Five variants were previously reported to confer risk of various malignant or benign tumors (rs78378222 in TP53, rs10069690 in TERT, rs1800057 and rs1801516 in ATM, and rs7907606 at OBFC1) and four signals are located at established risk loci for hormone-related traits (endometriosis and breast cancer) at 1q36.12 (CDC42/WNT4), 2p25.1 (GREB1), 20p12.3 (MCM8), and 6q26.2 (SYNE1/ESR1).
Pooled data analysis suggested that the p53 72Pro variant is a significant endometriosis risk factors in comparison to the 72Arg variant (Pro vs. Arg: OR = 1.298, 95 % CI 1.082-1.558; Pro/Pro vs. Arg/Arg: OR = 1.751, 95 % CI 1.130-2.711; Pro/Arg vs. Arg/Arg: OR = 1.530, 95 % CI 1.174-1.994), which was strengthened in the dominant model (Pro/Pro + Arg/Pro vs. Arg/Arg: OR = 1.570, 95 % CI = 1.181-2.087).
The current meta-analysis suggested that TP53 codon 72 polymorphism was associated with the endometriosis risk, especially in Asians and Latin Americans.
Further, our analysis revealed that the function of AR and p53 in endometriosis is regulated by posttranscriptional changes and not by differential gene expression.
This process was accompanied, however, by a statistically significant modulation of the cell cycle-related proteins p16, p21, p27 and p53 markedly increase following p27(kip1) overexpression in the endometriosis group (p < 0.001) and an increase in apoptotic cells was observed.
This meta-analysis demonstrates that the p53 codon 72 polymorphism may be associated with susceptibility to endometriosis in East Asians, but not in Europeans and Latin Americans.
We found that TP53 72 polymorphism may be associated with susceptibility to endometriosis; the presence of at least 1 polymorphic allele increased the chance of disease development by 2.26-fold.
Inferior 10-year disease-specific survival and progression-free survival were associated with high histologic grade (vs. low and intermediate; P<0.01; 54%±7% vs. 89%±6% and 56%±7% vs. 89%±6%, respectively), presence of TP53 mutation (P<0.04; 54%±12% vs. 64%±10% and 34%±12% vs. 70%±6%, respectively), aberrant p53 expression (P<0.02; 35%±12% vs. 75%±7% and 36%±12% vs. 73%±7%, respectively), and absence of associated endometriosis (P=0.01; 48%±9% vs. 80%±6% and 51%±9% vs. 80%±6%, respectively).
To search for molecular markers of endometriosis the following polymorphisms: p53 codon 72 Pro (apoptosis), TNF alpha-308 (inflammation), VEGF-1164AA (angiogenesis), and SOD2 (oxidative stress) were investigated.
The association of these polymorphisms with p53 gene codon 72 was also evaluated within each group, and a higher frequency of absence of GSTM1 (61%) and GSTT1 (45%) genes in the group of women studied, women with endometriosis and control group was found.
The p53 expression levels were analyzed in the endometrial tissues from endometriosis patients (n=5) and controls (n=4) by Western blot and immunohistochemical analysis.
We evaluated the role of the TP53 16-bp duplication polymorphism by comparing the genotypes of 204 healthy women (controls with surgically excluded endometriosis) to the genotypes of 151 women with endometriosis in the Mexican population.