IARC/WHO. The Global Cancer Observatory - Cancer Fact Sheets: Colorectal Cancer. Lyon: International Agency for Research on Cancer (IARC); 2020.

Kang MJ, Jung KW, Bang SH, Choi SH, Park EH, Yun EH, et al. Cancer Statistics in Korea: Incidence, Mortality, Survival, and Prevalence in 2020. Cancer Res Treat. 2023;55:385–99.

Article  PubMed  PubMed Central  Google Scholar 

Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.

Article  PubMed  CAS  Google Scholar 

Lasry A, Zinger A, Ben-Neriah Y. Inflammatory networks underlying colorectal cancer. Nat Immunol. 2016;17:230–40.

Article  PubMed  CAS  Google Scholar 

Wagner KH, Wallner M, Mölzer C, Gazzin S, Bulmer AC, Tiribelli C, et al. Looking to the horizon: the role of bilirubin in the development and prevention of age-related chronic diseases. Clin Sci. 2015;129:1–25.

Article  CAS  Google Scholar 

Sedlak TW, Saleh M, Higginson DS, Paul BD, Juluri KR, Snyder SH. Bilirubin and glutathione have complementary antioxidant and cytoprotective roles. Proc Natl Acad Sci USA. 2009;106:5171–6.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Rodrigues CMP, Solá S, Brito MA, Brites D, Moura JJG. Bilirubin directly disrupts membrane lipid polarity and fluidity, protein order, and redox status in rat mitochondria. J Hepatol. 2002;36:335–41.

Article  PubMed  CAS  Google Scholar 

Hansen TW, Mathiesen SB, Walaas SI. Bilirubin has widespread inhibitory effects on protein phosphorylation. Pediatr Res. 1996;39:1072–7.

Article  PubMed  CAS  Google Scholar 

Fevery J. Bilirubin in clinical practice: a review. Liver Int J Int Assoc Study Liver. 2008;28:592–605.

CAS  Google Scholar 

Buckley DB, Klaassen CD. Mechanism of gender-divergent UDP-glucuronosyltransferase mRNA expression in mouse liver and kidney. Drug Metab Dispos Biol Fate Chem. 2009;37:834–40.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Vítek L, Tiribelli C. Bilirubin: The yellow hormone? J Hepatol. 2021;75:1485–90.

Article  PubMed  Google Scholar 

Zucker SD, Horn PS, Sherman KE. Serum bilirubin levels in the U.S. population: gender effect and inverse correlation with colorectal cancer. Hepatol Balt Md. 2004;40:827–35.

Article  CAS  Google Scholar 

Ioannou GN, Liou IW, Weiss NS. Serum bilirubin and colorectal cancer risk: a population-based cohort study. Aliment Pharm Ther. 2006;23:1637–42.

Article  CAS  Google Scholar 

Jirásková A, Novotný J, Novotný L, Vodicka P, Pardini B, Naccarati A, et al. Association of serum bilirubin and promoter variations in HMOX1 and UGT1A1 genes with sporadic colorectal cancer. Int J Cancer. 2012;131:1549–55.

Article  PubMed  Google Scholar 

Kühn T, Sookthai D, Graf ME, Schübel R, Freisling H, Johnson T, et al. Albumin, bilirubin, uric acid and cancer risk: results from a prospective population-based study. Br J Cancer. 2017;117:1572–9.

Article  PubMed  PubMed Central  Google Scholar 

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;18:229.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Seyed Khoei N, Anton G, Peters A, Freisling H, Wagner KH. The Association between Serum Bilirubin Levels and Colorectal Cancer Risk: Results from the Prospective Cooperative Health Research in the Region of Augsburg (KORA) Study in Germany. Antioxidants. 2020;9:908.

