Objective: The polymorphic variants at codon 72 of the p53 gene, encoding proline or arginine at residue 72, produce marked changes in the p53 structure. From the evidence that the DNA mismatch repair system and p53 interact to maintain genomic integrity, we hypothesized that codon 72 variations may influence the prevalence of microsatellite instability (MSI), a feature of malignancies associated with mismatch repair deficiency in sporadic colorectal cancer.Materials and Methods: We investigated the frequency of MSI in three P53 codon 72 genotypes using genomic DNAs from 144 paraffin blocks of sporadic colorectal adenocarcinomas by testing the BAT-26 poly(A) marker. We used PCR-SSCP analysis to detect tumor sample MSI for the nonisotopic detection of deletions in the BAT-26 poly (A) mononucleotide repeat. Associations between qualitative variables were evaluated using the X2-test. Statistical significance level was set to p≤0.05.Results: MSI analysis revealed that 24.3% of the tumors (n=35) were MSI-positive and 75.7% (n=109) were MSI-negative. The frequency of microsatellite instability in the arginine/arginine, arginine/proline and proline/proline genotypes were 11 (16.9%), 22 (36.1%) and 2 (11.1%) respectively. A significant difference in distribution of MSI was found for the arginine/proline genotype compared with the grouped arginine/arginine and proline/proline genotypes (p=0.05).Conclusion: Our findings suggested that colorectal adenocarcinomas arising in individuals with the p53 codon 72 arginine/proline heterozygosity are more prone to microsatellite instability than those with other p53 genotypes. In our study, MSI was important in the carcinogenesis of sporadic colorectal cancer arising in pro/arg heterozygotes.

Background: Germ-line mutations of BRCA1 and BRCA2 genes are responsible for approximately 25-30% of domi-nantly inherited familial breast cancers; still a big part of genetic component is unknown. The aim of this study was to investigate genetic causes of familial breast cancer in a pedigree with recessive pattern of inheritance.Methods: We applied exome sequencing as a useful approach in heterogeneous diseases gene identification in present study for familial breast cancer. Sanger sequencing was applied for validation and segregation analysis of mutations.Results: Here, we describe a family with three affected sisters of early-onset invasive ductal carcinoma due to hetero-zygous frame shift mutation rs80359352 in BRCA2 gene as the first report in Iranian patients in association with a novel missense SNP of STK11 (p.S422G). These mutations are inherited from their normal father.Conclusion: Despite apparent recessive pattern of inheritance a dominant gene (here BRCA2) can be involved in pathogenesis of hereditary breast cancer which can be explained by incomplete penetrance of BRCA2 mutations.

BACKGROUND: Nuclear factor-kappa B (NF-kB) activation and its inhibition by NF-kB inhibitor (IB) have been functionally linked to germ cell apoptosis, which may affect human infertility. We hypothesized a possible relationship between the NF-kB1-94ins/del ATTG (rs28362491) and NF-kBIA 3’UTR A ®G (rs696) polymorphism, which are common polymorphisms and the susceptibility to oligospermia in the context of the sperm apoptosis.METHODS: In order to evaluate this association, we studied the polymorphisms and sperm apoptosis rates of 114 men with idiopathic oligospermia, as well as 130 normospermic men, using PCR-RFLP and TUNEL staining methods, respectively.RESULTS: Univariate analysis revealed that heterozygous ID genotype at the NF-kB1 -94ins/del ATTG polymorphism is associated with an approximately 2.4-fold reduced risk of oligospermia (P = 0.006, 95% confidence intervall = 1.34 – 4.13). However, the genotype and allele frequencies of NF-kBIA 3’UTR A®G polymorphism, and the genotype frequencies of all possible rs28362491/rs696 genotype combinations did not show any significant differences between oligospermic and normospermic men. Furthermore, neither polymorphism appeared to affect sperm apoptosis, although the sperm apoptosis index was detected to be significantly higher in the oligospermic patients compared with those in the controls (P < 0.05).CONCLUSION: Our findings suggested that the heterozygosity of rs28362491 in the NF-kB1 gene may have a protective effect against oligospermia and could modify the susceptibility of oligospermia in a group with idiopathic male infertility in a Turkish population.