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Article ; Online: Epigenetic Aging and Hematopoietic Cell Transplantation in Patients With Severe Aplastic Anemia.

Alsaggaf, Rotana / Katta, Shilpa / Wang, Tao / Hicks, Belynda D / Zhu, Bin / Spellman, Stephen R / Lee, Stephanie J / Horvath, Steve / Gadalla, Shahinaz M

Transplantation and cellular therapy

2021 Volume 27, Issue 4, Page(s) 313.e1–313.e8

Abstract: Cellular aging in hematopoietic cell transplantation (HCT) is important in the context of immune reconstitution and age-related complications. Recently, several DNA-methylation (DNAm)-based biomarkers of aging known as "epigenetic clocks" have been ... ...

Abstract	Cellular aging in hematopoietic cell transplantation (HCT) is important in the context of immune reconstitution and age-related complications. Recently, several DNA-methylation (DNAm)-based biomarkers of aging known as "epigenetic clocks" have been introduced as novel tools to predict cellular age. Here, we used Cox proportional hazards models to assess the possible associations of donor pre-HCT DNAm age, and its post-HCT changes, using the recently published lifespan-associated epigenetic clock known as "DNAm-GrimAge," with outcomes among patients with severe aplastic anemia (SAA). The study included 732 SAA patients from the Transplant Outcomes in Aplastic Anemia project, who underwent unrelated donor HCT and for whom a donor pre-HCT blood DNA sample was available; 41 also had a post-HCT sample collected at day 100. In multivariable analyses, we found similar associations for donor chronological age and pre-HCT DNAm-GrimAge with post-HCT survival (hazard ratio [HR] per decade = 1.13; 95% confidence interval [CI], 0.99-1.28; P = .07 and HR = 1.14; 95% CI, 0.99-1.28; P = .06, respectively). In donors with 10+ years of GrimAge acceleration (ie, deviation from expected DNAm age for chronological age), elevated risks of chronic graft versus host disease (HR = 2.4; 95% CI, 1.21-4.65; P = .01) and possibly post-HCT mortality (HR = 1.79; 95% CI, 0.96-3.33; P = .07) were observed. In the subset with post-HCT samples, we observed a significant increase in DNAm-GrimAge in the first 100 days after HCT (median change 12.5 years, range 1.4 to 26.4). Higher DNAm-GrimAge after HCT was associated with inferior survival (HR per year = 1.11; 95% CI, 1.02-1.21; P = .01), predominantly within the first year after HCT. This study highlights the possible role cellular aging may play in HCT outcomes.
MeSH term(s)	Anemia, Aplastic/genetics ; Epigenesis, Genetic ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Unrelated Donors
Language	English
Publishing date	2021-01-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	3062231-1
ISSN	2666-6367
ISSN (online)	2666-6367
DOI	10.1016/j.jtct.2021.01.013
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Zs.A 5082: Show issues

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Article ; Online: Genetic testing in severe aplastic anemia is required for optimal hematopoietic cell transplant outcomes.

Blood

2024 Volume 140, Issue 8, Page(s) 909–921

Abstract: Patients with severe aplastic anemia (SAA) can have an unrecognized inherited bone marrow failure syndrome (IBMFS) because of phenotypic heterogeneity. We curated germline genetic variants in 104 IBMFS-associated genes from exome sequencing performed on ... ...

