METHODS: Reviewing literature and integrating relevant information facilitated the appraisal of this important topic. This article reviewed neonatal jaundice, the entry of bilirubin into the immature brain and how breastfeeding may impact jaundice in the neonate.
RESULTS: While some substances in breast milk may be responsible for jaundice on the one hand, there is an irrefutable spectrum of advantages conferred by continued breastfeeding, on the other. As the breastfed infant benefits from fewer infections, enhanced organ and physiological barrier maturity, as well as the prospect of genetic modification of certain diseases, these useful actions could also reduce risks of early jaundice and its complications.
DISCUSSION: An exciting field for further research, holistic integration of knowledge clarifies both the overall advantages of breastfeeding and wisdom of its continued counsel. In fact, breast milk jaundice may reflect a holistic expression of tissue protection and enhanced neonatal survival.
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 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, 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).
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.