Breast tissue, oral and urinary microbiomes in breast cancer
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Hannah Wang1,2, Jessica Altemus1, Farshad Niazi1, Holly Green4, Benjamin C. Calhoun5, Charles Sturgis5, Stephen R. Grobmyer2,4,6,8 and Charis Eng1,2,3,7,8
1Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
2Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, Cleveland, OH, USA
3Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA
4Surgical Oncology, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
5Department of Anatomic Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA
6Comprehensive Breast Cancer Program, Cleveland Clinic, Cleveland, OH, USA
7Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA
8Germline High Risk Focus Group, CASE Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA
Charis Eng, email: [email protected]
Stephen R. Grobmyer, email: [email protected]
Keywords: microbiome, metagenomics, breast cancer, oral, urine
Received: June 05, 2017 Accepted: July 09, 2017 Published: August 14, 2017
It has long been proposed that the gut microbiome contributes to breast carcinogenesis by modifying systemic estrogen levels. This is often cited as a possible mechanism linking breast cancer and high-fat, low-fiber diets as well as antibiotic exposure, associations previously identified in population-based studies. More recently, a distinct microbiome has been identified within breast milk and tissue, but few studies have characterized differences in the breast tissue microbiota of patients with and without cancer, and none have investigated distant body-site microbiomes outside of the gut. We hypothesize that cancerous breast tissue is associated with a microbiomic profile distinct from that of benign breast tissue, and that microbiomes of more distant sites, the oral cavity and urinary tract, will reflect dysbiosis as well. Fifty-seven women with invasive breast cancer undergoing mastectomy and 21 healthy women undergoing cosmetic breast surgery were enrolled. The bacterial 16S rRNA gene was amplified from urine, oral rinse and surgically collected breast tissue, sequenced, and processed through a QIIME-based bioinformatics pipeline. Cancer patient breast tissue microbiomes clustered significantly differently from non-cancer patients (p=0.03), largely driven by decreased relative abundance of Methylobacterium in cancer patients (median 0.10 vs. 0.24, p=0.03). There were no significant differences in oral rinse samples. Differences in urinary microbiomes were largely explained by menopausal status, with peri/postmenopausal women showing decreased levels of Lactobacillus. Independent of menopausal status, however, cancer patients had increased levels of gram-positive organisms including Corynebacterium (p<0.01), Staphylococcus (p=0.02), Actinomyces (p<0.01), and Propionibacteriaceae (p<0.01). Our observations suggest that the local breast microbiota differ in patients with and without breast cancer. Cancer patient urinary microbiomes were characterized by increased levels of gram-positive organisms in this study, but need to be further studied in larger cohorts.
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