Abstract	Patients with severe aplastic anemia (SAA) can have an unrecognized inherited bone marrow failure syndrome (IBMFS) because of phenotypic heterogeneity. We curated germline genetic variants in 104 IBMFS-associated genes from exome sequencing performed on 732 patients who underwent hematopoietic cell transplant (HCT) between 1989 and 2015 for acquired SAA. Patients with pathogenic or likely pathogenic (P/LP) variants fitting known disease zygosity patterns were deemed unrecognized IBMFS. Carriers were defined as patients with a single P/LP variant in an autosomal recessive gene or females with an X-linked recessive P/LP variant. Cox proportional hazard models were used for survival analysis with follow-up until 2017. We identified 113 P/LP single-nucleotide variants or small insertions/deletions and 10 copy number variants across 42 genes in 121 patients. Ninety-one patients had 105 in silico predicted deleterious variants of uncertain significance (dVUS). Forty-eight patients (6.6%) had an unrecognized IBMFS (33% adults), and 73 (10%) were carriers. No survival difference between dVUS and acquired SAA was noted. Compared with acquired SAA (no P/LP variants), patients with unrecognized IBMFS, but not carriers, had worse survival after HCT (IBMFS hazard ratio [HR], 2.13; 95% confidence interval[CI], 1.40-3.24; P = .0004; carriers HR, 0.96; 95% CI, 0.62-1.50; P = .86). Results were similar in analyses restricted to patients receiving reduced-intensity conditioning (n = 448; HR IBMFS = 2.39; P = .01). The excess mortality risk in unrecognized IBMFS attributed to death from organ failure (HR = 4.88; P < .0001). Genetic testing should be part of the diagnostic evaluation for all patients with SAA to tailor therapeutic regimens. Carriers of a pathogenic variant in an IBMFS gene can follow HCT regimens for acquired SAA.
MeSH term(s)	Adult ; Anemia, Aplastic/diagnosis ; Anemia, Aplastic/genetics ; Anemia, Aplastic/therapy ; Congenital Bone Marrow Failure Syndromes ; Female ; Genetic Testing ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Transplantation Conditioning/methods
Language	English
Publishing date	2024-02-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2022016508
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Article ; Online: Prospective and Cross-sectional Associations of the Rectal Tissue Microbiome with Colorectal Adenoma Recurrence.

Byrd, Doratha A / Vogtmann, Emily / Ortega-Villa, Ana M / Wan, Yunhu / Gomez, Maria / Hogue, Stephanie / Warner, Andrew / Zhu, Bin / Dagnall, Casey / Jones, Kristine / Hicks, Belynda / Albert, Paul S / Murphy, Gwen / Sinha, Rashmi

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology

2022 Volume 32, Issue 3, Page(s) 435–443

Abstract: Background: The gut microbiome is plausibly associated with colorectal cancer risk; however, previous studies mostly investigated this association cross-sectionally. We investigated cross-sectional and prospective associations of the rectal tissue ... ...

Abstract	Background: The gut microbiome is plausibly associated with colorectal cancer risk; however, previous studies mostly investigated this association cross-sectionally. We investigated cross-sectional and prospective associations of the rectal tissue microbiome with adenoma recurrence in the Polyp Prevention Trial (PPT). Methods: PPT is a 4-year randomized clinical trial of the effect of a dietary intervention on adenoma recurrence among community members. We extracted DNA from rectal biopsies at baseline, end of year 1, and end of year 4 among 455 individuals and sequenced the V4 region of the 16S rRNA gene. At each timepoint, we investigated associations of alpha diversity, beta diversity, and presence and relative abundance of select taxa with adenoma recurrence using multivariable logistic regression. Results: Variation in beta diversity was primarily explained by subject and minimally by year of collection or time between biopsy and colonoscopy. Cross-sectionally, year 4 alpha diversity was strongly, inversely associated with adenoma prevalence [ORQ3 vs. Q1 Shannon index = 0.40 (95% confidence interval, CI: 0.21-0.76)]. Prospective alpha diversity associations (i.e., baseline/year 1 alpha diversity with adenoma recurrence 3-4 years later) were weak or null, as were cross-sectional and prospective beta diversity-adenoma associations. Bacteroides abundance was more strongly, positively associated with adenoma prevalence cross-sectionally than prospectively. Conclusions: Rectal tissue microbiome profiles may be associated with prevalent adenomas, with little evidence supporting prospective associations. Impact: Additional prospective studies, with serial fecal and tissue samples, to explore microbiome-colorectal cancer associations are needed. Eventually, it may be possible to use microbiome characteristics as intervenable risk factors or screening tools.
MeSH term(s)	Humans ; Prospective Studies ; RNA, Ribosomal, 16S ; Colorectal Neoplasms/epidemiology ; Adenoma/epidemiology ; Colonoscopy ; Microbiota
Chemical Substances	RNA, Ribosomal, 16S
Language	English
Publishing date	2022-12-16
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	1153420-5
ISSN	1538-7755 ; 1055-9965
ISSN (online)	1538-7755
ISSN	1055-9965
DOI	10.1158/1055-9965.EPI-22-0608
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Article ; Online: Impact of Transcript (p16/p14ARF) Alteration on Cancer Risk in CDKN2A Germline Pathogenic Variant Carriers.

