Host Genetic Associations with Salivary Microbiome in Oral Cancer

Author:

Yang S.F.12ORCID,Lin C.W.34,Chuang C.Y.56,Lee Y.C.7,Chung W.H.89,Lai H.C.1011,Chang L.C.12,Su S.C.8911

Affiliation:

1. Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan

2. Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan

3. Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan

4. Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan

5. School of Medicine, Chung Shan Medical University, Taichung, Taiwan

6. Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung, Taiwan

7. Department of Otolaryngology–Head and Neck Surgery, Chang Gung Memorial Hospital, Keelung, Taiwan

8. Whole-Genome Research Core Laboratory of Human Diseases, Chang Gung Memorial Hospital, Keelung, Taiwan

9. Department of Dermatology, Drug Hypersensitivity Clinical and Research Center, Chang Gung Memorial Hospital, Linkou, Taiwan

10. Department of Medical Biotechnology and Laboratory Science, and Microbiota Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan

11. Central Research Laboratory, XiaMen Chang Gung Hospital, XiaMen, China

12. Department of Mathematical Sciences, Florida Atlantic University, Boca Raton, FL, USA

Abstract

Despite the growing recognition of a host genetic effect on shaping gut microbiota composition, the genetic determinants of oral microbiota remain largely unexplored, especially in the context of oral diseases. Here, we performed a microbiome genome-wide association study in 2 independent cohorts of patients with oral squamous cell carcinoma (OSCC, n = 144 and 67) and an additional group of noncancer individuals ( n = 104). Besides oral bacterial dysbiosis and signatures observed in OSCC, associations of 3 loci with the abundance of genus-level taxa and 4 loci with β diversity measures were detected ( q < 0.05) at the discovery stage. The most significant hit (rs10906082 with the genus Lachnoanaerobaculum, P = 3.55 × 10–9 at discovery stage) was replicated in a second OSCC cohort. Moreover, the other 2 taxonomical associations, rs10973953 with the genus Kingella ( P = 1.38 × 10–9) and rs4721629 with the genus Parvimonas ( P = 3.53 × 10–8), were suggestive in the meta-analysis combining 2 OSCC cohorts. Further pathway analysis revealed that these loci were enriched for genes in regulation of oncogenic and angiogenic responses, implicating a genetic anchor to the oral microbiome in estimation of casual relationships with OSCC. Our findings delineate the role of host genotypes in influencing the structure of oral microbial communities.

Funder

Ministry of Health and Welfare

Chang Gung Memorial Hospital

Chung Shan Medical University Hospital

Publisher

SAGE Publications

Subject

General Dentistry

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