Investigation of the association between the fecal microbiota and breast cancer in postmenopausal women: a population-based case-control pilot study

Abstract

We investigated whether the gut microbiota differed in 48 postmenopausal breast cancer case patients, pretreatment, vs 48 control patients. Microbiota profiles in fecal DNA were determined by Illumina sequencing and taxonomy of 16S rRNA genes. Estrogens were quantified in urine. Case-control comparisons employed linear and unconditional logistic regression of microbiota α-diversity (PD_whole tree) and UniFrac analysis of β-diversity, with two-sided statistical tests. Total estrogens correlated with α-diversity in control patients (Spearman Rho = 0.37, P = .009) but not case patients (Spearman Rho = 0.04, P = .77). Compared with control patients, case patients had statistically significantly altered microbiota composition (β-diversity, P = .006) and lower α-diversity (P = .004). Adjusted for estrogens and other covariates, odds ratio of cancer was 0.50 (95% confidence interval = 0.30 to 0.85) per α-diversity tertile. Differences in specific taxa were not statistically significant when adjusted for multiple comparisons. This pilot study shows that postmenopausal women with breast cancer have altered composition and estrogen-independent low diversity of their gut microbiota. Whether these affect breast cancer risk and prognosis is unknown.

Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Figures

Figure 1.

Fecal microbiota differences between postmenopausal breast cancer case patients and control patients. A) Odds ratio (square) and 95% confidence interval (bar) of breast cancer by tertile of alpha diversity (phylogenetic diversity [PD]_whole tree). Odds ratios by tertile are presented. B) Beta diversity, quantile-quantile plot of two-sided Wilcoxon rank-sum P values for all genus-level taxa. The distribution (x-axis expected, y-axis observed) diverges from the null (diagonal line) for many taxa. C) Beta diversity, distribution of the first principal coordinate values (PC1, 11.5% of the variance*) of the unweighted UniFrac distance matrix. Boxes are the interquartile range; median values are bands within the boxes; whiskers are 1.5-times the IQR; open circle is an outlier value. CI = confidence interval; PD = phylogenetic diversity.