Sargen, Michael R / Helgadottir, Hildur / Yang, Xiaohong R / Harland, Mark / Hatton, Jessica N / Jones, Kristine / Hicks, Belynda D / Hutchinson, Amy / Curry, Michael / Tucker, Margaret A / Goldstein, Alisa M / Pfeiffer, Ruth M

JNCI cancer spectrum

2022 Volume 6, Issue 6

Abstract: Background: Few studies have evaluated the relationship between CDKN2A germline pathogenic variants (GPV), transcript (p16/p14ARF) alteration, and cancer risk.: Methods: Standardized incidence ratios (SIRs) comparing cancer risk with the general ... ...

Abstract	Background: Few studies have evaluated the relationship between CDKN2A germline pathogenic variants (GPV), transcript (p16/p14ARF) alteration, and cancer risk. Methods: Standardized incidence ratios (SIRs) comparing cancer risk with the general population were calculated for 385 CDKN2A GPV carriers from 2 large cohorts (259 United States and 126 Swedish individuals) using Poisson regression; statistical significance was defined as P less than .002 (Bonferroni correction). Cumulative incidence is reported for melanoma and nonmelanoma cancer. Results: Incidence was increased for melanoma (SIR = 159.8, 95% confidence interval [CI] = 132.1 to 193.2), pancreatic cancer (SIR = 24.1, 95% CI = 14.7 to 39.4), head and neck squamous cell carcinoma (SIR = 16.2, 95% CI = 9.5 to 27.6), and lung cancer (SIR = 5.6, 95% CI = 3.4 to 9.1) in GPV carriers. Similar associations were observed with p16 alteration. Combined p16 and p14ARF alteration was associated with increased incidence of esophageal cancer (SIR = 16.7, 95% CI = 5.7 to 48.9) and malignant peripheral nerve sheath tumor (SIR = 113.0, 95% CI = 16.4 to 780.9), although cancer events were limited (n < 5 for each malignancy). Cumulative incidence at age 70 years for melanoma and nonmelanoma cancer was 68.3% (95% CI = 68.0% to 68.6%) and 35.2% (95% CI = 34.9% to 35.6%), respectively. A total 89% of smoking-related cancers (lung, head and neck squamous cell carcinoma, pancreatic, esophageal) occurred in ever smokers. Conclusion: These findings highlight the impact of p16 and p14ARF alteration on cancer risk. Smoking was an important risk factor for smoking-related cancers in our study.
MeSH term(s)	Humans ; United States ; Aged ; Tumor Suppressor Protein p14ARF/genetics ; Squamous Cell Carcinoma of Head and Neck/epidemiology ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Melanoma/epidemiology ; Risk Factors ; Head and Neck Neoplasms
Chemical Substances	Tumor Suppressor Protein p14ARF ; Cyclin-Dependent Kinase Inhibitor p16 ; CDKN2A protein, human
Language	English
Publishing date	2022-10-21
Publishing country	England
Document type	Journal Article
ISSN	2515-5091
ISSN (online)	2515-5091
DOI	10.1093/jncics/pkac074
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Article ; Online: Telomere length and epigenetic clocks as markers of cellular aging: a comparative study.

