Significance of gene polymorphysm in development of colorectal cancer

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 1G2G), 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 (р0.05). 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 (р0.05), 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 (р0.05). The presence of G/G mutant genotype of VEGF (C654G) gene may directly correlate with rapid progression of tumor and with active metastatic spreading (р0.05).

Association of XRCC1, HMMR genes with breast cancer in the Kyrgyz ethnic group

An association of genes XRCC1 and HMMR with breast cancer (BC) has never been tested in the Kyrgyz ethnic group. This was a case-control study of 201 women of the Kyrgyz ethnic group with a morphologically verified breast cancer (N=99) and 102 controls age-matched with BC cases. The mean age of the patients was 53 years (24–74, SE mean = 0.967, STD=9.81). The extraction of DNA was carried out from venous blood. The genotyping was conducted by using the method of polymerase chain reaction and restriction fragment length polymorphism. When comparing the results of genotyping, the histological structure of the tumor and the «menopause» factor, Fisher»s exact test was used. Calculation of the odds ratio was carried out by cross tabulation method. A statistically significant link between the XRCC1 Arg194Trp polymorphism and the menopausal status was observed (p=0,018). The Arg / Arg genotype of XRCC1 Arg194Trp polymorphism occurred in 52 % of cases in women at menopausal age, whereas in women before the onset of menopause, the genotype Arg / Arg occurred in 78.8 % of BC cases (p=0.009). The CT genotype of HMMR V353A polymorphism was identified as “protective” factor – OR=0.481, 95 % CI [0.27‑0.85]. There was no statistically significant association between the results of genotyping and histological structure of the tumor, as well as the age of verification of the diagnosis of BC.