Association of TP53 PIN3 polymorphism with breast cancer in Moroccan population

Abstract

TP53 is a tumor suppressor gene involved in cell cycle progression control, DNA damage repair, genomic stability, and apoptosis. Some polymorphisms in this gene have been associated with the development of a number of cancers including breast carcinoma. PIN3 Ins16bp polymorphism has been widely studied in different populations for an association with breast cancer risk. In most case-control studies, a duplicated allele has been more frequent in cases rather than controls but there are also inconsistent results. The present study aimed to assess the association of PIN3 Ins16bp polymorphism of p53 with breast cancer risk in Moroccan population. This case-control study was performed on 105 female patients with confirmed breast cancer and 114 healthy controls. The genotype frequency was 69.5 % (A1A1), 26.7 % (A1A2), and 3.8 % (A2A2) in patients and 68.4 % (A1A1), 24.6 % (A1A2), and 7 % (A2A2) in controls. No statistically significant association was observed between PIN3 Ins16bp polymorphism and breast cancer risk with odds ratio of 1.07 (confidence interval (CI) = 0.58-1.97, p = 0.83) for the heterozygous A1A2 and 0.53 (CI = 0.15-1.85, p = 0.32) for mutated homozygous A2A2.According to our preliminary genetic analysis, PIN3 Ins16pb polymorphism could not be assessed as a marker of risk factor for predisposition to breast cancer in Moroccan population. However, a high frequency of A2 allele (19.3 %) in our population suggested that PIN3 Ins16pb polymorphism may be a valuable marker for study in other cancers with larger groups.

Association of PIN3 16-bp Duplication Polymorphism of TP53 with Breast Cancer Risk in Mali and A Meta-analysis.

“…Similar results have been found in the Iranian population by Faghani et al who reported a correlation between invasive ductal breast cancer and the PIN3 duplication polymorphism at 16 bp [41]. Contrary to our observations, studies carried out in the Moroccan, Croatian and Czech populations have not found any link between histological types and mutations in this gene [20,27,35]. These contradictory results may be explained by the ethnic and geographic origin.…”

“…PCR ampli cation conditions were previously described by Maarouf and al. [20]. The PCR products after electrophoresis on a 4.5% agarose gel showed a fragment of 119 bp for the A1 allele (wild type or no duplication) and a fragment of 135 bp for the A2 allele (Insert or 16-bp duplication).…”

“…This disturbance is involved in the etiopathology of many cancers, including breast cancer [15,16]. Several studies around the world have found an association between the polymorphisms of this gene and the development of breast cancer [17,18], while others have found no effect [19][20][21]. It has been reported in developed countries that individuals harboring the A2A2 genotype or 16-bp duplication in intron 3 of TP53 are at increased risk of breast cancer [22,23].…”

“…It has been reported in developed countries that individuals harboring the A2A2 genotype or 16-bp duplication in intron 3 of TP53 are at increased risk of breast cancer [22,23]. However, very few studies have been performed in Africa populations [20], especially in Mali. The literature review revealed that the association between the PIN3 16 bp duplication polymorphism and the risk of breast cancer has not been evaluated in our population.…”

The bone marrow metastasis niche in retinoblastoma

“…It responds to different cellular stress signals by regulating gene expression, which may lead to the induction of cell cycle arrest, apoptosis, senescence, DNA repair and/or metabolic modifications within the cell [18]. P53 inhibitor proteins include MDM2 and MDMX, and their increased turnover is a characteristic of many tumors [19].…”