Oral fungal profiling and risk of nasopharyngeal carcinoma: a population-based case-control studyResearch in context
Yufeng Chen,
Wanxin Li,
Ellen T. Chang,
Justine W. Debelius,
Lokeshwaran Manoharan,
Yuming Zheng,
Yancheng Li,
Guangwu Huang,
Hans-Olov Adami,
Rob Knight,
Yonglin Cai,
Zhe Zhang,
Weimin Ye
Affiliations
Yufeng Chen
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, 17177, Sweden
Wanxin Li
Department of Epidemiology and Health Statistics & Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China
Ellen T. Chang
Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, 94143, USA
Justine W. Debelius
Center for Translational Microbiome Research, Department of Microbiology, Tumor and Cancer Biology, Karolinska Institutet, Stockholm, 17177, Sweden; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA
Lokeshwaran Manoharan
National Bioinformatics Infrastructure Sweden (NBIS), Lund University, Lund, 22100, Sweden
Yuming Zheng
Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, 543002, China; Department of Preventive Medicine, Wuzhou Cancer Center, Wuzhou, 543002, China
Yancheng Li
Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, 543002, China; Cangwu Institute for Nasopharyngeal Carcinoma Control and Prevention, Wuzhou, 543002, China
Guangwu Huang
Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China; Key Laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education, Nanning, 530021, China
Hans-Olov Adami
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, 17177, Sweden; Clinical Effectiveness Group, Institute of Health and Society, University of Oslo, Oslo, NO-0316, Norway
Rob Knight
Department of Pediatrics, University of California San Diego, CA, 92093, USA
Yonglin Cai
Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, 543002, China; Department of Preventive Medicine, Wuzhou Cancer Center, Wuzhou, 543002, China; Corresponding author. Guangxi Health Commission Key Laboratory of Molecular Epidemiology of Nasopharyngeal Carcinoma, Wuzhou Red Cross Hospital, Wuzhou, 543002, China.
Zhe Zhang
Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China; Key Laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education, Nanning, 530021, China; Corresponding author. Department of Otolaryngology-Head & Neck Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, China.
Weimin Ye
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, 17177, Sweden; Department of Epidemiology and Health Statistics & Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China; Corresponding author. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, 171 77, Sweden.
Summary: Background: Dysbiosis of the oral mycobiome has been linked to some diseases, including cancers. However, the role of oral fungal communities in nasopharyngeal carcinoma (NPC) carcinogenesis has not previously been investigated. Methods: We characterized the oral salivary fungal mycobiome in 476 untreated incident NPC patients and 537 population-based controls using fungal internal transcribed spacer (ITS)-2 sequencing. The relationship between oral fungal mycobiome and the risk of NPC was assessed through bioinformatic and biostatistical analyses. Findings: We found that lower fungal alpha diversity was associated with an increased odds of NPC [lower vs. higher: observed features (adjusted odds ratio [OR] = 5.81, 95% confidence interval [CI] = 3.60–9.38); Simpson diversity (1.53, 1.03–2.29); Shannon diversity (2.03, 1.35–3.04)]. We also observed a significant difference in global fungal community patterns between cases and controls based on Bray–Curtis dissimilarity (P < 0.001). Carriage of oral fungal species, specifically, Saccharomyces cerevisiae, Candida tropicalis, Lodderomyces elongisporus, Candida albicans, and Fusarium poae, was associated with significantly higher odds of NPC, with ORs ranging from 1.56 to 4.66. Individuals with both low fungal and low bacterial alpha diversity had a profoundly elevated risk of NPC. Interpretation: Our results suggest that dysbiosis in the oral mycobiome, characterized by a loss of fungal community diversity and overgrowth of several fungal organisms, is associated with a substantially increased risk of NPC. Funding: This work was funded by the US National Institutes of Health, the Swedish Research Council, the High-level Talents Research Start-up Project of Fujian Medical University, and the China Scholarship Council.
