Prospective study of oral microbiome and gastric cancer risk among Asian, African American and European American populations

Yaohua Yang, Jirong Long, Cong Wang, William J. Blot, Zhiheng Pei, Xiang Shu, Fen Wu, Nathaniel Rothman, Jie Wu, Qing Lan, Qiuyin Cai, Wei Zheng, Yu Chen, Xiao Ou Shu

Research output: Contribution to journalArticlepeer-review


Colonization of specific bacteria in the human mouth was reported to be associated with gastric cancer risk. However, previous studies were limited by retrospective study designs and low taxonomic resolutions. We performed a prospective case-control study nested within three cohorts to investigate the relationship between oral microbiome and gastric cancer risk. Shotgun metagenomic sequencing was employed to characterize the microbiome in prediagnostic buccal samples from 165 cases and 323 matched controls. Associations of overall microbial richness and abundance of microbial taxa, gene families and metabolic pathways with gastric cancer risk were evaluated via conditional logistic regression. Analyses were performed within each cohort, and results were combined by meta-analyses. We found that overall microbial richness was associated with decreased gastric cancer risk, with an odds ratio (OR) per standard deviation (SD) increase in Simpson's reciprocal index of 0.77 (95% confidence interval [CI] = 0.61-0.99). Nine taxa, 38 gene families and six pathways also showed associations with gastric cancer risk at P <.05. Neisseria mucosa and Prevotella pleuritidis were enriched, while Mycoplasma orale and Eubacterium yurii were depleted among cases with ORs and 95% CIs per SD increase in centered log-ratio transformed taxa abundance of 1.31 (1.03-1.67), 1.26 (1.00-1.57), 0.74 (0.59-0.94) and 0.80 (0.65-0.98), respectively. The top two gene families (P = 3.75 × 10−4 and 3.91 × 10−4) and pathways (P = 1.75 × 10−3 and 1.53 × 10−3) associated with gastric cancer were related to the decreased risk and are involved in hexitol metabolism. Our study supports the hypothesis that oral microbiota may play a role in gastric cancer etiology.

Original languageEnglish (US)
Pages (from-to)916-927
Number of pages12
JournalInternational Journal of Cancer
Issue number6
StatePublished - Mar 15 2022

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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