The results are interpreted as suggesting that the tumorigenic potential of radiochemotherapy is mediated via induction of genetic instability in exposed cells. Long after the therapy, the instability may become an initiating event in the development of new malignancies in affected tissues, whereas the instability induced in haemopoietic stem cells may reveal itself in peripheral lymphocytes derived from formerly exposed precursors.
Genes encoding proteins with antioxidant properties may influence susceptibility to endometrial hyperplasia (EH) and endometrial carcinoma (ECa). Patients with EH (n = 89), EH concurrent with ECa (n = 76), ECa (n = 186), and healthy controls (n = 1110) were genotyped for five polymorphic variants in the genes involved in metabolism of lipoproteins (APOE Cys112Arg and Arg158Cys), iron (HFE Cys282Tyr and His63Asp), and catecholamines (COMT Val158Met). Patients and controls were matched by ethnicity (all Caucasians), age, body mass index (BMI), and incidence of hypertension and diabetes. The frequency of the APOE E 2 allele (158Cys) was higher in patients with EH + ECa than in controls (P = 0.0012, P
Bonferroni = 0.018, OR = 2.58, 95% CI 1.49–4.45). The APOE E 4 allele (112Arg) was more frequently found in patients with EH than in controls and HFE minor allele G (63Asp) had a protective effect in the ECa group, though these results appeared to be nonsignificant after correction for multiple comparisons. The results of the study indicate that E 2 allele might be associated with concurrent occurrence of EH and ECa.
The distribution of APOE 4 allele (rs 429358, C) was analyzed in healthy women (N=454) and patients with ovarian serous adenocarcinoma (N=114) in order to identify genetic predisposition to the disease. We determined the prognostic indicators of the E4 allele as a marker: odds ratio (OR) and AUC (Area Under Curve) - an area under the ROC curve. It was shown that APOE 4 allele was significantly associated with ovarian serous adenocarcinoma (p = 0,003; 0R=1,94; AUC=0,55). The Е4 genotypes frequency was significantly increased among patients (p = 0.02; 0R=1,8). Separate analysis of the two age subgroups (over 46 years and younger) found that the chance of developing ovarian serous adenocarcinoma was significantly increased for older women (p = 0,006; OR = 2,24, AUC = 0,76). Possible associations of APOE 4 with the ovarian serous adenocarcinoma in women of reproductive age deserve further studying.
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