Pearce, Emily E / Alsaggaf, Rotana / Katta, Shilpa / Dagnall, Casey / Aubert, Geraldine / Hicks, Belynda D / Spellman, Stephen R / Savage, Sharon A / Horvath, Steve / Gadalla, Shahinaz M

GeroScience

2022 Volume 44, Issue 3, Page(s) 1861–1869

Abstract: Telomere length (TL) and DNA methylation-based epigenetic clocks are markers of biological age, but the relationship between the two is not fully understood. Here, we used multivariable regression models to evaluate the relationships between leukocyte TL ...

Abstract	Telomere length (TL) and DNA methylation-based epigenetic clocks are markers of biological age, but the relationship between the two is not fully understood. Here, we used multivariable regression models to evaluate the relationships between leukocyte TL (LTL; measured by qPCR [n = 635] or flow FISH [n = 144]) and five epigenetic clocks (Hannum, DNAmAge pan-tissue, PhenoAge, SkinBlood, or GrimAge clocks), or their epigenetic age acceleration measures in healthy adults (age 19-61 years). LTL showed statistically significant negative correlations with all clocks (qPCR: r = - 0.26 to - 0.32; flow FISH: r = - 0.34 to - 0.49; p < 0.001 for all). Yet, models adjusted for age, sex, and race revealed significant associations between three of five clocks (PhenoAge, GrimAge, and Hannum clocks) and LTL by flow FISH (p < 0.01 for all) or qPCR (p < 0.001 for all). Significant associations between age acceleration measures for the same three clocks and qPCR or flow FISH TL were also found (p < 0.01 for all). Additionally, LTL (by qPCR or flow FISH) showed significant associations with extrinsic epigenetic age acceleration (EEAA: p < 0.0001 for both), but not intrinsic epigenetic age acceleration (IEAA; p > 0.05 for both). In conclusion, the relationships between LTL and epigenetic clocks were limited to clocks reflecting phenotypic age. The observed association between LTL and EEAA reflects the ability of both measures to detect immunosenescence. The observed modest correlations between LTL and epigenetic clocks highlight a possible benefit from incorporating both measures in understanding disease etiology and prognosis.
MeSH term(s)	Biomarkers ; Cellular Senescence ; DNA Methylation ; Epigenesis, Genetic ; Epigenomics ; Humans ; Telomere/genetics
Chemical Substances	Biomarkers
Language	English
Publishing date	2022-05-18
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2886586-8
ISSN	2509-2723 ; 2509-2715
ISSN (online)	2509-2723
ISSN	2509-2715
DOI	10.1007/s11357-022-00586-4
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Article ; Online: SomaticCombiner: improving the performance of somatic variant calling based on evaluation tests and a consensus approach.

Wang, Mingyi / Luo, Wen / Jones, Kristine / Bian, Xiaopeng / Williams, Russell / Higson, Herbert / Wu, Dongjing / Hicks, Belynda / Yeager, Meredith / Zhu, Bin

Scientific reports

2020 Volume 10, Issue 1, Page(s) 12898

Abstract: It is challenging to identify somatic variants from high-throughput sequence reads due to tumor heterogeneity, sub-clonality, and sequencing artifacts. In this study, we evaluated the performance of eight primary somatic variant callers and multiple ... ...

