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2. P510 Relapse rate following withdrawal of vedolizumab and ustekinumab in patients with inflammatory bowel disease. The VEDUST-EXIT study

Author

Albshesh, A, primary, Kucha, P, additional, Mahajna, H, additional, Amiot, A, additional, Abitbol, C M, additional, Eder, P, additional, Imperatore, N, additional, Krznaric, Z, additional, Zaborowska, M, additional, Zagórowicz, E, additional, Carbonnel, F, additional, Zittan, E, additional, Ben-Horin, S, additional, and Kopylov, U, additional

Published
2024
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3. P900 A PROOF-OF-CONCEPT, PLACEBO-RANDOMIZED CONTROLLED TRIAL TARGETING ADHERENT AND INVASIVE ESCHERICHIA COLI (AIEC) WITH ANTIBIOTICS IN CROHN’S DISEASE: the TEOREM TRIAL

Author

Carbonnel, F, primary, Barnich, N, additional, Hébuterne, X, additional, Lepage, P, additional, Michiels, C, additional, Gilletta, C, additional, Wils, P, additional, Laharie, D, additional, Altwegg, R, additional, Allez, M, additional, Bouhnik, Y, additional, Agostini, H, additional, Molinari, D, additional, Ryan Balfour, S, additional, Colombel, J F, additional, Mary, J Y, additional, Walter-Petrich, A, additional, Chevret, S, additional, and Buisson, A, additional

Published
2024
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4. P663 Efficacy of jak inhibitors in inflammatory bowel disease patients with extraintestinal manifestations– Retrospective study

Author

Livne Margolin, M, primary, González Lama2, Y, additional, Koutroubakis, I, additional, Drygiannakis, I, additional, Shitrit, A, additional, Goldenberg, R, additional, Farkas, K, additional, Molnar, T, additional, Ivány, E, additional, Amiot, A, additional, Carbonnel, F, additional, Girod, P, additional, Doherty, G, additional, Mateescu, B, additional, Ben-Horin1, S, additional, and Kopylov, U, additional

Published
2024
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14. No association of alcohol use and the risk of ulcerative colitis or Crohn's disease: data from a European Prospective cohort study (EPIC)

Author

Bergmann, M M, Hernandez, V, Bernigau, W, Boeing, H, Chan, S S M, Luben, R, Khaw, K-T, Schaik, F van, Oldenburg, B., Bueno-de-Mesquita, B., Overvad, K., Palli, D., Masala, G., Carbonnel, F., Boutron-Ruault, M.C., Olsen, A., and Tjonneland, A.

Subjects
Ulcerative colitis -- Risk factors, Drinking of alcoholic beverages -- Health aspects, Crohn's disease -- Risk factors, Food/cooking/nutrition, Health
Abstract

Background/Objectives: The role of long-term alcohol consumption for the risk of developing ulcerative colitis (UC) and Crohn's disease (CD) is unclear. For the first time, to prospectively assess the role of pre-disease alcohol consumption on the risk of developing UC or CD. Subjects/Methods: Nested within the European Prospective Investigation into Cancer and Nutrition (EPIC-IBD), incident UC and CD cases and matched controls where included. At recruitment, participants completed validated food frequency and lifestyle questionnaires. Alcohol consumption was classified as either: non-use, former, light ([[less-than or slanted equal to]0.5 and 1 drink per week), below the recommended limits (BRL) ([[less-than or slanted equal to]1 and 2 drinks per day), moderate ([[less-than or slanted equal to]2.5 and 5 drinks per day), or heavy use (>2.5 and >5 drinks per day) for women and men, respectively; and was expressed as consumption at enrolment and during lifetime. Conditional logistic regression was applied adjusting for smoking and education, taking light users as the reference. Results: Out of 262 451 participants in six countries, 198 UC incident cases/792 controls and 84 CD cases/336 controls were included. At enrolment, 8%/27%/32%/23%/11% UC cases and 7%/29%/40%/19%/5% CD cases were: non-users, light, BRL, moderate and heavy users, respectively. The corresponding figures for lifetime non-use, former, light, BRL, moderate and heavy use were: 3%/5%/23%/44%/19%/6% and 5%/2%/25%/44%/23%/1% for UC and CD cases, respectively. There were no associations between any categories of alcohol consumption and risk of UC or CD in the unadjusted and adjusted odds ratios. Conclusion: There was no evidence of associations between alcohol use and the odds of developing either UC or CD., Author(s): M M Bergmann [sup.1] , V Hernandez [sup.1] [sup.2] , W Bernigau [sup.1] , H Boeing [sup.1] , S S M Chan [sup.3] [sup.4] , R Luben [sup.5] , [...]

Published
2017
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15. Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab

Author

Laharie, D, Bourreille, A, Branche, J, Allez, M, Bouhnik, Y, Filippi, J, Zerbib, F, Savoye, G, Vuitton, L, Moreau, J, Amiot, A, Cosnes, J, Ricart, E, Dewit, O, Lopez-Sanroman, A, Fumery, M, Carbonnel, F, Bommelaer, G, Coffin, B, Roblin, X, van Assche, G, Esteve, M, Farkkila, M, Gisbert, JP, Marteau, P, Nahon, S, de Vos, M, Lambert, J, Mary, JY, and Louis, E

Published
2018
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16. Étude rétrospective de la mise en place du certificat de compétences cliniques (C3) au format ECOS (examen clinique objectif structuré) au sein d’une faculté de médecine française

Author

Machouche, S., primary, Debien, B., additional, Mattatia, L., additional, Carbonnel, F., additional, Dupeyron, A., additional, Claret, P.G., additional, Thieblemont, T., additional, Cousin, S., additional, Capdevielle, D., additional, Morin, D., additional, Mondain, M., additional, Laffont, I., additional, and Guilpain, P., additional

