RT Journal Article
T1 Circulating bilirubin levels and risk of colorectal cancer: serological and Mendelian randomization analyses.
A1 Seyed Khoei, Nazlisadat
A1 Jenab, Mazda
A1 Murphy, Neil
A1 Banbury, Barbara L
A1 Carreras-Torres, Robert
A1 Viallon, Vivian
A1 Kühn, Tilman
A1 Bueno-de-Mesquita, Bas
A1 Aleksandrova, Krasimira
A1 Cross, Amanda J
A1 Weiderpass, Elisabete
A1 Stepien, Magdalena
A1 Bulmer, Andrew
A1 Tjønneland, Anne
A1 Boutron-Ruault, Marie-Christine
A1 Severi, Gianluca
A1 Carbonnel, Franck
A1 Katzke, Verena
A1 Boeing, Heiner
A1 Bergmann, Manuela M
A1 Trichopoulou, Antonia
A1 Karakatsani, Anna
A1 Martimianaki, Georgia
A1 Palli, Domenico
A1 Tagliabue, Giovanna
A1 Panico, Salvatore
A1 Tumino, Rosario
A1 Sacerdote, Carlotta
A1 Skeie, Guri
A1 Merino, Susana
A1 Bonet, Catalina
A1 Rodríguez-Barranco, Miguel
A1 Gil, Leire
A1 Chirlaque, Maria-Dolores
A1 Ardanaz, Eva
A1 Myte, Robin
A1 Hultdin, Johan
A1 Perez-Cornago, Aurora
A1 Aune, Dagfinn
A1 Tsilidis, Konstantinos K
A1 Albanes, Demetrius
A1 Baron, John A
A1 Berndt, Sonja I
A1 Bézieau, Stéphane
A1 Brenner, Hermann
A1 Campbell, Peter T
A1 Casey, Graham
A1 Chan, Andrew T
A1 Chang-Claude, Jenny
A1 Chanock, Stephen J
A1 Cotterchio, Michelle
A1 Gallinger, Steven
A1 Gruber, Stephen B
A1 Haile, Robert W
A1 Hampe, Jochen
A1 Hoffmeister, Michael
A1 Hopper, John L
A1 Hsu, Li
A1 Huyghe, Jeroen R
A1 Jenkins, Mark A
A1 Joshi, Amit D
A1 Kampman, Ellen
A1 Larsson, Susanna C
A1 Le Marchand, Loic
A1 Li, Christopher I
A1 Li, Li
A1 Lindblom, Annika
A1 Lindor, Noralane M
A1 Martín, Vicente
A1 Moreno, Victor
A1 Newcomb, Polly A
A1 Offit, Kenneth
A1 Ogino, Shuji
A1 Parfrey, Patrick S
A1 Pharoah, Paul D P
A1 Rennert, Gad
A1 Sakoda, Lori C
A1 Schafmayer, Clemens
A1 Schmit, Stephanie L
A1 Schoen, Robert E
A1 Slattery, Martha L
A1 Thibodeau, Stephen N
A1 Ulrich, Cornelia M
A1 van Duijnhoven, Franzel J B
A1 Weigl, Korbinian
A1 Weinstein, Stephanie J
A1 White, Emily
A1 Wolk, Alicja
A1 Woods, Michael O
A1 Wu, Anna H
A1 Zhang, Xuehong
A1 Ferrari, Pietro
A1 Anton, Gabriele
A1 Peters, Annette
A1 Peters, Ulrike
A1 Gunter, Marc J
A1 Wagner, Karl-Heinz
A1 Freisling, Heinz
K1 Anti-oxidants
K1 Bilirubin
K1 Cancer
K1 Colorectal cancer
K1 Mendelian randomization analysis
AB 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. 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  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, were suggestive of an inverse association with CRC in men, but not in women. These differences by sex did not reach formal statistical significance (Pheterogeneity ≥ 0.2). 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.
PB BioMed Central Ltd.
YR 2020
FD 2020-07-09
LK http://hdl.handle.net/10668/16196
UL http://hdl.handle.net/10668/16196
LA en
NO Seyed Khoei N, Jenab M, Murphy N, Banbury BL, Carreras-Torres R, Viallon V, et al. Circulating bilirubin levels and risk of colorectal cancer: serological and Mendelian randomization analyses. BMC Med. 2020 Sep 3;18(1):229.
DS RISalud
RD Apr 6, 2025