Gut microbiome associations with breast cancer risk factors and tumor characteristics: a pilot study

From BugSigDB
Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Wu AH, Tseng C, Vigen C, Yu Y, Cozen W, Garcia AA, Spicer D
Journal
Breast cancer research and treatment
Year
2020
Keywords:
Age at menarche, HER2 status, Microbiome, Tumor characteristics
OBJECTIVE: To investigate the association between gut microbiome with breast tumor characteristics (receptor status, stage and grade) and known breast cancer risk factors. METHODS: In a pilot cross-sectional study of 37 incident breast cancer patients, fecal samples collected prior to chemotherapy were analyzed by 16S ribosomal RNA (rRNA) gene-based sequencing protocol. Alpha diversity and specific taxa by tumor characteristics and breast cancer risk factors were tested by Wilcoxon rank sum test, and by differential abundance analysis, using a zero-inflated negative binomial regression model with adjustment for total counts, age and race/ethnicity. RESULTS: There were no significant alpha diversity or phyla differences by estrogen/progesterone receptor status, tumor grade, stage, parity and body mass index. However, women with human epidermal growth factor receptor 2 positive (HER2+) (n = 12) compared to HER2- (n = 25) breast cancer showed 12-23% lower alpha diversity [number of species (OTU) p = 0.033, Shannon index p = 0.034], lower abundance of Firmicutes (p = 0.005) and higher abundance of Bacteroidetes (p = 0.089). Early menarche (ages ≤ 11) (n = 11) compared with later menarche (ages ≥ 12) (n = 26) was associated with lower OTU (p = 0.036), Chao1 index (p = 0.020) and lower abundance of Firmicutes (p = 0.048). High total body fat (TBF) (> 46%) (n = 12) compared to lower (≤ 46%) TBF was also associated with lower Chao 1 index (p = 0.011). There were other significant taxa abundance differences by HER2 status, menarche age, as well as other tumor and breast cancer risk factors. CONCLUSIONS AND RELEVANCE: Further studies are needed to identify characteristics of the human microbiome and the interrelationships between breast cancer hormone receptor status and established breast cancer risk factors.

Experiment 1


Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/06/21

Curator: Itslanapark

Revision editor(s): WikiWorks, LGeistlinger, Claregrieve1, Itslanapark, Peace Sandy

Subjects

Location of subjects
United States of America
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
HER2 Positive Breast Carcinoma ERBB2 Overexpressing subtype of breast carcinoma,HER2 Overexpressing breast carcinoma,HER2 Overexpressing subtype of breast carcinoma,HER2 Positive breast cancer,HER2 positive breast carcinoma,Her2-receptor positive breast cancer,HER2 Positive Breast Carcinoma,hER2 Positive Breast Carcinoma
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Her2 negative tumor
Group 1 name Corresponds to the case (exposed) group for case-control studies
Her2 positive tumor
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Breast cancer patients with Her2 positive tumors (human epidermal growth factor receptive 2 positive)
Group 0 sample size Number of subjects in the control (unexposed) group
25
Group 1 sample size Number of subjects in the case (exposed) group
12
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Antibiotic use one week or more during the month prior to fecal sample collection.

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
Mann-Whitney (Wilcoxon)
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.001
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, ethnic group, race, Confounders controlled for: "total counts" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.total counts

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/06/29

Curator: Itslanapark

Revision editor(s): Itslanapark

Source: Table 3

Description: Mean ratio estimates found using zero-inflated negative binomial model of taxa abundance by HER2 status

Abundance in Group 1: increased abundance in Her2 positive tumor

NCBI Quality ControlLinks
Acidaminococcus

Revision editor(s): Itslanapark

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/06/30

Curator: Itslanapark

Revision editor(s): Itslanapark, Claregrieve1

Source: Table 3

Description: Mean ratio estimates found using zero-inflated negative binomial model of taxa abundance by ER, PR, and HER2 status

Abundance in Group 1: decreased abundance in Her2 positive tumor

NCBI Quality ControlLinks
Desulfovibrio
Ruminococcus
Christensenellaceae

Revision editor(s): Itslanapark, Claregrieve1

Experiment 2


Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/07/05

Curator: Itslanapark

Revision editor(s): WikiWorks, LGeistlinger, Itslanapark, Victoria

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Age at menarche Age at menarche,age at menarche
Group 0 name Corresponds to the control (unexposed) group for case-control studies
early age at menarche (≤11)
Group 1 name Corresponds to the case (exposed) group for case-control studies
later age at menarche (≥12)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
breast cancer patients with age at menarche being over 12 years old
Group 0 sample size Number of subjects in the control (unexposed) group
11
Group 1 sample size Number of subjects in the case (exposed) group
26

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
increased

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/07/07

Curator: Itslanapark

Revision editor(s): Itslanapark, Claregrieve1

Source: Table 5

Description: Mean estimate ratios gound using a zero-inflated negative binomial model of taxa abundances by age group, menarche age and parity.