Published
2022
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17. Obesity is Associated With Increased Risk of Crohn's disease, but not Ulcerative Colitis: A Pooled Analysis of Five Prospective Cohort Studies

Author

Casey, K., Olen, O., Ludvigsson, J.F., Carbonnel, F., Oldenburg, B., Gunter, M.J., Tjønneland, A., Grip, O., Amian, P., Barricarte, A., Bergmann, M.M., Boutron-Ruault, M.-C., Cross, A., Hart, A.R., Kaaks, R., Key, T., Chirlaque López, M.D., Luben, Robert, Masala, G., Manjer, J., Olsen, A., Overvad, K., Palli, D., Riboli, E., Sánchez, M.J., Tumino, R., Vermeulen, R., Verschuren, W.M.M., Wareham, N., Ananthakrishnan, A., Burke, K., Lopes, E.W., Lochhead, P., Chan, A.T., Wolk, A., Khalili, H., Casey, K., Olen, O., Ludvigsson, J.F., Carbonnel, F., Oldenburg, B., Gunter, M.J., Tjønneland, A., Grip, O., Amian, P., Barricarte, A., Bergmann, M.M., Boutron-Ruault, M.-C., Cross, A., Hart, A.R., Kaaks, R., Key, T., Chirlaque López, M.D., Luben, Robert, Masala, G., Manjer, J., Olsen, A., Overvad, K., Palli, D., Riboli, E., Sánchez, M.J., Tumino, R., Vermeulen, R., Verschuren, W.M.M., Wareham, N., Ananthakrishnan, A., Burke, K., Lopes, E.W., Lochhead, P., Chan, A.T., Wolk, A., and Khalili, H.

Abstract

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.

Published
2022

18. Obesity is Associated With Increased Risk of Crohn's disease, but not Ulcerative Colitis: A Pooled Analysis of Five Prospective Cohort Studies

Author

IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Casey, K., Olen, O., Ludvigsson, J.F., Carbonnel, F., Oldenburg, B., Gunter, M.J., Tjønneland, A., Grip, O., Amian, P., Barricarte, A., Bergmann, M.M., Boutron-Ruault, M.-C., Cross, A., Hart, A.R., Kaaks, R., Key, T., Chirlaque López, M.D., Luben, Robert, Masala, G., Manjer, J., Olsen, A., Overvad, K., Palli, D., Riboli, E., Sánchez, M.J., Tumino, R., Vermeulen, R., Verschuren, W.M.M., Wareham, N., Ananthakrishnan, A., Burke, K., Lopes, E.W., Lochhead, P., Chan, A.T., Wolk, A., Khalili, H., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Casey, K., Olen, O., Ludvigsson, J.F., Carbonnel, F., Oldenburg, B., Gunter, M.J., Tjønneland, A., Grip, O., Amian, P., Barricarte, A., Bergmann, M.M., Boutron-Ruault, M.-C., Cross, A., Hart, A.R., Kaaks, R., Key, T., Chirlaque López, M.D., Luben, Robert, Masala, G., Manjer, J., Olsen, A., Overvad, K., Palli, D., Riboli, E., Sánchez, M.J., Tumino, R., Vermeulen, R., Verschuren, W.M.M., Wareham, N., Ananthakrishnan, A., Burke, K., Lopes, E.W., Lochhead, P., Chan, A.T., Wolk, A., and Khalili, H.

Published
2022

19. P722 Prediagnostic serum vitamin D levels and risk of inflammatory bowel disease: a pan-European, nested case-control study

Author

Opstelten, J., Chan, S., Hart, A., van Schaik, F., Siersema, P., Lentjes, E., Khaw, K.-T., Luben, R., Key, T., Boeing, H., Bergmann, M., Overvad, K., Palli, D., Masala, G., Racine, A., Carbonnel, F., Boutron-Ruault, M.-C., Tjønneland, A., Olsen, A., Andersen, V., Kaaks, R., Kühn, T., Tumino, R., Trichopoulou, A., Verschuren, M., Witteman, B., and Oldenburg, B.

Published
2017
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28. COMBIO : efficacité et tolérance des associations de thérapies ciblées chez les patients atteints de maladies inflammatoires à médiation immunitaire

Author

Flachaire, B., primary, Guillo, L., additional, Avouac, J., additional, Nachury, M., additional, Carbonnel, F., additional, Bouguen, G., additional, Buisson, A., additional, Caillo, L., additional, Fumery, M., additional, Gilleta, C., additional, Hebuterne, X., additional, Lafforgue, P., additional, Laharie, D., additional, Mahé, E., additional, Marotte, H., additional, Nancey, S., additional, Ottaviani, S., additional, Salmon, J.H., additional, Guillaume, S., additional, Serrero, M., additional, Uzzan, M., additional, Viguier, M.A., additional, Richez, C., additional, Peyrin-Biroulet, L., additional, Seksik, P., additional, and Pham, T., additional

Published
2021
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31. Olmesartan-associated enteropathy: results of a national survey

Author

Marthey, L., Cadiot, G., Seksik, P., Pouderoux, P., Lacroute, J., Skinazi, F., Mesnard, B., Chayvialle, J. A., Savoye, G., Druez, A., Parlier, D., Abitbol, V., Gompel, M., Eoche, M., Poncin, E., Bobichon, R., Colardelle, P., Wils, P., Salloum, H., Peschard, S., Zerbib, F., Méresse, B., Cerf-Bensussan, N., Malamut, G., and Carbonnel, F.

