Abstract 751: Gut microbiome and breast cancer: Report from a case-control study in Vietnam

Abstract The importance of gut microbiome on human health is being increasingly recognized. The gut microbiota may play a critical role in breast cancer etiology, likely through the roles of the gut microbiota in estrogen and nutrient metabolism as well as in immune regulation. However, evidence on associations between breast cancer and gut microbiota is limited and inconsistent. Using resources from the Vietnamese Breast Cancer Case-Control Study (VBCS), we evaluated differences in gut microbiome profiles between women with breast cancer and healthy women. Pre-treatment tool samples of 162 incident breast cancer cases (age: 50.0±9.5) and stool samples of 370 age-matched controls (age: 49.7±9.0) were included in the study. The gut microbiome was measured using shotgun metagenomic sequencing. Differences in gut microbiome α-diversity and β-diversity between breast cancer patients and healthy controls were evaluated via linear regression models and PERMANOVA testing, respectively. Case-control differences in gut microbial taxa abundance were assessed through the differential abundance analysis with adjustment for potential confounders, including age, income levels, residence, menopausal status, reproductive factors, body mass index, comorbidity, dietary intake, and physical activity. An association with a false discovery rate (FDR) <0.1 was considered statistically significant. No significant difference between breast cancer patients and healthy controls was observed for α- and β-diversities. A total of 2,905 gut microbial taxa were evaluated. Among them, significant case-control differences were found in the abundance of one phylum, two classes, four orders, three families, four gena, and 67 species (all p<0.05 and FDR <0.1). Compared to healthy controls, breast cancer patients had a decreased abundance of species Pauljensenia keddieii, Bifidobacterium bifidum (phylum Actinobacteriota), Clostridium Q symbiosum, Faecalicatena fissicatena, Massilioclostridium methylpentosum, Parvimonas micra (phylum Firmicutes A), Leptotrichia wadei (phylum Fusobacteriota), Enterococcus D gallinarum, Lactobacillus H fermentum, Gemella haemolysans B, genus Streptococcus and its 24 species such as S. anginosus C, S. constellatus, S. equinus, S. infantis I, S. mitis, S. oralis, S. pseudopneumoniae O (phylum Firmicutes) (all p<0.05 and FDR <0.1). The species Clostridium Q symbiosum showed the strongest association, with a log2 fold-change (SE) of -2.02 (0.45), p=7.35 × 10−6; FDR=0.006. Additionally, breast cancer patients had an increased abundance of three species belonging to the phylum Firmicutes A including MGYG-HGUT-03165, MGYG-HGUT-04111, and MGYG-HGUT-00903, compared to healthy controls (p<0.05 and FDR <0.1). These results suggest that the gut microbiome of breast cancer differs from that of control women. Additional analyses are ongoing to reveal the biological underpinning of the observed associations. Citation Format: Sang Minh Nguyen, Huong T. Tran, Jirong Long, Martha J. Shrubsole, Hui Cai, Yaohua Yang, Thuan V. Tran, Wei Zheng, Xiao-Ou Shu. Gut microbiome and breast cancer: Report from a case-control study in Vietnam [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 751.