P53 gene polymorphisms and breast cancer risk in Arab women

Abstract

The association between polymorphisms in the p53 tumor suppressor gene and breast cancer risk has been studied in many human populations with conflicting conclusions. However, similar studies in Arab women are not available, and the status of these polymorphisms in this ethnic population is not known. We investigated the status of four known p53 gene polymorphisms and their possible role in breast cancer risk in Arab women. Genotyping was performed for 288 breast cancer women and 188 controls to determine Pro47Ser, Arg72Pro, Intron 3 Ins16 bp and intron 6 (G > C) polymorphisms. The p53 variant Pro47Ser was detected only in one Kuwaiti breast cancer patient and was not detected in any of the control subjects. Frequency of Arg/Arg at codon 72 was 26.6% in controls and 28.1% in patients, Arg/Pro frequency was 59.6% in controls and 69.4% in patients, the Pro/Pro genotype was 13.8% in controls and 2.4% in patients. We observed that women with Pro/Pro genotype have decreased risk for developing breast cancer (OR=0.166, 95% CI=0.067-0.411, p<0.001). The intron 3 genotypes were A1/A1 (48.9%), A1/A2 (40.6%) and A2/A2 (10.5%) in controls and A1/A1(42.4%), A1/A2 (52.8%) and A2/A2 (4.8%) in cases. The intron 6 genotypes were 92.4% (GG), 7.6% (GC) and 0% (CC) in controls and 96.5% (GG), 3.5% (GC) and 0% (CC) in cases. No statistically significant differences between patients and controls were observed for intron 3 and intron 6 polymorphisms. Our data show that proline homozygosity at p53 codon 72 is associated with decreased breast cancer risk in Arab women.

The p53 codon 72 polymorphism is associated with risk and early onset of breast cancer among Saudi women

“…In the present study, it was found that 100% of the Saudi women involved in the study carried the wild-type sequence CCG (proline) at codon 47 of the TP53 gene. Similar results were reported in the Kuwaiti population, wherein the the codon 47 variant was detected in only one patient and none of the controls (18). Therefore, the rare sequence TCG (serine) of SNP47, which is thought to reduce the p53 apoptosis ability 5-fold as compared with the wild-type p53 proline 47 (7), is extremely rare or non-existent in the Saudi Arab population.…”

“…Similar results have also been reported regarding cervical cancer (17). Furthermore, Alawadi et al and a recent meta-analysis showed the PP genotype to be associated with decreased breast cancer risk among the Kuwaiti and Indian populations, respectively (14,18). However, Dumont et al found that the proline variant is associated with an increased risk of breast cancer (19).…”

p53 Exon 4 (codon 72) Polymorphism and Exon 7 (codon 249) Mutation in Breast Cancer Patients in Southern Region(Madurai) of Tamil Nadu

“…Polymorphisms in the p53 tumor suppressor gene are potential molecular markers for inherited predisposition for breast cancer (Alawadi et al, 2010). The frequency, timing, and mutation spectrum of the p53 can provide clues to the etiology and pathogenesis of human cancer (Hussain et al, 2001).…”

Studying The Expression of Human P53 Gene in Patients Carrying Breast Cancer.

“…A study in 2011 found that the TP53 proline mutation did have a profound effect on pancreatic cancer risk among males [9]. A study of Arab women found that proline homozygosity at TP53 codon (72) is associated with a decreased risk for the breast cancer [10] [11] [12]. One study suggested that TP53 codon 72 polymorphisms, p53 mutation still the most common genetic change named in human neoplasia.…”

“…Molecular pathological analysis of the structure and expression of constituents of the p53 pathway is likely to have value in diagnosis, in prognostic assessment and ultimately in treatment of breast cancer [13]. Another study found the suppressor protein 53 homozygous (Pro/Pro) genotype was associated with a significantly increased risk for renal cell carcinoma [10] [14] [15] [16]. According to recent researches, P53 mutations are highly correlated in human breast cancer.…”