Published
2014
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33. P272 Tofacitinib as salvage therapy for patients hospitalized with refractory severe active ulcerative colitis: a GETAID multicenter prospective/retrospective cohort

Author

Uzzan, M, primary, Bresteau, C, additional, Laharie, D, additional, Stefanescu, C, additional, Carbonnel, F, additional, Serrero, M, additional, Viennot, S, additional, Nachury, M, additional, Amiot, A, additional, Altwegg, R, additional, Picon, L, additional, Nahon, S, additional, Vuitton, L, additional, Ah Soune, P, additional, Kirchgesner, J, additional, Peyrin-Biroulet, L, additional, and Bouhnik, Y, additional

Published
2021
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37. Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author

Sanikini, H., Sophiea, M., Rinaldi, S., Agudo, A., Duell, E.J., Weiderpass, E., Overvad, K., Tjønneland, A., Halkjær, J., Boutron-Ruault, M.-C., Carbonnel, F., Cervenka, I., Boeing, H., Kaaks, R., Kühn, T., Trichopoulou, A., Martimianaki, G., Karakatsani, A., Pala, V., Palli, D., Mattiello, A., Tumino, R., Sacerdote, C., Skeie, G., Rylander, C., Chirlaque López, M.-D., Sánchez, M.-J., Ardanaz, E., Regnér, S., Stocks, T., Bueno-de-Mesquita, B., Vermeulen, R.C.H., Aune, D., Tong, T.Y.N., Kliemann, N., Murphy, N., Chadeau-Hyam, M., Gunter, M.J., Cross, A.J., IRAS OH Epidemiology Chemical Agents, and dIRAS RA-2

Subjects
reproductive, obesity, hormones, esophageal, cancer, gastric
Abstract

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m2: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. 98 vs. 0.82 vs. 84 vs. 2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs.

Published
2020

38. Circulating bilirubin levels and risk of colorectal cancer: serological and Mendelian randomization analyses

Author

Seyed Khoei, N., Jenab, M., Murphy, N., Banbury, B.L., Carreras-Torres, R., Viallon, V., Kühn, T., Bueno-de-Mesquita, B., Aleksandrova, K., Cross, A.J., Weiderpass, E., Stepien, M., Bulmer, A., Tjønneland, A., Boutron-Ruault, M.C., Severi, G., Carbonnel, F., Katzke, V., Boeing, H., Bergmann, M.M., Trichopoulou, A., Karakatsani, A., Martimianaki, G., Palli, D., Tagliabue, G., Panico, S., Tumino, R., Sacerdote, C., Skeie, G., Merino, S., Bonet, C., Rodríguez-Barranco, M., Gil, L., Chirlaque, M.D., Ardanaz, E., Myte, R., Hultdin, J., Perez-Cornago, A., Aune, D., Tsilidis, K.K., Albanes, D., Baron, J.A., Berndt, S.I., Bézieau, S., Brenner, H., Campbell, P.T., Casey, G., Chang-Claude, J., Chanock, S.J., Cotterchio, M., Gallinger, S., Gruber, S.B., Haile, R.W., Hampe, J., Hoffmeister, M., Hopper, J.L., Hsu, L., Huyghe, J.R., Jenkins, M.A., Joshi, A.D., Kampman, E., Larsson, S.C., Le Marchand, L., Li, C.I., Li, L., Lindblom, A., Lindor, N.M., Martín, V., Moreno, V., Newcomb, P.A., Offit, K., Ogino, S., Parfrey, P.S., Pharoah, P.D.P., Rennert, G., Sakoda, L.C., Schafmayer, C., Schmit, S.L., Schoen, R.E., Slattery, M.L., Thibodeau, S.N., Ulrich, C.M., van Duijnhoven, F.J.B., Weigl, K., Weinstein, S.J., White, E., Wolk, A., Woods, M.O., Wu, A.H., Zhang, X., Ferrari, P., Anton, G., Peters, A., Peters, U., Gunter, M.J., Wagner, K.H., and Freisling, H.

Subjects
Bilirubin, Cancer, Colorectal Cancer, Anti-oxidants, Mendelian Randomization Analysis
Abstract

Background Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex. Methods In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5 x 10(-8)) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study. Results The associations between circulating UCB levels and CRC risk differed by sex (P-heterogeneity = 0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the mainUGT1A1SNP (rs6431625), genetically predicted higher levels of total bilirubin were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12);P = 0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06);P = 0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, were suggestive of an inverse association with CRC in men, but not in women. These differences by sex did not reach formal statistical significance (P-heterogeneity >= 0.2). Conclusions Additional insight into the relationship between circulating bilirubin and CRC is needed in order to conclude on a potential causal role of bilirubin in CRC development.

Published
2020

39. Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author

Sanikini, H. Muller, D.C. Sophiea, M. Rinaldi, S. Agudo, A. Duell, E.J. Weiderpass, E. Overvad, K. Tjønneland, A. Halkjær, J. Boutron-Ruault, M.-C. Carbonnel, F. Cervenka, I. Boeing, H. Kaaks, R. Kühn, T. Trichopoulou, A. Martimianaki, G. Karakatsani, A. Pala, V. Palli, D. Mattiello, A. Tumino, R. Sacerdote, C. Skeie, G. Rylander, C. Chirlaque López, M.-D. Sánchez, M.-J. Ardanaz, E. Regnér, S. Stocks, T. Bueno-de-Mesquita, B. Vermeulen, R.C.H. Aune, D. Tong, T.Y.N. Kliemann, N. Murphy, N. Chadeau-Hyam, M. Gunter, M.J. Cross, A.J.

Abstract

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m2: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. 98 vs. 0.82 vs. 84 vs. 2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs.

