研究动态
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口腔微生物组和头颈鳞状细胞癌的后续风险。

Oral Microbiome and Subsequent Risk of Head and Neck Squamous Cell Cancer.

发表日期:2024 Sep 26
作者: Soyoung Kwak, Chan Wang, Mykhaylo Usyk, Feng Wu, Neal D Freedman, Wen-Yi Huang, Marjorie L McCullough, Caroline Y Um, Martha J Shrubsole, Qiuyin Cai, Huilin Li, Jiyoung Ahn, Richard B Hayes
来源: JAMA Oncology

摘要:

口腔微生物群可能与头颈鳞状细胞癌 (HNSCC) 的发生有关,但目前的证据很大程度上仅限于细菌 16S 扩增子测序或小型回顾性病例对照研究。 旨在测试口腔细菌和真菌微生物群是否与后续发生相关在 3 个流行病学队列、美国癌症协会癌症预防研究 II 营养队列、前列腺癌、肺癌、结直肠癌和卵巢癌筛查试验以及南方社区队列中提供口腔样本的参与者中进行前瞻性巢式病例对照研究学习。在平均 (SD) 5.1 (3.6) 年的随访期间,确定了 236 名预期发展为 HNSCC 的患者。根据队列、年龄、性别、种族和民族以及自口腔样本采集以来的时间进行 2:1 频率匹配,选择保持无 HNSCC 的对照参与者。数据分析于 2023 年进行。使用全基因组鸟枪法测序表征口腔细菌微生物组,使用内转录间隔区测序表征口腔真菌微生物组。通过分析微生物组的组成并进行偏差校正,评估细菌和真菌类群与 HNSCC 的关联。通过逻辑回归测试与红色和橙色口腔病原体复合物的关联。 HNSCC 风险的微生物风险评分是根据风险相关微生物群计算得出的。主要结局是 HNSCC 发病率。该研究纳入了 236 名 HNSCC 病例参与者,平均年龄 (SD) 为 60.9 (9.5) 岁,平均年龄为 24.6% 为女性。 5.1(3.6)年的随访,以及 485 名匹配的对照参与者。基线时的总体微生物组多样性与随后的 HNSCC 风险无关;然而,13 种口腔细菌被发现与 HNSCC 的发展存在差异相关。这些物种包括新发现的唾液普雷沃氏菌、血链球菌和纤毛菌属物种,以及属于β和γ变形菌纲的几种物种。红色/橙色牙周病原体复合体与 HNSCC 风险中度相关(比值比,1.06/1 SD;95% CI,1.00-1.12)。微生物风险评分(根据 22 种细菌创建)增加 1-SD 与 HNSCC 风险增加 50% 相关(多变量比值比,1.50;95% CI,1.21-1.85)。没有发现与 HNSCC 风险相关的真菌类群。这项病例对照研究提供了令人信服的证据,表明口腔细菌是 HNSCC 发展的危险因素。已鉴定的细菌和细菌复合物以及其他危险因素有望识别高危个体,以个性化预防 HNSCC。
The oral microbiota may be involved in development of head and neck squamous cell cancer (HNSCC), yet current evidence is largely limited to bacterial 16S amplicon sequencing or small retrospective case-control studies.To test whether oral bacterial and fungal microbiomes are associated with subsequent risk of HNSCC development.Prospective nested case-control study among participants providing oral samples in 3 epidemiological cohorts, the American Cancer Society Cancer Prevention Study II Nutrition Cohort, the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, and the Southern Community Cohort Study. Two hundred thirty-six patients who prospectively developed HNSCC were identified during a mean (SD) of 5.1 (3.6) years of follow-up. Control participants who remained HNSCC free were selected by 2:1 frequency matching on cohort, age, sex, race and ethnicity, and time since oral sample collection. Data analysis was conducted in 2023.Characterization of the oral bacterial microbiome using whole-genome shotgun sequencing and the oral fungal microbiome using internal transcribed spacer sequencing. Association of bacterial and fungal taxa with HNSCC was assessed by analysis of compositions of microbiomes with bias correction. Association with red and orange oral pathogen complexes was tested by logistic regression. A microbial risk score for HNSCC risk was calculated from risk-associated microbiota.The primary outcome was HNSCC incidence.The study included 236 HNSCC case participants with a mean (SD) age of 60.9 (9.5) years and 24.6% women during a mean of 5.1 (3.6) years of follow-up, and 485 matched control participants. Overall microbiome diversity at baseline was not related to subsequent HNSCC risk; however 13 oral bacterial species were found to be differentially associated with development of HNSCC. The species included the newly identified Prevotella salivae, Streptococcus sanguinis, and Leptotrichia species, as well as several species belonging to beta and gamma Proteobacteria. The red/orange periodontal pathogen complex was moderately associated with HNSCC risk (odds ratio, 1.06 per 1 SD; 95% CI, 1.00-1.12). A 1-SD increase in microbial risk score (created based on 22 bacteria) was associated with a 50% increase in HNSCC risk (multivariate odds ratio, 1.50; 95% CI, 1.21-1.85). No fungal taxa associated with HNSCC risk were identified.This case-control study yielded compelling evidence that oral bacteria are a risk factor for HNSCC development. The identified bacteria and bacterial complexes hold promise, along with other risk factors, to identify high-risk individuals for personalized prevention of HNSCC.