The Human Microbiome in Relation to Cancer Risk: A Systematic Review of Epidemiologic Studies

Abstract

The microbiome has been hypothesized to play a role in cancer development. Because of the diversity of published data, an overview of available epidemiologic evidence linking the microbiome with cancer is now needed. We conducted a systematic review using a tailored search strategy in Medline and EMBASE databases to identify and summarize the current epidemiologic literature on the relationship between the microbiome and different cancer outcomes published until December 2019. We identified 124 eligible articles. The large diversity of parameters used to describe microbial composition made it impossible to harmonize the different studies in a way that would allow metaanalysis, therefore only a qualitative description of results could be performed. Fifty studies reported differences in the gut microbiome between patients with colorectal cancer and various control groups. The most consistent findings were for Fusobacterium, Porphyromonas, and Peptostreptococcus being significantly enriched in fecal and mucosal samples from patients with colorectal cancer. For the oral microbiome, significantly increased and decreased abundance was reported for Fusobacterium and Streptococcus, respectively, in patients with oral cancer compared with controls. Overall, although there was a large amount of evidence for some of these alterations, most require validation in high-quality, preferably prospective, epidemiologic studies.

Tumor-Associated Microbiome: Where Do We Stand?

“…Bacteria, viruses, and other micro-organisms located in different body compartments have been correlated with increased susceptibility of developing different cancers [ 19 , 20 , 21 , 22 ]. Cancer patients seem to harbor a specific microbiome composition in the tumor niche and also within the tumor’s body compartment, which differs from healthy controls [ 23 , 24 , 25 , 26 ].…”

“…In lung cancer , many studies have consistently reported different bacterial communities in the lung tissue of patients with lung cancer when compared to healthy individuals [ 22 , 106 , 107 ]. A meta-analysis of epidemiologic studies analyzed previous lung infections as risk factors for lung cancer.…”

“…A recent report from the International Agency for Cancer Research points out a high degree of heterogeneity across microbiome studies in terms of method of description, techniques used, taxonomic deepness, and lack of information about confounding factors [ 22 ]. There is an urge for standardization of methodology and result-reporting as well as for bias control in microbiome-related studies.…”

“…Studies that utilize normal tissue obtained from national tissue banks or local tissue donor programs might be useful in giving a general overview of microbiome composition in individuals free of cancer, but caution should be exercised when interpreting differences with tumor tissues since tissue-bank or donor normal tissues may differ in other important ways such as age, overall health status, and other variables. The study of case–control differences in oral or gut microbiome composition from saliva or stool samples as proxies for tissue microbiomes or as risk factors themselves (e.g., via systemic effects on inflammation) has been considered in the majority of epidemiological studies of microbiome composition as a potential risk factor for cancer [ 22 ].…”

Bacterial, Archaea, and Viral Transcripts (BAVT) Expression in Gynecological Cancers and Correlation with Regulatory Regions of the Genome

“…A subset of these viruses are known to integrate into the human genome [ 2 ]. H. pylori association with carcinogenesis is one of the best understood [ 3 ], but there are also other microbes that have been associated with cancer [ 4 ], including bladder [ 5 ], and colon [ 6 , 7 , 8 ]. Some of these bacteria associated with cancer may alter the microenvironment to favor tumor formation or favor certain alterations in specific cancers [ 3 ].…”