Abundance in Group 1: increased abundance in later age at menarche (≥12)

NCBI Quality ControlLinks
Escherichia

Revision editor(s): Itslanapark, Claregrieve1

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/07/07

Curator: Itslanapark

Revision editor(s): Itslanapark

Source: Table 5

Description: Mean estimate ratios found using a zero-inflated negative binomial model of taxa abundances by age group, menarche age and parity.

Abundance in Group 1: decreased abundance in later age at menarche (≥12)

NCBI Quality ControlLinks
Methanobrevibacter
Ruminococcus

Revision editor(s): Itslanapark

Experiment 3


Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/07/05

Curator: Itslanapark

Revision editor(s): WikiWorks, LGeistlinger, Itslanapark, Victoria

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Estrogen receptor status Estrogen receptor status,estrogen receptor status
Group 0 name Corresponds to the control (unexposed) group for case-control studies
ER+
Group 1 name Corresponds to the case (exposed) group for case-control studies
ER-
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
breast cancer patients with negative Estrogen Receptor status
Group 0 sample size Number of subjects in the control (unexposed) group
9
Group 1 sample size Number of subjects in the case (exposed) group
28

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/07/05

Curator: Itslanapark

Revision editor(s): Itslanapark

Source: Table 3

Description: Mean ratio estimates obtained by zero-inflated negative binomial model of taxa abundances by estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status.

Abundance in Group 1: decreased abundance in ER-

NCBI Quality ControlLinks
Haemophilus
Veillonella

Revision editor(s): Itslanapark

Experiment 5


Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/07/07

Curator: Itslanapark

Revision editor(s): WikiWorks, LGeistlinger, Itslanapark, Victoria

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Breast cancer breast cancer,breast tumor,cancer of breast,malignant breast neoplasm,malignant breast tumor,malignant neoplasm of breast,malignant neoplasm of the breast,malignant tumor of breast,malignant tumor of the breast,mammary cancer,mammary neoplasm,mammary tumor,primary breast cancer,Breast cancer
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Grade Low (I/II)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Grade High (III)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
breast cancer patients with grade high level tumors (Grade III)
Group 0 sample size Number of subjects in the control (unexposed) group
14
Group 1 sample size Number of subjects in the case (exposed) group
23

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/07/07

Curator: Itslanapark

Revision editor(s): Itslanapark

Source: Table 4

Description: Mean estimate ratios found using zero- inflated negative binomial model of taxa abundances by grade and stage of breast cancer.

Abundance in Group 1: increased abundance in Grade High (III)

NCBI Quality ControlLinks
Eggerthella

Revision editor(s): Itslanapark

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/07/07

Curator: Itslanapark

Revision editor(s): Itslanapark

Source: Table 4

Description: Mean estimate ratios found using zero- inflated negative binomial model of taxa abundances by grade and stage of breast cancer.

Abundance in Group 1: decreased abundance in Grade High (III)

NCBI Quality ControlLinks
Lachnospiraceae
Anaerostipes

Revision editor(s): Itslanapark

Experiment 6


Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/07/07

Curator: Itslanapark

Revision editor(s): WikiWorks, Claregrieve1, Itslanapark, Victoria

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Breast cancer stage Breast cancer stage,breast cancer stage
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Stage Low (I/II)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Stage High (III)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Breast cancer patients with high stage progression of breast cancer (Stage III).
Group 0 sample size Number of subjects in the control (unexposed) group
22
Group 1 sample size Number of subjects in the case (exposed) group
15

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/07/07

Curator: Itslanapark

Revision editor(s): Itslanapark

Source: Table 4

Description: Mean estimate ratios found using zero- inflated negative binomial model of taxa abundances by grade and stage of breast cancer.

Abundance in Group 1: increased abundance in Stage High (III)

NCBI Quality ControlLinks
Clostridium
Veillonella
Haemophilus

Revision editor(s): Itslanapark

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/07/07

Curator: Itslanapark

Revision editor(s): Itslanapark

Source: Table 4

Description: Mean estimate ratios found using zero- inflated negative binomial model of taxa abundances by grade and stage of breast cancer.

Abundance in Group 1: decreased abundance in Stage High (III)

NCBI Quality ControlLinks
Acidaminococcus
Catenibacterium

Revision editor(s): Itslanapark

Experiment 7


Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/07/07

Curator: Itslanapark

Revision editor(s): WikiWorks, Claregrieve1, Itslanapark, Victoria

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Age Age,age
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Age 50+
Group 1 name Corresponds to the case (exposed) group for case-control studies
Age ≤50
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Breast cancer patients whose age is ≤50 years old.
Group 0 sample size Number of subjects in the control (unexposed) group
17
Group 1 sample size Number of subjects in the case (exposed) group
20

Lab analysis

Statistical Analysis

Statistical test
Kruskall-Wallis
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
ethnic group, race, Confounders controlled for: "total counts" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.total counts

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/07/07

Curator: Itslanapark

Revision editor(s): Itslanapark

Source: Table 5

Description: Mean estimate ratios found using a zero-inflated negative binomial model of taxa abundances by age group, menarche age and parity.

