Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Oral Oncol. 2023 Feb;137:106305. doi: 10.1016/j.oraloncology.2022.106305. Epub 2023 Jan 5.
This nested case-control study in the NIH-AARP Diet and Health Study was carried out to prospectively investigate the relationship of oral microbiome with head and neck cancer (HNC).
56 incident HNC cases were identified, and 112 controls were incidence-density matched to cases. DNA extracted from pre-diagnostic oral wash samples was whole-genome shotgun metagenomic sequenced to measure the overall oral microbiome. ITS2 gene qPCR was used to measure the presence of fungi. ITS2 gene sequencing was performed on ITS2 gene qPCR positive samples. We computed taxonomic and functional alpha-diversity and beta-diversity metrics. The presence and relative abundance of groups of red-complex (e.g., Porphyromonas gingivalis) and/or orange-complex (e.g., Fusobacterium nucleatum) periodontal pathogens were compared between cases and controls using conditional logistic regression models and MiRKAT.
Participants with higher taxonomic microbial alpha-diversity had a non-statistically significant decreased risk of HNC. No case-control differences were found for beta diversity by MiRKAT model (all p > 0.05). A greater relative abundance of red-complex periodontal pathogens (OR = 0.51, 95 % CI = 0.26-1.00), orange-complex (OR = 0.38, 95 % CI = 0.18-0.83), and both complexes' pathogens (OR = 0.32, 95 % CI = 0.14-0.75), were associated with reduced risk of HNC. The presence of oral fungi was also strongly associated with reduced risk of HNC compared with controls (OR = 0.39, 95 % CI = 0.17-0.92).
Greater taxonomic alpha-diversity, the presence of oral fungi, and the presence or relative abundance of multiple microbial species, including the red- and orange-complex periodontal pathogens, were associated with reduced risk of HNC. Future studies with larger sample sizes are needed to evaluate these associations.
本巢式病例对照研究纳入了 NIH-AARP 饮食与健康研究中的人群，旨在前瞻性地研究口腔微生物组与头颈部癌症（HNC）之间的关系。
本研究共纳入 56 例新诊断的 HNC 病例，并按照病例匹配了 112 例对照。从预诊断的口腔冲洗样本中提取 DNA，进行全基因组 shotgun 宏基因组测序，以测量整体口腔微生物组。采用 ITS2 基因 qPCR 检测真菌的存在。对 ITS2 基因 qPCR 阳性样本进行 ITS2 基因测序。我们计算了分类和功能 alpha 多样性和 beta 多样性指标。采用条件逻辑回归模型和 MiRKAT 比较病例组和对照组中红复合群（如牙龈卟啉单胞菌）和/或橙复合群（如核梭杆菌）牙周病原体的存在和相对丰度。
分类微生物 alpha 多样性较高的参与者患 HNC 的风险呈非统计学显著降低。MiRKAT 模型未发现病例组与对照组之间 beta 多样性存在差异（所有 p 值>0.05）。红复合群牙周病原体（OR=0.51，95%CI=0.26-1.00）、橙复合群（OR=0.38，95%CI=0.18-0.83）和两者的病原体（OR=0.32，95%CI=0.14-0.75）的相对丰度较高与 HNC 风险降低相关。与对照组相比，口腔真菌的存在也与 HNC 风险降低显著相关（OR=0.39，95%CI=0.17-0.92）。
分类 alpha 多样性较高、口腔真菌的存在以及包括红复合群和橙复合群牙周病原体在内的多种微生物物种的存在或相对丰度与 HNC 风险降低相关。需要更大样本量的未来研究来评估这些关联。
