Development of a high-resolution melting method for screening R188h polymorphism in XRCC2 gene

The High Resolution Melting [HRM] method is a new scanning method for detecting unknown changes in DNA and its advantages have persuaded researchers to recruit it as a screening method. Here, we developed a HRM method to screen R188H SNP [rs3218536] of XRCC2 and compared the results with a well known PCR-RFLP technique. Genomic DNA samples from 350 healthy individuals were obtained. PCR-HRM analysis and PCR-RFLP method were performed simultaneously. Three different melting profiles corresponding to three different genotypes recognized by HRM analysis. The results of PCR-RFLP showed no discrepancy. We concluded that the HRM technique can be used as a screening method for rapid discrimination of R188H genotypes in XRCC2 gene.

Analysis of relation between C677T genotype in MTHFR gene and prostatic cancer in Iranian males

Methylenetetrahydrofolate reductase [MTHFR] enzyme is one of the most important enzymes with a pivotal role in the folate metabolism and DNA synthesis pathways. Single nucleotide polymorphism [SNPs] in the coding gene has been related to many medical diseases as well as diverse malignancies including the prostate cancer which is the leading cause of the cancer deaths in men and one of the major public health problems. The goal of this study is to determine the relationship between the MTHFR C677T SNP and the prostate adenocarcinoma in Iranian males attending to the Labbafi-nezhad hospital in Tehran. In this Case-control unmatched study, 67 and 75 paraffinized tissue samples were taken out of the specimens diagnosed previously as the prostatic adenocarcinoma and nodular prostatic hyperplasia for the case and control groups respectively. MTHFR C677T genotyping was done by the use of multiplex ARMS-PCR and frequencies of the alleles were compared between the case and control groups as well as calculating the deviation from Hardy-Weinberg equilibrium and Odds Ratio for the "T" allele regarding the prostatic carcinoma. The observed rates in the control group were not too different from that of expected from Hardy- Weinberg equilibrium [P=0.407]. Frequencies of the possible genotypes were as follows: CC, 43.28% vs. 42.67%; CT, 49.25% vs. 52% and CT, 7.46% vs. 5.33% in the case and control groups respectively [P=0.85]. 1.37 times increased risk was found for the homozygote carriers of C677T variant [OR: 1.37, 95% CI: 0.33- 5.6; P=0.653] which is however statistically not significant. No association has been evident between the MTHFR 677C>T polymorphism and the risk of prostatic carcinoma in this study confirming the findings of some of the previous attempts; however, [OR: 1.37, 95% CI: 0.33-5.6] implies a slight effect of the homozygote on the carcinogenesis. Thus larger studies especially with a greater number of the smaples are recommended

role of Ile3434Thr XRCC7 gene polymorphism in differentiated thyroid cancer risk in an Iranian population

The aim of this study was to understand any association between differentiated thyroid carcinoma [DTC] and Ile3434Thr XRCC7 gene polymorphism [GenBank accession number: rs7830743]. DTC is the most prevalent thyroid neoplasm, which includes papillary and follicular cell carcinoma. XRCC7 gene encodes a protein that functions in non-homologous end joining DNA repair pathway. Non-synonymous polymorphisms in this gene may alter DNA repair capacity of the cell and change the risk of developing cancers. DTC patients [n = 173] and cancer free individuals [n = 204] were enrolled in a case-control study. The Ile3434Thr polymorphic alleles were discriminated by using amplification refractory mutation system-PCR method. The frequencies of this single nucleotide polymorphism in case and control groups were compared. Also, risk ratio for developing DTC in dichotomized genotypes was estimated by multivariate logistic regression analysis. Dichotomized genotypes into those with and without the 3434Thr allele showed that this allele was associated with DTC [OR [odd ratio]: 1.89, 95% confidence interval [CI] = 1.29-2.79, P<0.001]. Also, TC genotype was significantly associated with increased risk of DTC [OR: 2.42, 95% CI = 1.55-3.81, P = 0.0001] in individuals carrying this genotype. Allele 3434Thr in XRCC7 gene might be associated with differentiated thyroid cancer risk. Further studies with larger samples are needed to verify these initial findings

Association of Arg194Trp, Arg280His and Arg399Gln polymorphisms in x-ray repair cross-complementing group 1 gene and risk of differentiated thyroid carcinoma in Iran

X-ray repair cross-complementing group 1 [XRCC1] gene is a DNA repair gene and its non-synonymous single nucleotide polymorphisms [SNP] may influence DNA repair capacity which has been considered as a modifying risk factor for cancer development. A case-control study was conducted to investigate impact of three frequently studied polymorphisms [Arg194Trp, Arg280His and Arg399Gln] on developing differentiated thyroid carcinoma [DTC]. Increased risks for DTC were shown in homozygous [odds ratio [OR]: 3.66, 95% confidence interval [CI]: 0.38-35.60] and in dominant trait [OR: 1.22, 95% CI: 1.64-2.32] of Arg194Trp genotype. Also, for Arg280His genotype, an increased risk for DTC was shown in dominant trait [OR: 1.42, 95% confidence interval [CI]: 0.76-2.68], while a mildly reduction of risk for DTC [OR: 0.77, 95% [CI]: 0.50-1.17] was estimated in dominant Gln genotype of Arg399Gln. Considering combinatory effects of Arg194Trp and Arg280His genotypes on DTC, the calculated OR and 95% CI for being heterozygous for one of Arg194Trp or Arg280His genotypes were 1.57 and 0.90-2.74, respectively. Genotyping of codons 194, 280 and 399 in XRCC1 gene may use in risk assessment of DTC