فروزان صفری

Colorectal cancer is the third leading cause of cancer deaths in men and the fourth in women in Iran. Eukaryotic release factor 3 (eRF3) is a GTPase associated with eRF1 in a complex that mediates translation termination in eukaryotes. Apart from its role in translation termination, the eukaryotic translation release factor 3 (eRF3) is involved in several critical cellular processes, such as cell cycle regulation and is essential for the G1 to S phase transition of the cell cycle (GSPT1), cytoskeleton organization, mRNA decay, recycle of ribosomes and apoptosis. Data from two previous studies on polymorphic GGC repeats located in exone 1 of the GSPT1/eRF3 gene suggest that this polymorphic site may play a role in cancer susceptibility.

The GGC expansion was amplified by PCR and alleles in variable size were selected by gelpolyacrylamid and sequenced directly. These sequenced alleles were used as allele specific markers.

In this research, we studies the GGC repeat polymorphism in GSPT1/eRF3 gene among 153 colorectal patients and 280 healthy controls in Isfahan region, Iran. Four different lengths of the GGC repeat in the range of 7,10,11,12 were observed. The most common genotype in controls and patients was homozygous with allele length of 10. Our primary data demonstrate that people carrying allele of 12 GGC specially 11/12 and 12/12 genotypes are at significantly higher risk of developing colorectal cancer.

A direct correlation has been found between the presence of the 12-Gly allele of this gene and development of colorectal cancer (OR = 2.66, P = 0.04). Our results also show a strong association between the allelic lengths of eRF3/GSPT1 polymorphism and family history of colorectal cancer (OR = 10.7, P = 0.0001).

HOXA1 is a transcription factor. In the human mammary gland, the expression of the HOXA1 gene is very low or absent during normal growth and differentiation, but it is expensed at high levels in breast cancer lesions. To date, there has been no study on the relationship between CAC repeat (polyhistidine) in the first exon of HOXA1 gene and the cancer risk. The purpose of this study was to investigate polymorphism of CAC in in the first exon of HOXA1 gene among patients with breast cancer and healthy individuals to clear the relationship of CAC polymorphism in HOXA1 Gene and the risk of breast cancer.

Peripheral blood samples were collected from 193 women with breast cancer and 200 healthy women. After DNA extraction from peripheral blood samples by salting-out method and amplification of desired sequence by polymerase chain reaction (PCR), the number of CAC repeat was determined by polyacrylamide gel electrophoresis and direct sequencing.

Five different length of CAC repeat in the range of 3-7 and 5 allele combinations (genotypes) were observed among patients and controls. The most frequent allele in both patients and controls was the 7-CAC repeat. No significant association was observed between this allele and breast cancer risk. Statistical analyses showed significant association between homozygote 7 and estrogen and progesterone receptors.

Our findings demonstrate that there is no significant association between CAC repeat in exon 1of HOXA1 gene and breast cancer risk. However, there is a significant association between homozygote 7 genotype and estrogen and progesterone receptors.

Genetic alternation in p53 gene is associated with tumorgenesis, especially in breast, colon and lung tumors. Somatic mutation of the p53 gene is the most common genetic alteration seen in human cancers. To our knowledge, before this research, there was no study on the relationship of TAAAA repeat in the first intron of p53 gene and cancer risk. The purpose of this study was to investigate the polymorphism of TAAAA in the first intron of p53 gene among patients with breast cancer and healthy individuals and its relation to risk of breast cancer.

Peripheral blood samples were collected from 200 women with breast cancer and 200 healthy women. After DNA extraction from peripheral blood samples via salting out method and amplification of desired sequence via polymerase chain reaction (PCR), the number of TAAAA repeats was determined using polyacrylamide gel electrophoresis and direct sequencing.

Five different length of TAAAA repeat in the range of 6-10 and 11 allele combinations (genotypes) were observed among patients and controls. The most frequent allele in both patients and controls was the 8-TAAAA repeat. Women who were homozygous for (TAAAA)7 or heterozygous for (TAAAA)6 were at higher risk of developing breast cancer. The allelic length of p53 polymorphisms had no significant effect on the metastasis, the expression of estrogen receptors, progesterone receptors and ErbB2 (HER2) and age of the onset.

Our study shows strong association between the TAAAA repeat polymorphism in p53 gene and risk of breast cancer.