Page 88 - SRPSKO DRUŠTVO ISTRAŽIVAČA RAKA

Serbian Association for Cancer Research SDIRSACR

by the substance, which then affects multiple organs. A number of epidemiological studies have been conducted in
an attempt to ascertain whether there is an association between occupational and dietary exposure to acrylamide
and the incidence of cancer. However, the results of these studies have not indicated any such association. A number
of studies have demonstrated a correlation between acrylamide intake and the occurrence of cancers in renal cells,
the endometrium, and the ovary. In conclusion, while acrylamide has demonstrated carcinogenic potential in animal
models, current human studies provide limited and inconclusive evidence regarding its role in cancer development.
Further research, particularly studies utilizing biomarkers of exposure and accounting for genetic and lifestyle factors,
is necessary to clarify the potential health risks of dietary acrylamide.

Acknowledgments and funding: I would like to thank the Scientific Reserach Projects at Giresun University

L28

The role of microbiota in urinary bladder cancer

Janoš Terzić1

1 Laboratory for Cancer Research, University of Split, School of Medicine, Croatia

Keywords: microbiota, carcinogens, bladder neoplasms

Exposure to environmental pollutants and the composition of the human microbiome are increasingly recognized
as significant factors predisposing individuals to tumor development. While the biotransformation of xenobiotics,
including pollutants, by human-associated microorganisms has been shown to influence toxicokinetics and tissue
exposure to these compounds, the impact of such microbial activity on chemical-induced carcinogenesis remains
inadequately understood. Our research demonstrates that depletion of the gut microbiota significantly alters the
toxicokinetics of nitrosamines, resulting in reduced incidence and severity of nitrosamine-induced urinary bladder
cancer in mice. By employing both in vitro and in vivo methodologies, including individualized human gut bacterial
cultures and gnotobiotic mouse models, we causally linked gut bacterial biotransformation of nitrosamines to
carcinogen metabolism. Importantly, we found that this metabolic activity varies among individuals according to their
specific microbial profiles and is relevant across structurally related nitrosamine carcinogens. These findings indicate
that the gut microbiota’s metabolic capacity may be a critical, yet previously underappreciated, modifier of risk for
chemical-induced cancer, offering new possibilities for microbiome-targeted risk assessment and preventive strategies.
Building on this foundation, we investigated the urinary microbiome in bladder cancer by analyzing urine samples
from bladder cancer patients and healthy controls using 16S rRNA sequencing. Firmicutes were the most abundant
phylum across groups, and while overall composition and diversity did not differ significantly, specific operational
taxonomic units (OTUs) varied: Fusobacterium nucleatum, a genus linked to protumorigenic activity, was enriched
in cancer patients. In contrast, OTUs corresponding to Veillonella, Streptococcus, and Corynebacterium were more
prevalent among healthy controls. Lastly, we examined the dynamics of urinary microbiota during BCG immunotherapy
for high-risk non-muscle-invasive bladder cancer. Microbiome composition changed throughout treatment, and
differences between responders and non-responders were observed pre-therapy, specifically, higher Aureispira and
lower Negativicoccus succinivorans in non-responders.
Collectively, these findings highlight the active role of urinary microbiota in bladder cancer pathogenesis and treatment
and underscore the need for further research into microbiome-based biomarkers and intervention strategies.

73