Article  PubMed  PubMed Central  Google Scholar 

Seyed Khoei N, Wagner KH, Carreras-Torres R, Gunter MJ, Murphy N, Freisling H. Associations between Prediagnostic Circulating Bilirubin Levels and Risk of Gastrointestinal Cancers in the UK Biobank. Cancers. 2021;13:2749.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Inoguchi T, Nohara Y, Nojiri C, Nakashima N. Association of serum bilirubin levels with risk of cancer development and total death. Sci Rep. 2021;11:13224.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Kang TW, Kim HJ, Ju H, Kim JH, Jeon YJ, Lee HC, et al. Genome-wide association of serum bilirubin levels in Korean population. Hum Mol Genet. 2010;19:3672–8.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Kim YR, Choi CK, Lee YH, Choi SW, Kim HY, Shin MH, et al. Association between Albumin, Total Bilirubin, and Uric Acid Serum Levels and the Risk of Cancer: A Prospective Study in a Korean Population. Yonsei Med J. 2021;62:792–8.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Kim Y, Han BG, Group the K. Cohort Profile: The Korean Genome and Epidemiology Study (KoGES) Consortium. Int J Epidemiol. 2017;46:e20.

Article  PubMed  Google Scholar 

Health Examinees Study Group. The Health Examinees (HEXA) study: rationale, study design and baseline characteristics. Asian Pac J Cancer Prev APJCP. 2015;16:1591–7.

Article  PubMed  CAS  Google Scholar 

Ahn Y, Kwon E, Shim JE, Park MK, Joo Y, Kimm K, et al. Validation and reproducibility of food frequency questionnaire for Korean genome epidemiologic study. Eur J Clin Nutr. 2007;61:1435–41.

Article  PubMed  CAS  Google Scholar 

Kim J, Kim Y, Ahn YO, Paik HY, Ahn Y, Tokudome Y, et al. Development of a food frequency questionnaire in Koreans. Asia Pac J Clin Nutr. 2003;12:243–50.

PubMed  Google Scholar 

Kityo A, Lee SA. Longitudinal changes in high sensitivity C-reactive protein associated with serum uric acid in the Korean Genome and Epidemiology Study. Sci Rep. 2024;14:374.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Zucker SD, Goessling W, Hoppin AG. Unconjugated bilirubin exhibits spontaneous diffusion through model lipid bilayers and native hepatocyte membranes. J Biol Chem. 1999;274:10852–62.

Article  PubMed  CAS  Google Scholar 

Niknam M, Maleki MH, Khakshournia S, Rasouli M, Vakili O, Shafiee SM. Bilirubin, an endogenous antioxidant that affects p53 protein and its downstream apoptosis/autophagy-related genes in LS180 and SW480 cell culture models of colorectal cancer. Biochem Biophys Res Commun. 2023;672:161–7.

Article  PubMed  CAS  Google Scholar 

Kander MC, Cui Y, Liu Z. Gender difference in oxidative stress: a new look at the mechanisms for cardiovascular diseases. J Cell Mol Med. 2017;21:1024–32.

Article  PubMed  Google Scholar 

Cheng Z, Rios GR, King CD, Coffman BL, Green MD, Mojarrabi B, et al. Glucuronidation of catechol estrogens by expressed human UDP-glucuronosyltransferases (UGTs) 1A1, 1A3, and 2B7. Toxicol Sci J Soc Toxicol. 1998;45:52–7.

CAS  Google Scholar 

Bosma PJ, Chowdhury JR, Bakker C, Gantla S, de Boer A, Oostra BA, et al. The genetic basis of the reduced expression of bilirubin UDP-glucuronosyltransferase 1 in Gilbert’s syndrome. N Engl J Med. 1995;333:1171–5.

Article  PubMed  CAS  Google Scholar 

Keshavan P, Schwemberger SJ, Smith DLH, Babcock GF, Zucker SD. Unconjugated bilirubin induces apoptosis in colon cancer cells by triggering mitochondrial depolarization. Int J Cancer. 2004;112:433–45.

Article  PubMed  CAS  Google Scholar 

Corich L, Aranda A, Carrassa L, Bellarosa C, Ostrow JD, Tiribelli C. The cytotoxic effect of unconjugated bilirubin in human neuroblastoma SH-SY5Y cells is modulated by the expression level of MRP1 but not MDR1. Biochem J. 2009;417:305–12.

Article