Published
2020

40. Circulating bilirubin levels and risk of colorectal cancer: Serological and Mendelian randomization analyses

Author

Seyed Khoei, N. Jenab, M. Murphy, N. Banbury, B.L. Carreras-Torres, R. Viallon, V. Kühn, T. Bueno-De-Mesquita, B. Aleksandrova, K. Cross, A.J. Weiderpass, E. Stepien, M. Bulmer, A. Tjønneland, A. Boutron-Ruault, M.-C. Severi, G. Carbonnel, F. Katzke, V. Boeing, H. Bergmann, M.M. Trichopoulou, A. Karakatsani, A. Martimianaki, G. Palli, D. Tagliabue, G. Panico, S. Tumino, R. Sacerdote, C. Skeie, G. Merino, S. Bonet, C. Rodríguez-Barranco, M. Gil, L. Chirlaque, M.-D. Ardanaz, E. Myte, R. Hultdin, J. Perez-Cornago, A. Aune, D. Tsilidis, K.K. Albanes, D. Baron, J.A. Berndt, S.I. Bézieau, S. Brenner, H. Campbell, P.T. Casey, G. Chan, A.T. Chang-Claude, J. Chanock, S.J. Cotterchio, M. Gallinger, S. Gruber, S.B. Haile, R.W. Hampe, J. Hoffmeister, M. Hopper, J.L. Hsu, L. Huyghe, J.R. Jenkins, M.A. Joshi, A.D. Kampman, E. Larsson, S.C. Le Marchand, L. Li, C.I. Li, L. Lindblom, A. Lindor, N.M. Martín, V. Moreno, V. Newcomb, P.A. Offit, K. Ogino, S. Parfrey, P.S. Pharoah, P.D.P. Rennert, G. Sakoda, L.C. Schafmayer, C. Schmit, S.L. Schoen, R.E. Slattery, M.L. Thibodeau, S.N. Ulrich, C.M. Van Duijnhoven, F.J.B. Weigl, K. Weinstein, S.J. White, E. Wolk, A. Woods, M.O. Wu, A.H. Zhang, X. Ferrari, P. Anton, G. Peters, A. Peters, U. Gunter, M.J. Wagner, K.-H. Freisling, H.

Abstract

Background: Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex. Methods: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5 × 10-8) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study. Results: The associations between circulating UCB levels and CRC risk differed by sex (P heterogeneity = 0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12); P = 0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06); P = 0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, were suggestive of an inverse association with CRC in men, but not in women. These differences by sex did not reach formal statistical significance (P heterogeneity ≥ 0.2). Conclusions: Additional insight into the relationship between circulating bilirubin and CRC is needed in order to conclude on a potential causal role of bilirubin in CRC development. © 2020 The Author(s).

Published
2020

41. Antibody responses to helicobacter pylori and risk of developing colorectal cancer in a European cohort

Author

Butt, J. Jenab, M. Pawlita, M. Tjønneland, A. Kyrø, C. Boutron-Ruault, M.-C. Carbonnel, F. Dong, C. Kaaks, R. Kuhn, T. Boeing, H. Schulze, M.B. Trichopoulou, A. Karakatsani, A. Vecchia, C.L. Palli, D. Agnoli, C. Tumino, R. Sacerdote, C. Panico, S. Bueno-De-Mesquita, B. Vermeulen, R. Gram, I.T. Weiderpass, E. Borch, K.B. Quiros, J.R. Agudo, A. Rodríguez-Barranco, M. Santiuste, C. Ardanaz, E. van Guelpen, B. Harlid, S. Imaz, L. Perez-Cornago, A. Gunter, M.J. Zouiouich, S. Park, J.Y. Riboli, E. Cross, A.J. Heath, A.K. Waterboer, T. Hughes, D.J.

Subjects
bacterial infections and mycoses
Abstract

Background: While Helicobacter pylori (H. pylori) is the major cause of gastric cancer, it has also been suggested to be involved in colorectal cancer development. However, prospective studies addressing H. pylori and colorectal cancer are sparse and inconclusive. We assessed the association of antibody responses to H. pylori proteins with colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: We applied H. pylori multiplex serology to measure antibody responses to 13 H. pylori proteins in prediagnostic serum samples from 485 colorectal cancer cases and 485 matched controls nested within the EPIC study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable conditional logistic regression to estimate the association of H. pylori overall and protein-specific seropositivity with odds of developing colorectal cancer. Results: Fifty-one percent of colorectal cancer cases were H. pylori seropositive compared with 44% of controls, resulting in an OR of 1.36 (95% CI, 1.00–1.85). Among the 13 individual H. pylori proteins, the association was driven mostly by seropositivity to Helicobacter cysteine-rich protein C (HcpC; OR: 1.66; 95% CI, 1.19–2.30) and Vacuolating cytotoxin A (VacA) (OR: 1.34; 95% CI, 0.99–1.82), the latter being nonstatistically significant only in the fully adjusted model. Conclusions: In this prospective multicenter European study, antibody responses to H. pylori proteins, specifically HcpC and VacA, were associated with an increased risk of developing colorectal cancer. Impact: Biological mechanisms for a potential causal role of H. pylori in colorectal carcinogenesis need to be elucidated, and subsequently whether H. pylori eradication may decrease colorectal cancer incidence. © 2020 American Association for Cancer Research.

Published
2020

42. Inflammatory potential of the diet and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study

Author

Jakszyn, P. Cayssials, V. Buckland, G. Perez-Cornago, A. Weiderpass, E. Boeing, H. Bergmann, M.M. Vulcan, A. Ohlsson, B. Masala, G. Cross, A.J. Riboli, E. Ricceri, F. Dahm, C.C. Nyvang, D. Katzke, V.A. Kühn, T. Kyrø, C. Tjønneland, A. Ward, H.A. Tsilidis, K.K. Skeie, G. Sieri, S. Sanchez, M.-J. Huerta, J.M. Amiano, P. Lasheras, C. Ardanaz, E. Mahamat-Saleh, Y. Boutron-Ruault, M.-C. Carbonnel, F. Panico, S. Peppa, E. Trichopoulou, A. Karakatsani, A. Tumino, R. Vermeulen, R. Jenab, M. Gunter, M. Agudo, A.

