Levels of 5α-reductase gene in intestinal lavage fluid decrease with progression of colorectal cancer

Area of Science:

• Microbiology
• Gastroenterology
• Oncology

Background:

• Colorectal cancer (CRC) is a major cause of cancer mortality, with links to intestinal microbiota and bile acid metabolism.
• Secondary bile acids are implicated in CRC risk, while isoallolithocholic acid (isoalloLCA) may offer protective benefits.
• The 5α-reductase gene (5ar) is involved in isoalloLCA biosynthesis, and its intestinal levels are measurable.

Purpose of the Study:

• To investigate the association between intestinal 5ar levels and CRC.
• To compare 5ar levels across the adenoma-carcinoma sequence.
• To explore novel strategies for CRC risk monitoring.

Main Methods:

• DNA extraction from intestinal lavage fluids (ILF) from 144 colonoscopies.
• Next-generation sequencing (NGS) to analyze 5ar homolog sequences.
• Quantitative PCR (qPCR) to measure 5ar levels in all samples.

Main Results:

• Analysis of 292,042 NGS-derived 5ar sequences identified prevalent variants linked to specific gut bacteria.
• qPCR revealed significantly lower intestinal 5ar levels in the CRC group compared to non-neoplastic mucosa (P = 0.0004).
• A trend of decreasing 5ar levels was observed from non-neoplastic mucosa to adenoma and carcinoma stages.

Conclusions:

• Intestinal 5ar levels are associated with CRC progression.
• PCR-based monitoring of 5ar levels in intestinal samples may serve as a non-invasive, rapid, and cost-effective CRC risk assessment tool.