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Association between risk of oral precancer and genetic variations in microRNA and related processing genes
Roshni Roy, Navonil De Sarkar, Sandip Ghose
1Human Genetics Unit, Indian Statistical Institute, 203, B,T, Road, Kolkata 700108, India. broy@isical.ac.in.
Background:
MicroRNAs have been implicated in cancer but studies on their role in precancer, such as leukoplakia, are limited. Sequence variations at eight miRNA and four miRNA processing genes were studied in 452 healthy controls and 299 leukoplakia patients to estimate risk of disease.
Results:
Genotyping by TaqMan assay followed by statistical analyses showed that variant genotypes at Gemin3 and mir-34b reduced risk of disease [OR = 0.5(0.3-0.9) and OR = 0.7(0.5-0.9) respectively] in overall patients as well as in smokers [OR = 0.58(0.3-1) and OR = 0.68(0.5-0.9) respectively]. Among chewers, only mir29a significantly increased risk of disease [OR = 1.8(1-3)]. Gene-environment interactions using MDR-pt program revealed that mir29a, mir34b, mir423 and Xpo5 modulated risk of disease (p < 0.002) which may be related to change in expression of these genes as observed by Real-Time PCR assays. But association between polymorphisms and gene expressions was not found in our sample set as well as in larger datasets from open access platforms like Genevar and 1000 Genome database.
Conclusion:
Variations in microRNAs and their processing genes modulated risk of precancer but further in-depth study is needed to understand mechanism of disease process.
Insights
Genetic variations in microRNAs (miRNAs) and their processing genes influence precancer risk. Specific miRNA polymorphisms, like Gemin3 and mir-34b, were found to reduce leukoplakia risk, particularly in smokers.
Area of Science:
- Genetics
- Molecular Biology
- Oncology
Background:
- MicroRNAs (miRNAs) are increasingly recognized for their role in cancer development.
- Research on miRNA involvement in precancerous conditions, such as leukoplakia, remains limited.
- This study investigates the association between genetic variations in miRNAs and their processing genes with leukoplakia risk.
Purpose of the Study:
- To evaluate the impact of sequence variations in eight miRNA genes and four miRNA processing genes on the risk of developing leukoplakia.
- To explore potential gene-environment interactions, specifically in relation to smoking and chewing habits.
- To investigate the correlation between genetic polymorphisms and gene expression levels.
Main Methods:
- Genotyping of 452 healthy controls and 299 leukoplakia patients using TaqMan assays.
- Statistical analyses, including logistic regression and the MDR-pt program for gene-environment interactions.
- Real-Time PCR assays to assess gene expression, with validation using Genevar and 1000 Genome databases.
Main Results:
- Variant genotypes in Gemin3 and mir-34b were associated with a reduced risk of leukoplakia (OR=0.5 and OR=0.7, respectively).
- These protective effects were also observed in smokers.
- In chewers, mir29a polymorphism significantly increased disease risk (OR=1.8), while gene-environment interactions involving mir29a, mir34b, mir423, and Xpo5 modulated risk.
- No significant association was found between polymorphisms and gene expression levels in the studied datasets.
Conclusions:
- Sequence variations in microRNAs and their processing genes can modulate the risk of precancer.
- Further research is required to elucidate the precise mechanisms underlying these genetic influences on disease progression.
- Understanding these genetic factors may offer insights into early detection and prevention strategies for leukoplakia.
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