br c Laboratory of Vaccine
c Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health and Nutrition, 7-6-8 Asagi, Saito, Ibaraki-shi, Osaka, 567-0085, Japan
d Department of Oral and Maxillofacial Surgery, Southern TOHOKU Research Institute for Neuroscience, Southern TOHOKU General Hospital, 7-172 Yatsuyamada, Koriyama-shi, Fukushima, 963-8052, Japan e Department of Oral Microbiology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama-shi, Kanagawa, 230-8501, Japan
Received in revised form
Objectives: It is important to determine the cause of increasing oral cancer occurrence and mortality rates in Japan, because the mortality rate has recently decreased in other developed countries. The impact of microbiota in carcinogenesis, especially in the digestive tract has been reported. This study aimed to clarify the relationship between oral cancer and oral microbiota in Japanese patients.
Methods: DNA was extracted from salivary samples of 60 oral cancer patients and 80 non-cancer in-dividuals as controls. We performed metagenomic analysis using 16S rRNA amplicon sequencing. Sta-tistical analysis in this study was performed using R (version 3.5.0). Results: Oral cancer patients showed higher a-diversity compared to the control group, and the b-di-versity between the two groups differed significantly. Further, there was a significant difference in the abundance ratio of bacterial genera between the two groups. Peptostreptococcus, Fusobacterium, Allo-prevotella, and Capnocytophaga were more abundant in the cancer group compared to the control, whereas Rothia and Haemophilus were less abundant (p < 0.01). A negative correlation in the microbiota composition was confirmed between the operational taxonomic units (OTU) of genus Rothia and T-stage progression using the TNM classification method. We performed logistic regression analysis to investi-gate the impact factor for the oral cancer group, and the result showed that Chao 1 index and sex are statistically significant variables.
Conclusions: In this study, we observed an increased bacterial 31430-18-9 in oral cancer patients and found distribution changes for some bacteria.
© 2019 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.
In recent years, the occurrence of oral cancer has increased in developed countries, with an estimated 7000 new cases and 3000 deaths occurring annually in Japan alone. Oral cancer, which ac-counts for only 2e3% of all cancers, most commonly involves the
E-mail address: [email protected]tsurumi-u.ac.jp (T. Ohshima). 1 Yasuharu Takahashi and Jonguk Park equally contributed as first authors.
tongue, and is associated with an age-adjusted male to female ratio of 2:1. Approximately 90% of the pathological types of cancer are oral squamous cell carcinoma (OSCC). The choices for oral cancer therapy comprise surgical treatment, chemotherapy, and radiation. The five-year survival rate of oral cancer is said to be 60e80%; however, early detection of cancer increases the survival rate to approximately 90% [1,2]. The etiology of oral cancer is multifacto-rial. Chemical irritants, such as cigarette smoke and alcohol, are associated with the risk of oral cancer, along with physical irritation by poor dental prosthesis or other factors such as a human
papillomavirus infection. Thus, excessive drinking and smoking increase the risk of oral cancer. Chronic periodontitis has also been reported as a risk factor for oral cancer [3,4].
A relationship between gut microbiota and tumorigenesis in the digestive region has been reported previously. For example, Heli-cobacter pylori causes gastric cancer . Salmonella typhi and Fusobacterium are associated with gallbladder and colon cancer, respectively [6,7]. Further, a possible association between oral microbiota and colorectal cancer has been reported. Several oral taxa such as Streptococcus and Prevotella were found to be abundant in colorectal cancer patients compared to a healthy control group . Further, bacterial and fungal microbiota have been reported in association with oral cancer. Approximately 700 bacterial species and 10 Candida fungal species have been detected in the human oral cavity. However, there is no clarification about their association with the risk of oral cancer. Some studies have employed next-generation sequencing (NGS) to assess the oral microbiota associ-ated with oral cancer [9e11]. However, the number of subjects was too small, and samples of cancer lesions and healthy sites from the same subject were used in these studies. Therefore, the credibility of the findings is unclear. Most of these studies have been reported in USA and in Asian countries except Japan with national and regional differences in the oral microbiota composition . However, there is no large-scale report regarding the comparison of oral microbiota between oral cancer patients and non-cancer control groups in Japan.