Association between antibiotic use during early life and early-onset colorectal cancer risk overall and according to polygenic risk and FUT2 genotypes

Fangyuan Jiang, Daniel Boakye, Jing Sun, Lijuan Wang, Lili Yu, Xuan Zhou, Jianhui Zhao, Zilong Bian, Peige Song, Yazhou He, Yingshuang Zhu, Jie Chen, Shuai Yuan, Mingyang Song, Susanna C. Larsson, Edward L Giovannucci, Evropi Theodoratou*, Kefeng Ding*, Xue Li*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Early-onset colorectal cancer (EOCRC) has been increasing worldwide. Potential risk factors may have occurred in childhood or adolescence. We investigated the associations between early-life factors and EOCRC risk, with a particular focus on long-term or recurrent antibiotic use (LRAU) and its interaction with genetic factors. Data on the UK Biobank participants recruited between 2006 and 2010 and followed up to February 2022 were used. We used logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) of the associations between LRAU during early life and EOCRC risk overall and by polygenic risk score (constructed by 127 CRC-related genetic variants) and Fucosyltransferase 2 (FUT2), a gut microbiota regulatory gene. We also assessed the associations for early-onset colorectal adenomas, as precursor lesion of CRC, to examine the effect of LRAU during early-life and genetic factors on colorectal carcinogenesis. A total of 113 256 participants were included in the analysis, with 165 EOCRC cases and 719 EOCRA cases. LRAU was nominally associated with increased risk of early-onset CRC (OR = 1.48, 95% CI = 1.01-2.17, P =.046) and adenomas (OR = 1.40, 95% CI = 1.17-1.68, P <.001). When stratified by genetic polymorphisms of FUT2, LRAU appeared to confer a comparatively greater risk for early-onset adenomas among participants with rs281377 TT genotype (OR = 1.10, 95% CI = 0.79-1.52, P =.587, for CC genotype; OR = 1.75, 95% CI = 1.16-2.64, P =.008, for TT genotype; P interaction =.089). Our study suggested that LRAU during early life is associated with increased risk of early-onset CRC and adenomas, and the association for adenomas is predominant among individuals with rs281377 TT/CT genotype. Further studies investigating how LRAU contributes together with genetic factors to modify EOCRC risk, particularly concerning the microbiome-related pathway underlying colorectal carcinogenesis, are warranted.

Original languageEnglish
Pages (from-to)1602-1611
Number of pages10
JournalInternational Journal of Cancer
Volume153
Issue number9
Early online date28 Jul 2023
DOIs
Publication statusPublished - 1 Nov 2023

Keywords / Materials (for Non-textual outputs)

  • antibiotic use
  • early-life factors
  • early-onset colorectal cancer
  • FUT2 gene
  • polygenic risk

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