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Type 2 Diabetes-Related Variants Influence the Risk of Developing Prostate Cancer: A Population-Based Case-Control
José Manuel Sánchez-Maldonado1,2,3, Ricardo Collado4, Antonio José Cabrera-Serrano1,2,3
1Genomic Oncology Area, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government, PTS Granada, 18016 Granada, Spain.
Cancers
|May 28, 2022
Summary
Common variants for type 2 diabetes (T2D) significantly decrease prostate cancer (PCa) risk, particularly involving the HNF1B gene. These T2D variants may influence PCa risk through immune responses and gene expression.
Area of Science:
- Genetics
- Oncology
- Immunology
Background:
- Type 2 Diabetes (T2D) and prostate cancer (PCa) are common diseases with complex genetic components.
- Genome-wide association studies (GWAS) have identified numerous genetic variants associated with T2D risk.
- The potential overlap in genetic risk factors between T2D and PCa remains an area of active investigation.
Purpose of the Study:
- To investigate whether common variants identified for T2D risk influence the risk of developing PCa.
- To explore the potential role of these T2D-associated variants in modulating host immune responses.
- To validate the association of selected single nucleotide polymorphisms (SNPs) with PCa risk through meta-analysis.
Main Methods:
- GWAS data from 304 PCa patients and 686 controls were analyzed.
- Meta-analysis was performed combining study data with UKBiobank, FinnGen, and published cohorts.
- Correlations with immune cell populations, protein levels, and cytokine responses were assessed.
- Expression quantitative trait loci (eQTL) analysis was conducted.
Main Results:
- Meta-analysis confirmed that specific T2D SNPs (FTO, HNF1B, JAZF1) significantly decrease PCa risk.
- NOTCH2 and RBMS1 SNPs showed a non-statistically significant association with PCa risk.
- The protective effect of HNF1B variants may be mediated by the SULT1A1 protein.
- eQTL analysis indicated that T2D SNPs influence PCa risk by modulating gene mRNA levels in blood and/or liver.
Conclusions:
- Functional T2D-related variants demonstrably influence prostate cancer risk.
- The findings suggest a potential link between T2D genetic factors and PCa development, possibly mediated by immune pathways.
- Further research is needed to validate these functional results in tumoral tissue contexts.
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