Evaluation of biomarkers, genetic mutations, and epigenetic modifications in early diagnosis of pancreatic cancer

BACKGROUND Pancreatic cancer(PC)is one of the deadliest malignancies with an alarming mortality rate.Despite significant advancement in diagnostics and therapeutics,early diagnosis remains elusive causing poor prognosis,marred by mutations and epigenetic modifications in key genes which contribute to disease progression.AIM To evaluate the various biological tumor markers collectively for early diagnosis which could act as prognostic biomarkers and helps in future therapeutics of PC in Kashmir valley.METHODS A total of 50 confirmed PC cases were included in the study to evaluate the levels of carbohydrate antigen 19-9(CA 19-9),tissue polypeptide specific antigen(TPS),carcinoembryonic antigen(CEA),vascular endothelial growth factor-A(VEGF-A),and epidermal growth factor receptor(EGFR).Mutational analysis was performed to evaluate the mutations in Kirsten rat sarcoma(KRAS),Breast cancer type 2(BRCA-2),and deleted in pancreatic cancer-4(DPC-4)genes.However,epigenetic modifications(methylation of CpG islands)were performed in the promoter regions of cyclin-dependent kinase inhibitor 2A(p16;CDKN2A),MutL homolog 1(hMLH1),and Ras association domain-containing protein 1(RASSF1A)genes.RESULTS We found significantly elevated levels of biological markers CA 19-9(P≤0.05),TPS(P≤0.05),CEA(P≤0.001),and VEGF(P≤0.001).Molecular genetic analysis revealed that KRAS gene mutation is predominant in codon 12(16 subjects,P≤0.05),and 13(12 subjects,P≤0.05).However,we did not find a mutation in DPC-4(1203G>T)and BRCA-2(617delT)genes.Furthermore,epigenetic modification revealed that CpG methylation in 21(P≤0.05)and 4 subjects in the promoter regions of the p16 and hMLH1 gene,respectively.CONCLUSION In conclusion,CA 19-9,TPS,CEA,and VEGF levels were significantly elevated and collectively have potential as diagnostic and prognostic markers in PC.Global data of mutation in the KRAS gene commonly in codon 12 and rare in codon 13 could augment the predisposition towards PC.Additionally,methylation of the p16 gene could also modulate transcription of genes thereby increasing the predisposition and susceptibility towards PC.

Newly identified genetic variant rs2294693 in UNC5CL gene is associated with decreased risk of esophageal carcinoma in the J&K Population–India

Esophageal cancer is the second most common type of cancer after lung carcinoma in the state of Jammu and Kashmir(J&K).The understanding of genetics in Esophageal cancer development is poor in the state.Genome wide association studies(GWAS)has proved to be unsurpassed tool in identification of new loci associated with different cancers.GWAS in Chinese population has identified SNP rs2294693 present in UNC5CL(UNC-5 Family C-Terminal like)to be associated with non-cardia gastric cancer.We performed a case control association study and genotyped the SNP rs2294693 using Taqman allele discrimination assay in 566 individuals(166 esophageal cancer patients and 400 controls)belonging to the J&K population.A statistically significant protective association with allelic odds ratio of 0.73(0.56–0.94 at 95%CI)and p value=0.016 was observed.This is the first study in relation to esophageal cancer in the Jammu and Kashmir population,so far it has been studied in association with gastric carcinoma in the Chinese population only.The results indicate that the polymorphism rs2294693 is associated with esophageal cancer susceptibility and the mutant(T)allele might be a protective factor for esophageal cancer among Jammu and Kashmir population.Further the functional characterization of the variation is also warranted.