Abundance in Group 1: increased abundance in Age ≤50

NCBI Quality ControlLinks
Clostridiaceae
Clostridium
Enterobacteriaceae
Lactococcus

Revision editor(s): Itslanapark

Experiment 8


Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/07/07

Curator: Itslanapark

Revision editor(s): WikiWorks, Claregrieve1, Itslanapark, Victoria

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Parous Parous,parous
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Parous
Group 1 name Corresponds to the case (exposed) group for case-control studies
Nulliparous
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Breast cancer patients who are nulliparous (have had no live births.)
Group 0 sample size Number of subjects in the control (unexposed) group
29
Group 1 sample size Number of subjects in the case (exposed) group
8

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, ethnic group, race, Confounders controlled for: "total counts" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.total counts

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/07/07

Curator: Itslanapark

Revision editor(s): Itslanapark

Source: Table 5

Description: Mean estimate ratios found using a zero-inflated negative binomial model of taxa abundances by age group, menarche age and parity.

Abundance in Group 1: decreased abundance in Nulliparous

NCBI Quality ControlLinks
Catenibacterium

Revision editor(s): Itslanapark

Experiment 9


Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/07/07

Curator: Itslanapark

Revision editor(s): WikiWorks, Claregrieve1, Itslanapark, Victoria

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Body mass index BMI,Quetelet's Index,Body mass index,body mass index
Group 0 name Corresponds to the control (unexposed) group for case-control studies
BMI<25
Group 1 name Corresponds to the case (exposed) group for case-control studies
BMI≥25
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Breast cancer patients with a high body mass index (BMI≥25)
Group 0 sample size Number of subjects in the control (unexposed) group
9
Group 1 sample size Number of subjects in the case (exposed) group
28

Lab analysis

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/07/07

Curator: Itslanapark

Revision editor(s): Itslanapark

Source: Table 6

Description: Mean estimate ratios found using a zero-inflated negative binomial model of taxa abundances by BMI, total body fat, and physical activity.

Abundance in Group 1: increased abundance in BMI≥25

NCBI Quality ControlLinks
Akkermansia

Revision editor(s): Itslanapark

Experiment 10


Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/07/07

Curator: Itslanapark

Revision editor(s): WikiWorks, Claregrieve1, Itslanapark, Victoria

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Body fat percentage Body fat percentage,body fat percentage
Group 0 name Corresponds to the control (unexposed) group for case-control studies
TBF≤46%
Group 1 name Corresponds to the case (exposed) group for case-control studies
TBF>46%
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Breast cancer patients with a total body fat percentage ≥46%.
Group 0 sample size Number of subjects in the control (unexposed) group
25
Group 1 sample size Number of subjects in the case (exposed) group
12
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Not specified

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
Not specified

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
decreased

Signature 1

Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/07/07

Curator: Itslanapark

Revision editor(s): Itslanapark

Source: Table 6

Description: Mean estimate ratios found using a zero-inflated negative binomial model of taxa abundances by BMI, total body fat, and physical activity.

Abundance in Group 1: increased abundance in TBF>46%

NCBI Quality ControlLinks
Clostridiaceae

Revision editor(s): Itslanapark

Signature 2

Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/07/07

Curator: Itslanapark

Revision editor(s): Itslanapark

Source: Table 6

Description: Mean estimate ratios found using a zero-inflated negative binomial model of taxa abundances by BMI, total body fat, and physical activity.

Abundance in Group 1: decreased abundance in TBF>46%

NCBI Quality ControlLinks
Coriobacteriaceae

Revision editor(s): Itslanapark

Experiment 11


Reviewed Marked as Reviewed by Claregrieve1 on 2022/10/31

Curated date: 2021/07/08

Curator: Itslanapark

Revision editor(s): WikiWorks, Claregrieve1, Itslanapark, Victoria

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Physical activity Activities, Locomotor,Activities, Motor,Activities, Physical,Activity, Locomotor,Activity, Motor,Activity, Physical,Locomotor Activities,Locomotor Activity,Motor Activities,Motor Activity,Physical Activities,Physical activity,physical activity
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Yes Physical Activity
Group 1 name Corresponds to the case (exposed) group for case-control studies
No Physical Activity
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Breast cancer patients who do not have regular physical activity.
Group 0 sample size Number of subjects in the control (unexposed) group
24
Group 1 sample size Number of subjects in the case (exposed) group
13
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Antibiotic use one week or more during the month prior to fecal sample collection.

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, ethnic group, race, Confounders controlled for: "total counts" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.total counts

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
decreased