Abstract	It is challenging to identify somatic variants from high-throughput sequence reads due to tumor heterogeneity, sub-clonality, and sequencing artifacts. In this study, we evaluated the performance of eight primary somatic variant callers and multiple ensemble methods using both real and synthetic whole-genome sequencing, whole-exome sequencing, and deep targeted sequencing datasets with the NA12878 cell line. The test results showed that a simple consensus approach can significantly improve performance even with a limited number of callers and is more robust and stable than machine learning based ensemble approaches. To fully exploit the multi-callers, we also developed a software package, SomaticCombiner, that can combine multiple callers and integrates a new variant allelic frequency (VAF) adaptive majority voting approach, which can maintain sensitive detection for variants with low VAFs.
MeSH term(s)	Algorithms ; Computational Biology ; Databases, Nucleic Acid ; Exome ; High-Throughput Nucleotide Sequencing ; Humans ; Neoplasms/genetics ; Polymorphism, Single Nucleotide ; Software
Language	English
Publishing date	2020-07-30
Publishing country	England
Document type	Evaluation Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-69772-8
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Article ; Online: DNA-methylation-based telomere length estimator: comparisons with measurements from flow FISH and qPCR.

Pearce, Emily E / Horvath, Steve / Katta, Shilpa / Dagnall, Casey / Aubert, Geraldine / Hicks, Belynda D / Spellman, Stephen R / Katki, Hormuzd / Savage, Sharon A / Alsaggaf, Rotana / Gadalla, Shahinaz M

Aging

2021 Volume 13, Issue 11, Page(s) 14675–14686

Abstract: Telomere length (TL) is a marker of biological aging associated with several health outcomes. High throughput reproducible TL measurements are needed for large epidemiological studies. We compared the novel DNA methylation-based estimator (DNAmTL) with ... ...

Abstract	Telomere length (TL) is a marker of biological aging associated with several health outcomes. High throughput reproducible TL measurements are needed for large epidemiological studies. We compared the novel DNA methylation-based estimator (DNAmTL) with the high-throughput quantitative PCR (qPCR) and the highly accurate flow cytometry with fluorescent
MeSH term(s)	Adult ; DNA Methylation/genetics ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Real-Time Polymerase Chain Reaction ; Reproducibility of Results ; Telomere Homeostasis/genetics ; Young Adult
Language	English
Publishing date	2021-06-03
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
ISSN	1945-4589
ISSN (online)	1945-4589
DOI	10.18632/aging.203126
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Article ; Online: Evaluation of alcohol-free mouthwash for studies of the oral microbiome.

PloS one

2023 Volume 18, Issue 4, Page(s) e0284956

Abstract: Oral bacteria play important roles in human health and disease. Oral samples collected using ethanol-containing mouthwash are widely used for oral microbiome studies. However, ethanol is flammable and not ideal for transportation/storage in large ... ...

Abstract	Oral bacteria play important roles in human health and disease. Oral samples collected using ethanol-containing mouthwash are widely used for oral microbiome studies. However, ethanol is flammable and not ideal for transportation/storage in large quantities, and some individuals may avoid ethanol due to the burning sensation or due to various personal, medical, religious, and/or cultural factors. Here, we compared ethanol-free and ethanol-containing mouthwashes using multiple microbiome metrics and assessed the stability of the mouthwash samples stored up to 10 days before processing. Forty volunteers provided oral wash samples collected using ethanol-free and ethanol-containing mouthwashes. From each sample, one aliquot was immediately frozen, one was stored at 4°C for 5 days and frozen, while the third aliquot was stored for 5 days at 4°C and 5 days at ambient temperature to mimic shipping delays and then frozen. DNA was extracted, the 16S rRNA gene V4 region was amplified and sequenced, and bioinformatic processing was performed using QIIME 2. Microbiome metrics measured in the two mouthwash types were very similar, with intraclass correlation coefficients (ICCs) for alpha and beta diversity metrics greater than 0.85. Relative abundances of some taxa were significantly different, but ICCs of the top four most abundant phyla and genera were high (> 0.75) for the comparability of the mouthwashes. Stability during delayed processing was also high for both mouthwashes based on alpha and beta diversity measures and relative abundances of the top four phyla and genera (ICCs ≥ 0.90). These results demonstrate ethanol-free mouthwash performs similarly to ethanol-containing mouthwash for microbial analyses, and both mouthwashes are stable for at least 10 days without freezing prior to laboratory processing. Ethanol-free mouthwash is suitable for collecting and shipping oral wash samples, and these results have important implications for planning future epidemiologic studies of the oral microbiome.
MeSH term(s)	Humans ; Mouthwashes/pharmacology ; RNA, Ribosomal, 16S/genetics ; Microbiota/genetics ; Ethanol ; Bacteria/genetics
Chemical Substances	Mouthwashes ; RNA, Ribosomal, 16S ; Ethanol (3K9958V90M)
Language	English
Publishing date	2023-04-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0284956
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Article ; Online: Integrated Analysis of Coexpression and Exome Sequencing to Prioritize Susceptibility Genes for Familial Cutaneous Melanoma.

