshop led by the National Cancer Institute (NCI) and the International Agency for Research on Cancer (IARC) which was held to summarize the important achievements that have been made in our understanding of colorectal cancer etiology, genetics, early detection and treatment and to identify key research questions that remain to be addressed.

Journal article

Matejcic M, Saunders EJ, Dadaev T, Brook MN, Wang K, Sheng X, Al Olama AA, Schumacher FR, Ingles SA, Govindasami K, Benlloch S, Berndt SI, Albanes D, Koutros S, Muir K, Stevens VL, Gapstur SM, Tangen CM, Batra J, Clements J, Gronberg H, Pashayan N, Schleutker J, Wolk A, West C, Mucci L, Kraft P, Cancel-Tassin G, Sorensen KD, Maehle L, Grindedal EM, Strom SS, Neal DE, Hamdy FC, Donovan JL, Travis RC, Hamilton RJ, Rosenstein B, Lu Y-J, Giles GG, Kibel AS, Vega A, Bensen JT, Kogevinas M, Penney KL, Park JY, Stanford JL, Cybulski C, Nordestgaard BG, Brenner H, Maier C, Kim J, Teixeira MR, Neuhausen SL, De Ruyck K, Razack A, Newcomb LF, Lessel D, Kaneva R, Usmani N, Claessens F, Townsend PA, Gago-Dominguez M, Roobol MJ, Menegaux F, Khaw K-T, Cannon-Albright LA, Pandha H, Thibodeau SN, Schaid DJ, Wiklund F, Chanock SJ, Easton DF, Eeles RA, Kote-Jarai Z, Conti DV, Haiman CA, Henderson BE, Stern MC, Thwaites A, Guy M, Whitmore I, Morgan A, Fisher C, Hazel S, Livni N, Cook M, Fachal L, Weinstein S, Freeman LEB, Hoover RN, Machiela MJ, Lophatananon A, Carter BD, Goodman P, Moya L, Srinivasan S, Kedda M-A, Yeadon T, Eckert A, Eklund M, Cavalli-Bjoerkman C, Dunning AM, Sipeky C, Hakansson N, Elliott R, Ranu H, Giovannucci E, Turman C, Hunter DJ, Cussenot O, Orntoft TF, Lane A, Lewis SJ, Davis M, Key TJ, Brown P, Kulkarni GS, Zlotta AR, Fleshner NE, Finelli A, Mao X, Marzec J, MacInnis RJ, Milne R, Hopper JL, Aguado M, Bustamante M, Castano-Vinyals G, Gracia-Lavedan E, Cecchini L, Stampfer M, Ma J, Sellers TA, Geybels MS, Park H, Zachariah B, Kolb S, Wokolorczyk D, Lubinski J, Kluzniak W, Nielsen SF, Weisher M, Cuk K, Vogel W, Luedeke M, Logothetis CJ, Paulo P, Cardoso M, Maia S, Silva MP, Steele L, Ding YC, De Meerleer G, De Langhe S, Thierens H, Lim J, Tan MH, Ong AT, Lin DW, Kachakova D, Mitkova A, Mitev V, Parliament M, Jenster G, Bangma C, Schroder FH, Truong T, Koudou YA, Michael A, Kierzek A, Karlsson A, Broms M, Wu H, Aukim-Hastie C, Tillmans L, Riska S, McDonnell SK, Deet al., 2019, Author Correction: Germline variation at 8q24 and prostate cancer risk in men of European ancestry, Nature Communications, Vol: 10, ISSN: 2041-1723

Correction to: Nature Communications; https://doi.org/10.1038/s41467-018-06863-1, published online 5 November 2018.The original version of this Article contained an error in the spelling of the author Manuela Gago-Dominguez, which was incorrectly given as Manuela G. Dominguez. This has now been corrected in both the PDF and HTML versions of the Article.

Journal article

Ward HA, Murphy N, Weiderpass E, Leitzmann MF, Aglago E, Gunter MJ, Freisling H, Jenab M, Boutron-Ruault M-C, Severi G, Carbonnel F, Kühn T, Kaaks R, Boeing H, Tjønneland A, Olsen A, Overvad K, Merino S, Zamora-Ros R, Rodríguez-Barranco M, Dorronsoro M, Chirlaque M-D, Barricarte A, Perez-Cornago A, Trichopoulou A, Bamia C, Lagiou P, Masala G, Grioni S, Tumino R, Sacerdote C, Mattiello A, Bueno-de-Mesquita B, Vermeulen R, Van Gils C, Nyström H, Rutegård M, Aune D, Riboli E, Cross AJet al., 2019, Gallstones and incident colorectal cancer in a large pan-European cohort study, International Journal of Cancer, ISSN: 0020-7136