Subjects
digestive system diseases
Abstract

Proinflammatory diets are associated with risk of developing colorectal cancer (CRC), however, inconsistencies exist in subsite- and sex-specific associations. The relationship between CRC and combined lifestyle-related factors that contribute toward a low-grade inflammatory profile has not yet been explored. We examined the association between the dietary inflammatory potential and an inflammatory profile and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. This cohort included 476,160 participants followed-up of 14 years and 5,991 incident CRC cases (3,897 colon and 2,094 rectal tumors). Dietary inflammatory potential was estimated using an Inflammatory Score of the Diet (ISD). An Inflammatory Profile Score (IPS) was constructed, incorporating the ISD, physical activity level and abdominal obesity. The associations between the ISD and CRC and IPS and CRC were assessed using multivariable regression models. More proinflammatory diets were related to a higher CRC risk, particularly for colon cancer; hazard ratio (HR) for highest versus lowest ISD quartile was 1.15 (95% confidence interval [CI] 1.04–1.27) for CRC, 1.24 (95% CI 1.09–1.41) for colon cancer and 0.99 (95% CI 0.83–1.17) for rectal cancer. Associations were more pronounced in men and not significant in women. The IPS was associated with CRC risk, particularly colon cancer among men; HRs for the highest versus lowest IPS was 1.62 (95% CI 1.31–2.01) for colon cancer overall and 2.11 (95% CI 1.50–2.97) for colon cancer in men. Our study shows that more proinflammatory diets and a more inflammatory profile are associated with higher risk of CRC, principally colon cancer and in men. © 2020 UICC

Published
2020

43. Antibody responses to helicobacter pylori and risk of developing colorectal cancer in a European cohort

Author

Butt, J., Jenab, M., Pawlita, M., Tjønneland, A., Kyrø, C., Boutron-Ruault, M.-C., Carbonnel, F., Dong, C., Kaaks, R., Kuhn, T., Boeing, H., Schulze, M.B., Trichopoulou, A., Karakatsani, A., Vecchia, C.L., Palli, D., Agnoli, C., Tumino, R., Sacerdote, C., Panico, S., Bueno-De-Mesquita, B., Vermeulen, R., Gram, I.T., Weiderpass, E., Borch, K.B., Quiros, J.R., Agudo, A., Rodríguez-Barranco, M., Santiuste, C., Ardanaz, E., van Guelpen, B., Harlid, S., Imaz, L., Perez-Cornago, A., Gunter, M.J., Zouiouich, S., Riboli, E., Cross, A.J., Heath, A.K., Waterboer, T., Hughes, D.J., Butt, J., Jenab, M., Pawlita, M., Tjønneland, A., Kyrø, C., Boutron-Ruault, M.-C., Carbonnel, F., Dong, C., Kaaks, R., Kuhn, T., Boeing, H., Schulze, M.B., Trichopoulou, A., Karakatsani, A., Vecchia, C.L., Palli, D., Agnoli, C., Tumino, R., Sacerdote, C., Panico, S., Bueno-De-Mesquita, B., Vermeulen, R., Gram, I.T., Weiderpass, E., Borch, K.B., Quiros, J.R., Agudo, A., Rodríguez-Barranco, M., Santiuste, C., Ardanaz, E., van Guelpen, B., Harlid, S., Imaz, L., Perez-Cornago, A., Gunter, M.J., Zouiouich, S., Riboli, E., Cross, A.J., Heath, A.K., Waterboer, T., and Hughes, D.J.

Abstract

Background: While Helicobacter pylori (H. pylori) is the major cause of gastric cancer, it has also been suggested to be involved in colorectal cancer development. However, prospective studies addressing H. pylori and colorectal cancer are sparse and inconclusive. We assessed the association of antibody responses to H. pylori proteins with colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods: We applied H. pylori multiplex serology to measure antibody responses to 13 H. pylori proteins in prediagnostic serum samples from 485 colorectal cancer cases and 485 matched controls nested within the EPIC study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable conditional logistic regression to estimate the association of H. pylori overall and protein-specific seropositivity with odds of developing colorectal cancer. Results: Fifty-one percent of colorectal cancer cases were H. pylori seropositive compared with 44% of controls, resulting in an OR of 1.36 (95% CI, 1.00–1.85). Among the 13 individual H. pylori proteins, the association was driven mostly by seropositivity to Helicobacter cysteine-rich protein C (HcpC; OR: 1.66; 95% CI, 1.19–2.30) and Vacuolating cytotoxin A (VacA) (OR: 1.34; 95% CI, 0.99–1.82), the latter being nonstatistically significant only in the fully adjusted model. Conclusions: In this prospective multicenter European study, antibody responses to H. pylori proteins, specifically HcpC and VacA, were associated with an increased risk of developing colorectal cancer. Impact: Biological mechanisms for a potential causal role of H. pylori in colorectal carcinogenesis need to be elucidated, and subsequently whether H. pylori eradication may decrease colorectal cancer incidence.

