Adenomatous polyposis coli gene large deletions in Iranian patients with familial adenomatous polyposis.

Context: Familial adenomatous polyposis (FAP) is one type of hereditary colon cancer with a large number of precancerous polyps that initiation to growth in childhood and adolescent. Mutation in adenomatous polyposis coli (APC) gene is the cause of FAP. Aims: The aim of the current study was to standardize multiplex ligation probe amplification (MLPA) method in screening of APC large deletions for the first time in Iranian patients with FAP. Subjects and Methods: Deoxyribonucleic acid was extracted from 34 FAP patients by saluting out method. All patients were screened for APC large deletions whit MLPA and for the positive results, respective region was investigated by polymerase chain reaction sequencing. All genetic alterations were doubled checked in two separated rounds of MLPA. Results: The detection rate of large fragment deletions in APC was 5.8% (2/34). Both of the Iranian patients had deletion in the middle and the end of exon 15, however, comparing of clinical features between patient with the large deletion and patients without deletion did not show any significant difference in each variable including, age at diagnosis, signs of disease and poly type. Conclusions: It seems that exon 15 of APC gene is probably the hotspot region in Iranian FAP patients. Association of genotype/phenotype is well known in FAP patients, but in this study statistical analyses did not show a significant difference in each considerable factor between patients with and without large deletions. It seems better to consider MLPA as an initial step to screening APC mutations.

Association between genetic polymorphism of methylenetetrahydrofolate reductase with non familial Colorectal Cancer in Iranian population

Methylenetetrahydrofolate reductase [MTHFR] is a key enzyme regulating folate metabolism, which affects DNA methylation and synthesis. One of the most important polymorphisms identified in the MTHFR gene is C677T. MTHFR activity is lowered in individuals with 677TT genotype. Using pyrosequencing, we analyzed the MTHFR genotypes in 118 colorectal cancer patients and 189 normal matched controls. Whereas the CC, CT and TT genotypes of MTHFR among the colorectal cancer patients were 51.7%, 28.0% and 20.3% respectively, we were able to find 47.1% of 677CC, 27.0% of 677CT and 25.9% of 677TT in normal controls. An inverse association was observed between the risk of colorectal cancer and TT genotype with the odds ratios [OR] of 1, 0.94 and 0.71 for CC, CT, and TT genotypes, respectively. This association was similar in both sexes, but in patients with high levels of folate intake. Our study corroborates previous findings of an inverse association between MTHFR 677TT genotype and colorectal cancer, especially at high levels of folate