Gallstones, a common gastrointestinal condition, can lead to several digestive complications and can result in inflammation. Risk factors for gallstones include obesity, diabetes, smoking and physical inactivity, all of which are known risk factors for colorectal cancer (CRC), as is inflammation. However, it is unclear whether gallstones are a risk factor for CRC. We examined the association between history of gallstones and CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a prospective cohort of over half a million participants from ten European countries. History of gallstones was assessed at baseline using a self-reported questionnaire. The analytic cohort included 334,986 participants; a history of gallstones was reported by 3,917 men and 19,836 women, and incident CRC was diagnosed among 1,832 men and 2,178 women (mean follow-up: 13.6 years). Hazard ratios (HR) and 95% confidence intervals (CI) for the association between gallstones and CRC were estimated using Cox proportional hazards regression models, stratified by sex, study centre and age at recruitment. The models were adjusted for body mass index, diabetes, alcohol intake and physical activity. A positive, marginally significant association was detected between gallstones and CRC among women in multivariable analyses (HR = 1.14, 95%CI 0.99-1.31, p = 0.077). The relationship between gallstones and CRC among men was inverse but not significant (HR = 0.81, 95%CI 0.63-1.04, p = 0.10). Additional adjustment for details of reproductive history or waist circumference yielded minimal changes to the observed associations. Further research is required to confirm the nature of the association between gallstones and CRC by sex.

Journal article

Huyghe JR, Bien SA, Harrison TA, Kang HM, Chen S, Schmit SL, Conti DV, Qu C, Jeon J, Edlund CK, Greenside P, Wainberg M, Schumacher FR, Smith JD, Levine DM, Nelson SC, Sinnott-Armstrong NA, Albanes D, Alonso MH, Anderson K, Arnau-Collell C, Arndt V, Bamia C, Banbury BL, Baron JA, Berndt SI, Bezieau S, Bishop DT, Boehm J, Boeing H, Brenner H, Brezina S, Buch S, Buchanan DD, Burnett-Hartman A, Butterbach K, Caan BJ, Campbell PT, Carlson CS, Castellvi-Bel S, Chan AT, Chang-Claude J, Chanock SJ, Chirlaque M-D, Cho SH, Connolly CM, Cross AJ, Cuk K, Curtis KR, de la Chapelle A, Doheny KF, Duggan D, Easton DF, Elias SG, Elliott F, English DR, Feskens EJM, Figueiredo JC, Fischer R, FitzGerald LM, Forman D, Gala M, Gallinger S, Gauderman WJ, Giles GG, Gillanders E, Gong J, Goodman PJ, Grady WM, Grove JS, Gsur A, Gunter MJ, Haile RW, Hampe J, Hampel H, Harlid S, Hayes RB, Hofer P, Hoffmeister M, Hopper JL, Hsu W-L, Huang W-Y, Hudson TJ, Hunter DJ, Ibanez-Sanz G, Idos GE, Ingersoll R, Jackson RD, Jacobs EJ, Jenkins MA, Joshi AD, Joshu CE, Keku TO, Key TJ, Kim HR, Kobayashi E, Kolonel LN, Kooperberg C, Kuehn T, Kury S, Kweon S-S, Larsson SC, Laurie CA, Le Marchand L, Leal SM, Lee SC, Lejbkowicz F, Lemire M, Li CI, Li L, Lieb W, Lin Y, Lindblom A, Lindor NM, Ling H, Louie TL, Mannisto S, Markowitz SD, Martin V, Masala G, McNeil CE, Melas M, Milne RL, Moreno L, Murphy N, Myte R, Naccarati A, Newcomb PA, Offit K, Ogino S, Onland-Moret NC, Pardini B, Parfrey PS, Pearlman R, Perduca V, Pharoah PDP, Pinchev M, Platz EA, Prentice RL, Pugh E, Raskin L, Rennert G, Rennert HS, Riboli E, Rodriguez-Barranco M, Romm J, Sakoda LC, Schafmayer C, Schoen RE, Seminara D, Shah M, Shelford T, Shin M-H, Shulman K, Sieri S, Slattery ML, Southey MC, Stadler ZK, Stegmaier C, Su Y-R, Tangen CM, Thibodeau SN, Thomas DC, Thomas SS, Toland AE, Trichopoulou A, Ulrich CM, Van den Berg DJ, van Duijnhoven FJB, Van Guelpen B, van Kranen H, Vijai J, Visvanathan K, Vodicka P, Vodickova L, Vymetalkova V, Weigl Ket al., 2019, Discovery of common and rare genetic risk variants for colorectal cancer, Nature Genetics, Vol: 51, Pages: 76-87, ISSN: 1061-4036

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10−8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.

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