Published
2020

44. Inflammatory potential of the diet and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Author

Jakszyn, P, Cayssials, V, Buckland, G, Perez-Cornago, A, Weiderpass, E, Boeing, H, Bergmann, M M, Vulcan, A, Ohlsson, B, Masala, G, Cross, A J, Riboli, E, Ricceri, F, Dahm, C, Nyvang, D, Katzke, V A, Kühns, T, Kyrø, C, Tjønneland, A, Ward, H A, Tsilidis, K K, Skeie, G, Sieri, S, Sanchez, M J, Huerta, J M, Amiano, P, Lasheras, C, Ardanaz, E, Mahamat-Saleh, Y, Boutron-Ruault, M C, Carbonnel, F, Panico, S, Peppa, E, Trichopoulou, A, Karakatsani, A, Tumino, R, Vermeulen, R, Jenab, M, Gunter, M, Agudo, A, Jakszyn, P, Cayssials, V, Buckland, G, Perez-Cornago, A, Weiderpass, E, Boeing, H, Bergmann, M M, Vulcan, A, Ohlsson, B, Masala, G, Cross, A J, Riboli, E, Ricceri, F, Dahm, C, Nyvang, D, Katzke, V A, Kühns, T, Kyrø, C, Tjønneland, A, Ward, H A, Tsilidis, K K, Skeie, G, Sieri, S, Sanchez, M J, Huerta, J M, Amiano, P, Lasheras, C, Ardanaz, E, Mahamat-Saleh, Y, Boutron-Ruault, M C, Carbonnel, F, Panico, S, Peppa, E, Trichopoulou, A, Karakatsani, A, Tumino, R, Vermeulen, R, Jenab, M, Gunter, M, and Agudo, A

Abstract

Pro-inflammatory diets are associated with risk of developing colorectal cancer (CRC), however inconsistencies exist in subsite- and sex-specific associations. The relationship between CRC and combined lifestyle-related factors that contribute towards a low-grade inflammatory profile has not yet been explored. We examined the association between the dietary inflammatory potential and an inflammatory profile and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. This cohort included 476,160 participants followed-up of 14 years and 5,991 incident CRC cases (3,897 colon and 2,094 rectal tumours). Dietary inflammatory potential was estimated using an Inflammatory Score of the Diet (ISD). An Inflammatory Profile Score (IPS) was constructed, incorporating the ISD, physical activity level and abdominal obesity. The associations between the ISD and CRC and IPS and CRC were assessed using multivariable regression models. More pro- inflammatory diets were related to a higher CRC risk, particularly for colon cancer; Hazar Ratio (HR) for highest versus lowest ISD quartile was 1.15 (95% confidence interval (CI) 1.04-1.27) for CRC, 1.24 (95% CI 1.09-1.41) for colon cancer and 0.99 (95% CI 0.83-1.17) for rectal cancer. Associations were more pronounced in men and not significant in women. The IPS was associated with CRC risk, particularly colon cancer among men; HRs for the highest versus lowest IPS were 1.62 (95% CI 1.31- 2.01) for colon cancer overall and 2.11 (95% CI 1.50-2.97) for colon cancer in men. This study shows that more pro-inflammatory diets and a more inflammatory profile are associated with higher risk of CRC, principally colon cancer and in men. This article is protected by copyright. All rights reserved.

Published
2020

45. Interstitial and Granulomatous Lung Disease in Inflammatory Bowel Disease Patients

Author

Eliadou, E., Moleiro, J., Ribaldone, D.G., Astegiano, M., Rothfuss, K., Taxonera, C., Ghalim, F., Carbonnel, F., Verstockt, B., Festa, S., Maia, L., Berrozpe, A., Zagorowicz, E., Savarino, E., Ellul, P., Vavricka, S.R., Calvo, M., Koutroubakis, I., Hoentjen, F., Salazar, L.F., Callela, F., Pizarro, F.C., Soufleris, K., Sonnenberg, E., Cavicchi, M., Wypych, J., Hommel, C., Ghiani, A., Fiorino, G., Eliadou, E., Moleiro, J., Ribaldone, D.G., Astegiano, M., Rothfuss, K., Taxonera, C., Ghalim, F., Carbonnel, F., Verstockt, B., Festa, S., Maia, L., Berrozpe, A., Zagorowicz, E., Savarino, E., Ellul, P., Vavricka, S.R., Calvo, M., Koutroubakis, I., Hoentjen, F., Salazar, L.F., Callela, F., Pizarro, F.C., Soufleris, K., Sonnenberg, E., Cavicchi, M., Wypych, J., Hommel, C., Ghiani, A., and Fiorino, G.

Abstract

Contains fulltext : 220103.pdf (Publisher’s version ) (Closed access), BACKGROUND: Interstitial lung [ILD] disease and granulomatous lung disease [GLD] are rare respiratory disorders that have been associated with inflammatory bowel disease [IBD]. Clinical presentation is polymorphic and aetiology is unclear. METHODS: This was an ECCO-CONFER project. Cases of concomitant ILD or GLD and IBD, or drug-induced ILD/GLD, were collected. The criteria for diagnosing ILD and GLD were based on definitions from the American Thoracic Society and the European Respiratory Society and on the discretion of reporting clinician. RESULTS: We identified 31 patients with ILD. The majority had ulcerative colitis [UC] [n = 22]. Drug-related ILD was found in 64% of these patients, 25 patients [80.6%] required hospitalisation, and one required non-invasive ventilation. The causative drug was stopped in all drug-related ILD, and 87% of patients received systemic steroids. At follow-up, 16% of patients had no respiratory symptoms, 16% had partial improvement, 55% had ongoing symptoms, and there were no data in 13%. One patient was referred for lung transplantation, and one death from lung fibrosis was reported. We also identified 22 GLD patients: most had Crohn's disease [CD] [n = 17]. Drug-related GLD was found in 36% of patients and 10 patients [45.4%] required hospitalisation. The causative drug was stopped in all drug-related GLD, and 81% of patients received systemic steroids. Remission of both conditions was achieved in almost all patients. CONCLUSIONS: ILD and GLD, although rare, can cause significant morbidity. In our series, over half of cases were drug-related and therefore focused pharmacovigilance is needed to identify and manage these cases.

