Evaluation of Diagnostic and Prognostic Relevance of Single Nucleotide Polymorphism at let-7 micro RNA-binding site of KRAS3 /UTR in Oral Squamous Cell Carcinoma

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Professor, Consultant Pathologist, American Board Certified Pathologist, Fellow College of American Pathologists. Areas of interest Fine Needle Aspiration Cytology, Cytology, Cancer, Ethics, Islam, Humanity

Evaluation of Diagnostic and Prognostic Relevance of Single Nucleotide Polymorphism at let-7 micro RNA-binding site of KRAS3 /UTR in Oral Squamous Cell Carcinoma

1Nosheen Mahmood, 2Shamim Mushtaq,3 Qamar Jamal,4Muhammad Hanif, 5Humera Akhlaq and       6Rashid Awan

1Department of Pathology Ziauddin University, Karachi Pakistan,2Associate Professor, Biochemistry, Ziauddin University, 3Professor of Pathology, Ziauddin University, 4Head of department (Pr. Scientist) Clinical labs & Molecular biology Lab, Karachi Institute of Radiotherapy and Nuclear Medicine (KIRAN) Karachi, Pakistan, 5Assistant Professor Pathology, Jinnah Sind Medical University, 6Registrar Physician, Chinniot General Hospital

ABSTRACT

Objective: Asingle nucleotide polymorphism at Let 7 miRNA binding site in 3/ UTR of KRAS, creates a variant allele KRAS -LCS6 observed to impart poor prognosis in oral cancers. Objective of this study was to explore diagnostic and prognostic relevance of KRAS-LCS6 variant allele in oral squamous cell cancer.

Methods: Study was conducted on a total of 100 cases and 100 age and sex matched healthy controls after taking informed written consent. Proposal was approved by Institutional Review Board of Ziauddin University. KRAS–LCS6 SNP genotyping was done via Taqman allelic discrimination assay using allele specific primers and probes ordered from macrogen on real time PCR instrument.

Results:Mean age at presentation was 45.12 ± 12.42   for cases and 44.22 ±12.2 for controls p>0.05. Male to female ratio among cases was 2.2:1. Majority (70%) of cases had a moderate differentiation, and nodal metastasis (96 %). KRAS-LCS 6 variant allele resulting from a single nucleotide polymorphism at Let 7 miRNA binding was observed only in 4 patients and none of the healthy controls. All 4 subjects had a heterozygous genotype (TG) with homozygous genotype (GG) observed in none of the cases or controls.

Conclusion: The variant allele does not exist in this cohort of patients and hence KRAS   LCS6 SNP genotyping is not an ideal marker for early detection or predicting disease outcome in our patients with oral cancer.



         

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