Associations between DNMT1 Gene Polymorphisms and Cancer Susceptibility: A Systematic Review and Meta-analysis

Area of Science:

• Genetics and Epigenetics
• Cancer Biology
• Molecular Epidemiology

Background:

• Aberrant DNA methylation is a hallmark of cancer cells, involving epigenetic alterations.
• DNA methyltransferase 1 (DNMT1) is a key enzyme in DNA methylation and a potential cancer susceptibility gene.
• Previous studies on DNMT1 polymorphisms and cancer risk have yielded inconsistent results.

Purpose of the Study:

• To clarify the relationship between DNMT1 polymorphisms and cancer susceptibility through a comprehensive meta-analysis.
• To consolidate existing evidence and provide a clearer understanding of DNMT1's role in cancer risk.

Main Methods:

• Systematic literature search of PubMed, Web of Science, and Scopus databases up to January 2025.
• Inclusion of 23 case-control studies examining 23 DNMT1 polymorphisms and cancer risk.
• Meta-analysis using fixed-effects or random-effects models to calculate odds ratios (OR) and 95% confidence intervals (CI), with heterogeneity and publication bias assessed.

Main Results:

• The meta-analysis included 23 case-control studies investigating 23 DNMT1 polymorphisms.
• Significant associations were found for rs2228612 (co-dominant model) and rs2228611 (dominant model) with overall cancer risk.
• Subgroup analyses indicated associations between rs2228612 and gastrointestinal cancer, and rs2228611 and breast cancer.

Conclusions:

• DNMT1 polymorphisms play a role in cancer susceptibility.
• Specific polymorphisms, rs2228612 and rs2228611, are notably associated with increased risk for certain cancers.
• Further high-quality research is warranted to validate these findings and elucidate the precise mechanisms.