Twenty-one X-chromosomal short tandem repeat loci, including the six clusters of linked markers DXS10148-DXS10135-DXS8378 (Xp22), DXS7132-DXS10074-DXS10079 (Xq12), DXS6801-DXS6809-DXS6789 (Xq21), DXS7424-DXS101 (Xq22), DXS10103-HPRTB-DXS10101 (Xq26), DXS8377-DXS10146-DXS10134-DXS7423-DXS10011 (Xq28), and the loci DXS6800 and GATA172D05 were typed in a northwestern Algerian population sample (n = 210; 104 men and 106 women). Allele and haplotype frequencies were calculated. No evidence of linkage disequilibrium was observed between pairs of loci within clusters of linked markers. At locus DXS10148, sequence analysis of a subset of alleles displaying unusual amplicon length (>/= 36 repeat units) and anomalous electrophoretic mobility showed that this marker has a complex molecular structure with different repeat variants within alleles of identical amplicon size.

No abstract

We have demonstrated, for the first time in the West Algerian population, that these polymorphisms were not predictive for clinical response and/or ADRs to MTX therapeutic outcome.

The tumor suppressor gene TP53 and its regulator MDM2 are both key players involved in multiple pathways including apoptosis, cellular transcriptional control and cell cycle regulation. Common germline polymorphisms in these genes may affect colorectal cancer (CRC) susceptibility. An arginine-to-proline substitution at codon 72 in the TP53 gene is reported to decrease apoptotic potential, while a thymine-to-guanine polymorphism at nucleotide 309 (named SNP309) of murine double minute 2 MDM2 gene increases its transcription. These two polymorphisms therefore may be of importance in colorectal carcinogenesis. The relation of these polymorphisms to colorectal cancer in the Algerian population was addressed in this study. DNA samples from 121 controls and 116 cases were genotyped for these two polymorphisms by PCR/RFLP then confirmed by sequencing. Unexpectedly no significant association was found between this potential marker TP53 Arg72Pro and CRC (p > 0.05). However, our findings reveal that individuals with the MDM2 SNP309 GG genotype have a low risk of CRC as compared to the TT genotype (OR = 0.49; 95 % CI: 0.24-0.98, p = 0.04), with more significance for females (OR = 0.16; 95 % CI: 0.06-0.41, p < 0.05). Moreover, no significant association was observed between the combined TP53 and MDM2 genotypes and CRC. Contrary to initial expectations that the GG genotype with high MDM2 levels would increase cancer risk, our results demonstrate that the MDM2 SNP309 GG genotype is associated with decreased risk of colorectal cancer. This is suggesting that other mechanisms independent of increased MDM2 levels can influence cancer susceptibility.

Colorectal cancer (CRC) is a complex and multifactorial disease, in which genetic and environmental factors both seem to play a part. Many epidemiological studies have explored the association between genetic polymorphisms of X-ray repair cross-complementing group 3 (XRCC3) (Thr241Met) and Xeroderma pigmentosum group D (XPD) lysine to glutamine at codon 751 (Lys751Gln) and risk of CRC in various populations; however, the results are controversial. We conducted this case-control study in a West Algerian population to assess the potential role of this genetic polymorphism on the risk of CRC in this population. Genomic DNA was extracted from blood samples collected from 129 sporadic CRC patients and 148 normal controls. The polymorphisms were determined by pyrosequencing technique. The distribution of XRCC3 Thr241Met and XPD Lys751Gln genotypes among controls did not differ significantly from those predicted by the Hardy-Weinberg distribution (p > 0.05). There were no significant differences in the genotypes distribution and allele frequencies between CRC patients and controls. A significant association was found between the combined heterozygous of XRCC3 and homozygous variant of XPD gene and CRC. This is the first study on DNA repair genetic polymorphisms in West Algerian population, and it suggests that the XRCC3 Thr241Met and XPD Lys751Gln polymorphisms may not be associated with the CRC risk in this population.