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.

Abstract

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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