Published
2020

46. Antibody responses to helicobacter pylori and risk of developing colorectal cancer in a European cohort

Author

IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Butt, J., Jenab, M., Pawlita, M., Tjønneland, A., Kyrø, C., Boutron-Ruault, M.-C., Carbonnel, F., Dong, C., Kaaks, R., Kuhn, T., Boeing, H., Schulze, M.B., Trichopoulou, A., Karakatsani, A., Vecchia, C.L., Palli, D., Agnoli, C., Tumino, R., Sacerdote, C., Panico, S., Bueno-De-Mesquita, B., Vermeulen, R., Gram, I.T., Weiderpass, E., Borch, K.B., Quiros, J.R., Agudo, A., Rodríguez-Barranco, M., Santiuste, C., Ardanaz, E., van Guelpen, B., Harlid, S., Imaz, L., Perez-Cornago, A., Gunter, M.J., Zouiouich, S., Riboli, E., Cross, A.J., Heath, A.K., Waterboer, T., Hughes, D.J., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Butt, J., Jenab, M., Pawlita, M., Tjønneland, A., Kyrø, C., Boutron-Ruault, M.-C., Carbonnel, F., Dong, C., Kaaks, R., Kuhn, T., Boeing, H., Schulze, M.B., Trichopoulou, A., Karakatsani, A., Vecchia, C.L., Palli, D., Agnoli, C., Tumino, R., Sacerdote, C., Panico, S., Bueno-De-Mesquita, B., Vermeulen, R., Gram, I.T., Weiderpass, E., Borch, K.B., Quiros, J.R., Agudo, A., Rodríguez-Barranco, M., Santiuste, C., Ardanaz, E., van Guelpen, B., Harlid, S., Imaz, L., Perez-Cornago, A., Gunter, M.J., Zouiouich, S., Riboli, E., Cross, A.J., Heath, A.K., Waterboer, T., and Hughes, D.J.

Published
2020

47. Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author

IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Sanikini, H., Sophiea, M., Rinaldi, S., Agudo, A., Duell, E.J., Weiderpass, E., Overvad, K., Tjønneland, A., Halkjær, J., Boutron-Ruault, M.-C., Carbonnel, F., Cervenka, I., Boeing, H., Kaaks, R., Kühn, T., Trichopoulou, A., Martimianaki, G., Karakatsani, A., Pala, V., Palli, D., Mattiello, A., Tumino, R., Sacerdote, C., Skeie, G., Rylander, C., Chirlaque López, M.-D., Sánchez, M.-J., Ardanaz, E., Regnér, S., Stocks, T., Bueno-de-Mesquita, B., Vermeulen, R.C.H., Aune, D., Tong, T.Y.N., Kliemann, N., Murphy, N., Chadeau-Hyam, M., Gunter, M.J., Cross, A.J., IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, Sanikini, H., Sophiea, M., Rinaldi, S., Agudo, A., Duell, E.J., Weiderpass, E., Overvad, K., Tjønneland, A., Halkjær, J., Boutron-Ruault, M.-C., Carbonnel, F., Cervenka, I., Boeing, H., Kaaks, R., Kühn, T., Trichopoulou, A., Martimianaki, G., Karakatsani, A., Pala, V., Palli, D., Mattiello, A., Tumino, R., Sacerdote, C., Skeie, G., Rylander, C., Chirlaque López, M.-D., Sánchez, M.-J., Ardanaz, E., Regnér, S., Stocks, T., Bueno-de-Mesquita, B., Vermeulen, R.C.H., Aune, D., Tong, T.Y.N., Kliemann, N., Murphy, N., Chadeau-Hyam, M., Gunter, M.J., and Cross, A.J.

