Importance of ATM gene as a susceptible trait: predisposition role of D1853N polymorphism in breast cancer

Abstract

The involvement of ATM gene and specifically, the important role of D1853N polymorphism, as a three-hit hypothesis has been previously reported in an Iranian proband affected with brain tumor and this polymorphism could be screened in her relatives as well. The aim of present study was to investigate the involvement of D1853N polymorphism as a predisposition factor in 129 Iranian patients affected with primary breast cancer and 248 sex- and age-matched healthy controls. Mutant allele-specific PCR amplification (MASA) assay was performed to analyze the D1853N polymorphism in the ATM gene. The frequency of D1853N polymorphism in cases, internal and external controls was 31.0% (40/129), 26.9% (28/104) and 12.5% (18/144), respectively. The frequency of D1853N in total control groups, including normal external control and pedigree internal control, was 18.6% (46/248). The odds ratio was calculated with the logistic regression test, with an estimated relative risk of 2.579 (P=0.005). The significant difference was observed between the patient-carriers of this alteration and external controls (P=0.001). The number of controls harboring D1853N polymorphism was higher in internal control compared to external controls, and the difference was statistically significant (P=0.004). The significant difference was observed between the patient-carriers and external controls and could be considered as a predisposing and diagnostic marker in the population and specifically in the cancer-prone pedigrees.

ATM polymorphisms IVS24-9delT, IVS38-8T>C, and 5557G>A in Mexican women with familial and/or early-onset breast cancer

“…Similar results were found by Mehdipour and colleagues 14 in Iranian population, in which the authors found a heterozygote frequency of 31% in cases vs. 18.6% in controls. These results differ significantly from those obtained in this study, probably because they are populations with different genetic background.…”

“…The polymorphism 5557G>A (D1853N), located in exon 39 of the ATM gene, has been studied by Mehdipour and colleagues, 14 who proposed it as a predisposing factor for developing BC, especially in familial cases. The study was conducted in an Iranian population of women with BC and in a healthy control group divided into two subgroups, one randomly selected and the other with a family history, reporting a carrier frequency of 31% in the disease group and 18.6% in controls.…”

Association between polymorphisms of the ataxia telangiectasia mutated gene and breast cancer risk: evidence from the current studies

“…Of these studies, the sample sizes ranged from 184 [13] to 2,884 [11] individuals. One study deviated from the HWE at a significance level of P = 0.01 in controls [11] and another two studies by Mehdipour et al [18] and Koren et al [13] had no available data for HWE. The genotypes and separate P values for ATM 5557G[A, IVS38-8T[C, IVS1?19A[T, and IVS34?60G[A polymorphisms included in the meta-analysis are shown in Table 2.…”

“…Following the above inclusion and exclusion criteria, nine publications were included in this meta-analysis [4,[11][12][13][14][15][16][17][18]. Some case-control studies presented the ORs separately for more than one kind of ATM polymorphism [4,11,15,16].…”

Are polymorphisms of the ataxia telangiectasia mutated gene associated with breast cancer risk?

“…However, as the study by Tapia et al [3] was not in Hardy-Weinberg equilibrium (HWE) in controls, it should be excluded in the final meta-analysis. In addition, the meta-analysis by Gao L et al [2] omitted one eligible study [8] and included one ineligible study [3]. Therefore, we re-assessed the association between ATM 5557G[A polymorphism and breast cancer (Fig.…”