TY - JOUR
T1 - Association of oral microbiome with risk for incident head and neck squamous cell cancer
AU - Hayes, Richard B.
AU - Ahn, Jiyoung
AU - Fan, Xiaozhou
AU - Peters, Brandilyn A.
AU - Ma, Yingfei
AU - Yang, Liying
AU - Agalliu, Ilir
AU - Burk, Robert D.
AU - Ganly, Ian
AU - Purdue, Mark P.
AU - Freedman, Neal D.
AU - Gapstur, Susan M.
AU - Pei, Zhiheng
N1 - Funding Information:
Additional Contributions: We thank the PLCO Cancer Screening Trial investigators and the staff from Information Management Services Inc and Westat Inc for database support, sample selection, and study management. We also acknowledge the contribution to the Cancer Prevention Studies from central cancer registries, which are supported through the Centers for Disease Control and Prevention’s National Program of Cancer Registries and cancer registries supported by the National Cancer Institute’s Surveillance Epidemiology and End Results Program. Most importantly, we thank the participants of the American Cancer Society Cancer Prevention Study II Nutrition Cohort and the PLCO trial for their contributions that made this study possible.
Funding Information:
Funding/Support: This work was supported primarily by Public Health Service grant R01CA159036 and in part by the NYU Perlmutter Cancer Center Grant (P30CA016087), both of which were funded by the National Cancer Institute (NCI), National Institutes of Health. Additional support was from grants U01CA182370 and R01CA164964 from the NCI to NYU Langone Health and by grants R21CA152785 and P30CA013330 from the NCI to the Albert Einstein College of Medicine. The American Cancer Society supports the follow-up and maintenance of the Cancer Prevention Studies, which contributed data to this project. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was funded through a contract mechanism administered by the NCI’s Division of Cancer Prevention (DCP). The major DCP PLCO contracts were for 10 screening centers, a central laboratory, and a coordinating center. In addition, there was a separate DCP contract for a data management and analysis center. Additional contracts were provided by the intramural NCI Division of Cancer Epidemiology and Genetics to house and maintain the PLCO biorepository. ZP is a Staff Physician at the Department of Veterans Affairs New York Harbor Healthcare System.
Publisher Copyright:
© 2018 American Medical Association. All rights reserved.
PY - 2018/3
Y1 - 2018/3
N2 - IMPORTANCE Case-control studies show a possible relationship between oral bacteria and head and neck squamous cell cancer (HNSCC). Prospective studies are needed to examine the temporal relationship between oral microbiome and subsequent risk of HNSCC. OBJECTIVE To prospectively examine associations between the oral microbiome and incident HNSCC. DESIGN, SETTING, AND PARTICIPANTS This nested case-control study was carried out in 2 prospective cohort studies: the American Cancer Society Cancer Prevention Study II Nutrition Cohort (CPS-II) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Among 122 004 participants, 129 incident patient cases of HNSCC were identified during an average 3.9 years of follow-up. Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. All participants provided mouthwash samples and were cancer-free at baseline. EXPOSURES Oral microbiome composition and specific bacterial abundances were determined through bacterial 16S rRNA gene sequencing. Overall oral microbiome composition and specific taxa abundances were compared for the case group and the control group, using PERMANOVA and negative binomial generalized linear models, respectively, controlling for age, sex, race, cohort, smoking, alcohol, and oral human papillomavirus-16 status. Taxa with a 2-sided false discovery rate (FDR)-adjusted P value (q-value) <.10 were considered significant. MAIN OUTCOMES AND MEASURES Incident HNSCC. RESULTS The study included 58 patient cases from CPS-II (mean [SD] age, 71.0 [6.4] years; 16 [27.6%] women) and 71 patient cases from PLCO (mean [SD] age, 62.7 [4.8] years; 13 [18.3%] women). Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. Head and neck squamous cell cancer cases and controls were similar with respect to age, sex, and race. Patients in the case group were more often current tobacco smokers, tended to have greater alcohol consumption (among drinkers), and to be positive for oral carriage of papillomavirus-16. Overall microbiome composition was not associated with risk of HNSCC. Greater abundance of genera Corynebacterium (fold change [FC], 0.58; 95% confidence interval [CI], 0.41-0.80; q = .06) and Kingella (FC, 0.63; 95% CI, 0.46-0.86; q = .08) were associated with decreased risk of HNSCC, potentially owing to carcinogen metabolism capacity. These findings were consistent for both cohorts and by cohort follow-up time. The observed relationships tended to be stronger for larynx cancer and for individuals with a history of tobacco use. CONCLUSIONS AND RELEVANCE This study demonstrates that greater oral abundance of commensal Corynebacterium and Kingella is associated with decreased risk of HNSCC, with potential implications for cancer prevention.
AB - IMPORTANCE Case-control studies show a possible relationship between oral bacteria and head and neck squamous cell cancer (HNSCC). Prospective studies are needed to examine the temporal relationship between oral microbiome and subsequent risk of HNSCC. OBJECTIVE To prospectively examine associations between the oral microbiome and incident HNSCC. DESIGN, SETTING, AND PARTICIPANTS This nested case-control study was carried out in 2 prospective cohort studies: the American Cancer Society Cancer Prevention Study II Nutrition Cohort (CPS-II) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Among 122 004 participants, 129 incident patient cases of HNSCC were identified during an average 3.9 years of follow-up. Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. All participants provided mouthwash samples and were cancer-free at baseline. EXPOSURES Oral microbiome composition and specific bacterial abundances were determined through bacterial 16S rRNA gene sequencing. Overall oral microbiome composition and specific taxa abundances were compared for the case group and the control group, using PERMANOVA and negative binomial generalized linear models, respectively, controlling for age, sex, race, cohort, smoking, alcohol, and oral human papillomavirus-16 status. Taxa with a 2-sided false discovery rate (FDR)-adjusted P value (q-value) <.10 were considered significant. MAIN OUTCOMES AND MEASURES Incident HNSCC. RESULTS The study included 58 patient cases from CPS-II (mean [SD] age, 71.0 [6.4] years; 16 [27.6%] women) and 71 patient cases from PLCO (mean [SD] age, 62.7 [4.8] years; 13 [18.3%] women). Two controls per patient case (n = 254) were selected through incidence density sampling, matched on age, sex, race/ethnicity, and time since mouthwash collection. Head and neck squamous cell cancer cases and controls were similar with respect to age, sex, and race. Patients in the case group were more often current tobacco smokers, tended to have greater alcohol consumption (among drinkers), and to be positive for oral carriage of papillomavirus-16. Overall microbiome composition was not associated with risk of HNSCC. Greater abundance of genera Corynebacterium (fold change [FC], 0.58; 95% confidence interval [CI], 0.41-0.80; q = .06) and Kingella (FC, 0.63; 95% CI, 0.46-0.86; q = .08) were associated with decreased risk of HNSCC, potentially owing to carcinogen metabolism capacity. These findings were consistent for both cohorts and by cohort follow-up time. The observed relationships tended to be stronger for larynx cancer and for individuals with a history of tobacco use. CONCLUSIONS AND RELEVANCE This study demonstrates that greater oral abundance of commensal Corynebacterium and Kingella is associated with decreased risk of HNSCC, with potential implications for cancer prevention.
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U2 - 10.1001/jamaoncol.2017.4777
DO - 10.1001/jamaoncol.2017.4777
M3 - Article
C2 - 29327043
AN - SCOPUS:85045202813
VL - 4
SP - 358
EP - 365
JO - JAMA oncology
JF - JAMA oncology
SN - 2374-2437
IS - 3
ER -