Published
2020

48. Circulating bilirubin levels and risk of colorectal cancer: serological and Mendelian randomization analyses

Author

Seyed Khoei, N, Jenab, M, Murphy, N, Banbury, BL, Carreras-Torres, R, Viallon, V, Kuehn, T, Bueno-de-Mesquita, B, Aleksandrova, K, Cross, AJ, Weiderpass, E, Stepien, M, Bulmer, A, Tjonneland, A, Boutron-Ruault, M-C, Severi, G, Carbonnel, F, Katzke, V, Boeing, H, Bergmann, MM, Trichopoulou, A, Karakatsani, A, Martimianaki, G, Palli, D, Tagliabue, G, Panico, S, Tumino, R, Sacerdote, C, Skeie, G, Merino, S, Bonet, C, Rodriguez-Barranco, M, Gil, L, Chirlaque, M-D, Ardanaz, E, Myte, R, Hultdin, J, Perez-Cornago, A, Aune, D, Tsilidis, K, Albanes, Baron, JA, Berndt, SI, Bezieau, S, Brenner, H, Campbell, PT, Casey, G, Chan, AT, Chang-Claude, J, Chanock, SJ, Cotterchio, M, Gallinger, S, Gruber, SB, Haile, RW, Hampe, J, Hoffmeister, M, Hopper, JL, Hsu, L, Huyghe, JR, Jenkins, MA, Joshi, AD, Kampman, E, Larsson, SC, Le Marchand, L, Li, CI, Li, L, Lindblom, A, Lindor, NM, Martin, V, Moreno, V, Newcomb, PA, Offit, K, Ogino, S, Parfrey, PS, Pharoah, PDP, Rennert, G, Sakoda, LC, Schafmayer, C, Schmit, SL, Schoen, RE, Slattery, ML, Thibodeau, SN, Ulrich, CM, van Duijnhoven, FJB, Weigl, K, Weinstein, SJ, White, E, Wolk, A, Woods, MO, Wu, AH, Zhang, X, Ferrari, P, Anton, G, Peters, A, Peters, U, Gunter, MJ, Wagner, K-H, Freisling, H, Seyed Khoei, N, Jenab, M, Murphy, N, Banbury, BL, Carreras-Torres, R, Viallon, V, Kuehn, T, Bueno-de-Mesquita, B, Aleksandrova, K, Cross, AJ, Weiderpass, E, Stepien, M, Bulmer, A, Tjonneland, A, Boutron-Ruault, M-C, Severi, G, Carbonnel, F, Katzke, V, Boeing, H, Bergmann, MM, Trichopoulou, A, Karakatsani, A, Martimianaki, G, Palli, D, Tagliabue, G, Panico, S, Tumino, R, Sacerdote, C, Skeie, G, Merino, S, Bonet, C, Rodriguez-Barranco, M, Gil, L, Chirlaque, M-D, Ardanaz, E, Myte, R, Hultdin, J, Perez-Cornago, A, Aune, D, Tsilidis, K, Albanes, Baron, JA, Berndt, SI, Bezieau, S, Brenner, H, Campbell, PT, Casey, G, Chan, AT, Chang-Claude, J, Chanock, SJ, Cotterchio, M, Gallinger, S, Gruber, SB, Haile, RW, Hampe, J, Hoffmeister, M, Hopper, JL, Hsu, L, Huyghe, JR, Jenkins, MA, Joshi, AD, Kampman, E, Larsson, SC, Le Marchand, L, Li, CI, Li, L, Lindblom, A, Lindor, NM, Martin, V, Moreno, V, Newcomb, PA, Offit, K, Ogino, S, Parfrey, PS, Pharoah, PDP, Rennert, G, Sakoda, LC, Schafmayer, C, Schmit, SL, Schoen, RE, Slattery, ML, Thibodeau, SN, Ulrich, CM, van Duijnhoven, FJB, Weigl, K, Weinstein, SJ, White, E, Wolk, A, Woods, MO, Wu, AH, Zhang, X, Ferrari, P, Anton, G, Peters, A, Peters, U, Gunter, MJ, Wagner, K-H, and Freisling, H

Abstract

BACKGROUND: Bilirubin, a byproduct of hemoglobin breakdown and purported anti-oxidant, is thought to be cancer preventive. We conducted complementary serological and Mendelian randomization (MR) analyses to investigate whether alterations in circulating levels of bilirubin are associated with risk of colorectal cancer (CRC). We decided a priori to perform analyses separately in men and women based on suggestive evidence that associations may differ by sex. METHODS: In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC), pre-diagnostic unconjugated bilirubin (UCB, the main component of total bilirubin) concentrations were measured by high-performance liquid chromatography in plasma samples of 1386 CRC cases and their individually matched controls. Additionally, 115 single-nucleotide polymorphisms (SNPs) robustly associated (P < 5 × 10-8) with circulating total bilirubin were instrumented in a 2-sample MR to test for a potential causal effect of bilirubin on CRC risk in 52,775 CRC cases and 45,940 matched controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colon Cancer Family Registry (CCFR), and the Colorectal Transdisciplinary (CORECT) study. RESULTS: The associations between circulating UCB levels and CRC risk differed by sex (Pheterogeneity = 0.008). Among men, higher levels of UCB were positively associated with CRC risk (odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.04-1.36; per 1-SD increment of log-UCB). In women, an inverse association was observed (OR = 0.86 (0.76-0.97)). In the MR analysis of the main UGT1A1 SNP (rs6431625), genetically predicted higher levels of total bilirubin were associated with a 7% increase in CRC risk in men (OR = 1.07 (1.02-1.12); P = 0.006; per 1-SD increment of total bilirubin), while there was no association in women (OR = 1.01 (0.96-1.06); P = 0.73). Raised bilirubin levels, predicted by instrumental variables excluding rs6431625, we

Published
2020

49. Inflammatory potential of the diet and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Author

One Health Chemisch, dIRAS RA-2, Jakszyn, P, Cayssials, V, Buckland, G, Perez-Cornago, A, Weiderpass, E, Boeing, H, Bergmann, M M, Vulcan, A, Ohlsson, B, Masala, G, Cross, A J, Riboli, E, Ricceri, F, Dahm, C, Nyvang, D, Katzke, V A, Kühns, T, Kyrø, C, Tjønneland, A, Ward, H A, Tsilidis, K K, Skeie, G, Sieri, S, Sanchez, M J, Huerta, J M, Amiano, P, Lasheras, C, Ardanaz, E, Mahamat-Saleh, Y, Boutron-Ruault, M C, Carbonnel, F, Panico, S, Peppa, E, Trichopoulou, A, Karakatsani, A, Tumino, R, Vermeulen, R, Jenab, M, Gunter, M, Agudo, A, One Health Chemisch, dIRAS RA-2, Jakszyn, P, Cayssials, V, Buckland, G, Perez-Cornago, A, Weiderpass, E, Boeing, H, Bergmann, M M, Vulcan, A, Ohlsson, B, Masala, G, Cross, A J, Riboli, E, Ricceri, F, Dahm, C, Nyvang, D, Katzke, V A, Kühns, T, Kyrø, C, Tjønneland, A, Ward, H A, Tsilidis, K K, Skeie, G, Sieri, S, Sanchez, M J, Huerta, J M, Amiano, P, Lasheras, C, Ardanaz, E, Mahamat-Saleh, Y, Boutron-Ruault, M C, Carbonnel, F, Panico, S, Peppa, E, Trichopoulou, A, Karakatsani, A, Tumino, R, Vermeulen, R, Jenab, M, Gunter, M, and Agudo, A

Published
2020

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