Introduction Pancreatic cancer is one of the most common malignant tumours in the digestive tract in both sexes. Pancreatic adenocarcinoma shows the highest frequency of K-ras gene mutations among the common human cancers but the reasons are unknown. There is lack of knowledge of prevention, early diagnosis, and effective therapy. The molecular mechanism of pancreatic carcinogenesis remains to be fully explored from India. The study was designed to clarify the sensitivity and validity of K-ras point mutational analysis at codon 12 and codon 13 in North Indian patients with pancreatic diseases, and the possible correlation between the presence of mutation and histopathological findings.
Methods Sixty-five North Indian patients with pancreatic ductal adenocarcinoma, and fifty chronic pancreatitis were enrolled in this study. Out of 65 pancreatic cancer, 24 patients were female (36.92%) and 41 patients were male (63%) having an average age of 47.42±11.32 years (range 22–70 years), 50 chronic pancreatitis only seven were female (14%) and 43 were male (86%) having an average age of 36.02±10.55 years (range 20–63 years). Codon 12 K-ras mutations were examined using the two step polymerase chain reaction (PCR) with RFLP, followed single-strand conformation polymorphism (SSCP) and automated DNA sequencing.
Results The sensitivity of K-ras mutational analysis in surgically resected tissue samples of the pancreatic carcinoma was 72.30% (47/65) and mutations were found in 63% which was significantly higher than the chronic pancreatitis 33% (5/15) (P<0.01). The mutation pattern of K-ras codon 12 in pancreatic carcinoma 63% while it was 12% in chronic pancreatitis. The nucleotide sequences of K-ras showed the following transitions at codon12 GAG to GTG, GGC to GGG. The control group showed wild type GGA and GGC at codon12. It was also found that K-ras mutation rate was progressively increased from normal duct at the tumour-free resection margin to pancreatic carcinoma.
Conclusion Overall, our findings support the observations that K-ras mutations play a key role in dysregulated growth of pancreatic cancer and may explain at least in part the aggressive behaviour of this tumour type.
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