Yepes, Sally / Tucker, Margaret A / Koka, Hela / Xiao, Yanzi / Zhang, Tongwu / Jones, Kristine / Vogt, Aurelie / Burdette, Laurie / Luo, Wen / Zhu, Bin / Hutchinson, Amy / Yeager, Meredith / Hicks, Belynda / Brown, Kevin M / Freedman, Neal D / Chanock, Stephen J / Goldstein, Alisa M / Yang, Xiaohong R

The Journal of investigative dermatology

2022 Volume 142, Issue 9, Page(s) 2464–2475.e5

Abstract: The application of whole-exome sequencing has led to the identification of high- and moderate-risk variants that contribute to cutaneous melanoma susceptibility. However, confirming disease-causing variants remains challenging. We applied a gene ... ...

Abstract	The application of whole-exome sequencing has led to the identification of high- and moderate-risk variants that contribute to cutaneous melanoma susceptibility. However, confirming disease-causing variants remains challenging. We applied a gene coexpression network analysis to prioritize the candidate genes identified from whole-exome sequencing of 34 melanoma-prone families, with at least three affected members sequenced per family (N = 119 cases). A coexpression network was constructed from genotype-tissue expression project, skin melanoma from the cancer genome atlas, and primary melanocyte cultures. We performed module-specific enrichment and focused on modules associated with pigmentation processes because they are the best-studied and most well-known risk factors for melanoma susceptibility. We found that pigmentation-associated modules across the four expression datasets examined were enriched for well-known melanoma susceptibility genes plus genes associated with pigmentation. We also used network properties to prioritize genes within pigmentation modules as candidate susceptibility genes. Integrating information from coexpression network analysis and variant prioritization, we identified 36 genes (such as DCT, TPCN2, TRPM1, ATP10A, and EPHA5) as potential melanoma risk genes in the families. Our approach also allowed us to link families with private gene mutations on the basis of gene coexpression patterns and thereby may provide an innovative perspective in gene identification in high-risk families.
MeSH term(s)	Exome/genetics ; Genetic Predisposition to Disease ; Humans ; Melanoma/genetics ; Skin Neoplasms/genetics ; Exome Sequencing ; Melanoma, Cutaneous Malignant
Language	English
Publishing date	2022-02-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2022.01.029
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Article ; Online: Oral microbiome and risk of incident head and neck cancer: A nested case-control study.

Oral oncology

2023 Volume 137, Page(s) 106305

Abstract: Objectives: 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).: Materials and methods: 56 incident HNC cases were ... ...

Abstract	Objectives: 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). Materials and methods: 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. Results: 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). Conclusion: 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.
MeSH term(s)	Humans ; Case-Control Studies ; Head and Neck Neoplasms/epidemiology ; Microbiota ; Diet ; Porphyromonas gingivalis
Language	English
Publishing date	2023-01-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	1120465-5
ISSN	1879-0593 ; 0964-1955 ; 1368-8375
ISSN (online)	1879-0593
ISSN	0964-1955 ; 1368-8375
DOI	10.1016/j.oraloncology.2022.106305
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