P-194 - Association of the -4791 A/T and the -4601A/G polymorphisms of the distal promoter of RAD51 gene with a risk of colorectal cancer

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Colon Cancer
Translational Research
Presenter I. Majsterek
Citation Annals of Oncology (2015) 26 (suppl_4): 1-100. 10.1093/annonc/mdv233
Authors I. Majsterek, B. Mucha, K. Przybylowska-Sygut, A. Dziki, L. Dziki
  • Medical University of Lodz, Lodz/PL



Colorectal cancer (CRC) is one of the most common cancers in developed countries. Annually, over one million of new cases in the world are recorded. Majority of CRCs occur sporadically with dominant phenotype of chromosomal instability (CIN). DNA damage may result in double-stranded breaks, which create favorable conditions for chromosomal aberration to arise. Homologous recombination repair (HRR) is the leading process engaged in maintaining of the genome integrity. RAD51 protein is recognized as crucial in HRR. Single nucleotide polymorphisms (SNPs) are the primary source of genetic variation and their presence in the RAD51 promoter region can effect on its expression and consequently the ability to modulate the HRR.


The aim of this study was to analyze the distribution of genotypes and allele frequencies of the -4791 A/T (rs5030789) and the -4601A/G RAD51 (rs5030789) polymorphisms of the promotor region of RAD51 gene, followed by an assessment of their relationship with the risk of CRC. The genotypes were identified by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method with NlaIII (rs5030789) and HindIII (rs2619679) enzymes, respectively. The Pearson Chi2-test was used for Hardy–Weinberg Equilibrium (HWE) analysis and the association between a genotypes/alleles occurrence and an outcome (CRC) was estimated through calculating odds ratios with 95% confidence intervals.


The study included 115 patients with confirmed CRC. Control group is consisted of 118 cancer-free individuals with a negative family history. Hardy-Weinberg (HW) chi-square analysis have shown that distribution and frequency of genotypes of control group for −4601A/G (rs5030789) polymorphism (X2 = 0.26; p= 0.61) is consistent with HW equilibrium in contrary to CRC patients group (X2 = 8.87; p= 0.0029). In the second SNP −4719A/T (rs5030789), distribution of genotypes in both control group (X2 = 2.6; p= 0.11) and patients (X2 = 1.06; p= 0.3) corresponded to HW equilibrium. The frequencies of genotypes in -4601G/A polymorphism of RAD51 was 34% for GG, 61% for G/A and 9% for AA, allele G 61% and allele A 34%. The odd ratio value indicates an increased risk of CRC for heterozygous model A / G (OR = 1,854 95% CI= 1,063-2,256). For the second investigated polymorphism the fallowing frequencies was determined: 22% for A/A, 55% for A/T, 23% for TT and 49% for allele A, 51% for allele T. Statistical analysis have shown lack of association with CRC.


This is one of the first reports focused on −4719A/T (rs5030789) and −4601A/G genetic variation. This study reveals statistically significant association of CRC risk with polymorphisms of the promotor region of RAD51 gene. Outcomes of our study indicate an increased risk of CRC appearance in patients with genotype A/G at the position -4601. Therefore, we suggest that the -4601 A/G polymorphism of RAD51 gene may be used as a predictive factor in pathogenesis of colorectal cancer but future studies are needed to elucidate its role of in carcinogenesis.

This work was supported by grant no. N N403 250 340 from the Polish Ministry of Science and Higher Education (MNiSW).