Screening the APC, MLH1, MSH2 and TP53 Mutations in Patients with Early Onset of Colorectal Cancer
- *Corresponding Author:
- Professor Leyla Djansugurova
Laboratory of Molecular Genetics
Institute of General Genetics and Cytology
Republic of Kazakhstan, Almaty, 050060
Al-Farabi ave, 93, Kazakhstan
E-mail: [email protected]
Received date: September 30, 2014; Accepted date: October 25, 2014; Published date: October 30, 2014
Citation: Djansugurova L, Zhunussova G, Khussainova E, Iksan O, Afonin G, et al. (2014) Screening the APC, MLH1, MSH2 and TP53 Mutations in Patients with Early Onset of Colorectal Cancer. J Carcinog Mutagen 5:197. doi: 10.4172/2157-2518.1000197
Copyright: © 2014 Djansugurova L, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: A molecular-genetic study of early onset colorectal cancer (CRC) patients in Kazakhstan.
Methods: The direct sequencing of crucial regions of key CRC genes (APC codons between nucleotides 967-1386 and 1286–1513; exons 8 and 16 of MLH1 and exon 7 of MSH2; exons 5-9 of TP53) was performed for early cancer-onset and suspected familial cases.
Results: Blood was collected from 249 patients diagnosed with rectal or colon cancer. There were 32 patients with early onset CRC (28-50 yrs), including 10 patients with a family history of cancer. Two types of nucleotide replacements were detected in intron 4 (c.376-19C>T) and intron 9 (c.993+12T>C) of TP53, both in the heterozygous state. Another nucleotide substitution was present in 15 patients in intron 15 of MLH1 (c.1732-90C>A) while known coding polymorphisms were observed in exon 8 of MLH1 (rs1799977-A655G/Ile219Val), in exon 7 of MSH2 (rs5028341-C1168T/Leu390Phe), in exon 15 of APC (rs1801166-G3949C/p.Glu1317Gln and rs41115–4479G>A). The single deletion, c.3613delA (p.Ser1205fs), located in exon 15 of APC gene, was found in the heterozygous state in two patients with a family history of adenomatous polyposis.
Conclusion: We suggest a possible role of MLH1 655A>G, MSH2 1168C>T, APC 4479G>A, and APC 3949G>C polymorphisms in the susceptibility to early onset of CRC. A single base pair deletion at codon 1205 (c.3613delA) of APC gene seems to be differentially associated with early-onset cases depending on having a family history of CRC.