Significance of gene polymorphysm in development of colorectal cancer

Abstract

Aim. To determine the significance of polymorphism of MTHFR (Ala222Val), XPD (Lis751Gln), XRCC1 (Arg194Trp), XRCC1 (Arg399Gln), XRCC1 (Arg208His), APE1 (Asp148Glu), hOGG1 (ser326Ces), P53 (Pro47Ser), VEGF (C654G), EGFR(A2073T), TNF(G308A), CHEK2 (Ile157Thr), MMP1 (1607 1G>2G), TIMP1(C53CT) genes in development of colorectal cancer.

Materials and Methods. 106 Cases of colorectal cancer in patients who were on treatment in Ryazan Clinical Oncological Dispensary (Ryazan) were analyzed. Genotyping in all patients was performed using the method of isolation of DNA from leukocytes of venous blood with subsequent polymerase chain reaction (PCR) with electrophoretic detection of the result.

Results. No interrelation between the age of patients and polymorphism of any studied gene was recorded at the moment of verification of the diagnosis (р>0.05). Statistically significant relationship was identified between polymorphism of TNF (G308A) gene and the stage of cancer: its homozygous major genotype G/G more commonly occurred in the group of patients with III-IV stage (р=0.047). In the presence of allele of G/G TNF (G308A) gene together with homozygous mutant allele of MMP1 (1607 1G/2G) gene, a direct relationship with increase in the number of patients diagnosed with III-IV stage was noted. This combination of two polymorphisms showed a statistically significant difference in the studied groups (р=0.025). In 8 out of 10 patients with IV stage, the presence of G/G polymorphism in VEGF (C654G) gene was noted. This mutant homozygous variant was much more rare in patents with I (37.5%), II (40%) or III stages (37.5%) (р=0.0147).

Conclusions. The studied genes do not influence the age of manifestation of colorectal cancer and occur at the same frequency in patients of both genders irrespective of the age group. Localization and the extent of differentiation of the tumor do not depend on polymorphism of the studied genes either. The presence of G/A polymorphism of TNF (G308A) gene should be considered a favorable criterion associated with lower aggressiveness of the tumor (р<0.05), whereas identification of the major G/G genotype especially in combination with homozygous mutant allele of MMP1 (1607 1G/2G) gene is an unfavorable factor (р<0.05). The presence of G/G mutant genotype of VEGF (C654G) gene may directly correlate with rapid progression of tumor and with active metastatic spreading (р<0.05).

Keywords

polymorphism of genes / colorectal cancer / invasive growth / metastatic spreading

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RIGHTS & PERMISSIONS

Kulikov E.P., Sudakov A.I., Nikiforov A.A., Mertsalov S.A., Grigorenko V.A.