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The let-7 microRNA binding site variant in KRAS as a predictive biomarker for head and neck cancer patients with
Murat Ulusan1, Sena Sen2, Rasim Yilmazer1
1Department of Otorhinolaryngology-Head and Neck Surgery, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye.
Background:
The let-7 family of microRNAs regulate multiple oncogenes including the KRAS gene and has been shown to play a critical role in carcinogenesis. In this study, we aimed to investigate polymorphic alterations of the let-7 miRNA binding site (rs61764370) in the 3'UTR region of the KRAS gene as a predictive biomarker for head and neck cancer (HNC) and to evaluate its association with clinicopathological parameters.
Material And Methods:
The frequency of the KRAS-LCS6 variant in 216 Turkish HNC' patients and 85 healthy individuals were evaluated. After extracting DNA from whole blood, the variant allele was analyzed by polymerase chain reaction and restriction fragment length polymorphism method. Genotype and allele frequencies were evaluated using the De-Finetti case-control program.
Results:
85.6 % of the patients were wild type, 13 % heterozygous and 1.4 % homozygous variant. Although the KRAS-LCS6 variant was not associated with the risk of HNC (p > 0.05), G homozygous variant allele was found to be significantly associated with HNC patients having lymph node metastasis [T vs G: OR(%95 CI)= 2.370 (1.03-5.41), p = 0.03, χ2 = 4.38]. It was found statistical significance between genotype frequencies and smoker patients [TT vs TG: OR(%95 CI)= 0.357 (0.13-0.97), p = 0.03, χ2 = 4.32] by using De-Finetti analysis. Statistical significance was observed between KRAS-LCS6 genotype frequencies and gender, smoking, alcohol, early/late-stage, lymph node metastasis according to univariate analysis and Cox proportional hazards regression model (p < 0.05).
Conclusion:
This is the first study to reveal the relationship between KRAS-LCS6 variant and lymph node metastasis in HNC. The LCS6 variant of the KRAS gene may be a candidate predictor risk biomarker for lymph node metastasis in HNC.
Insights
The KRAS-LCS6 variant, a let-7 miRNA binding site polymorphism, is not linked to head and neck cancer (HNC) risk. However, this variant may predict lymph node metastasis in HNC patients.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- The let-7 miRNA family regulates oncogenes like KRAS, impacting carcinogenesis.
- Polymorphic variations in miRNA binding sites can influence cancer development and progression.
Purpose of the Study:
- To investigate the KRAS-LCS6 variant (rs61764370) in the 3'UTR of the KRAS gene.
- To assess its potential as a predictive biomarker for head and neck cancer (HNC).
- To evaluate associations between the KRAS-LCS6 variant and HNC clinicopathological parameters.
Main Methods:
- Genotyping of the KRAS-LCS6 variant in 216 Turkish HNC patients and 85 healthy controls.
- DNA extraction from whole blood followed by polymerase chain reaction and restriction fragment length polymorphism analysis.
- Evaluation of genotype and allele frequencies using De-Finetti case-control program and univariate/Cox regression analyses.
Main Results:
- The KRAS-LCS6 variant was not associated with overall HNC risk (p > 0.05).
- The homozygous variant allele showed a significant association with lymph node metastasis in HNC patients (OR=2.370, p=0.03).
- Genotype frequencies were significantly associated with gender, smoking status, alcohol consumption, disease stage, and lymph node metastasis (p < 0.05).
Conclusions:
- This study is the first to demonstrate a link between the KRAS-LCS6 variant and lymph node metastasis in HNC.
- The KRAS-LCS6 variant may serve as a potential predictive biomarker for lymph node metastasis in head and neck cancer.
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