Validation of PCR-RFLP techniques for the evaluation of codon 72 of p53 and CYP1A1 gene's polymorphisms in relation with ovarian cancer in a Romanian population.

Epidemiological studies suggest that the onset and progression of ovarian cancer are associated with the presence of estrogens. CYP1A1 gene has two polymorphisms, which may affect the estrogens' metabolites and contribute to increased susceptibility to neoplastic transformation of ovarian cells. P53 is a tumor suppressor gene, which acts to preserve stability of human genome. Codon 72 polymorphism of p53 gene was correlated with susceptibility for ovarian cancer. The aim of our study was to validate the use of PCR-RFLP techniques for the evaluation of p53 codon 72 and CYP1A1 gene polymorphisms in relation with ovarian cancer in a Romanian population and to evaluate gene-environment interaction in this context. The case-control study included 42 subjects. The assessment of risk and protective factors was performed using a questionnaire. Polymorphisms of CYP1A1 and p53 genes were assessed using the validated PCR-RFLP techniques. The statistical analysis was performed using Epi Info 3.5.1 software. Frequency of Arg/Arg genotype of p53 gene was higher among cases (43%) compared with controls (33.3%), but the difference was not statistically significant (p=0.75). The presence of Ile/Val polymorphism of CYP1A1 gene was identified in 9.5% of the cases and the MspI polymorphism of CYP1A1 gene was not identified in our subjects. Validation of techniques consisted in the optimization of RFLP methods for p53 and CYP1A1 genes polymorphism analyzing that allowed highlighting the existence of codon 72 polymorphism of p53 gene and Ile/Val polymorphism of CYP1A1 gene in the population from this region.

Research on aromatase gene (CYP19A1) polymorphisms as a predictor of endocrine therapy effectiveness in breast cancer.

UNLABELLED: Single nucleotide polymorphisms (SNPs) of the CYP19A1 gene have shown the ability to modify its activity, but no association has been established with aromatase inhibitor (AI) efficiency in hormone receptor positive breast cancer (BC). MATERIAL AND METHODS: The study included blood samples from 53 patients (p) with BC and 1 control (male DNA); 22p. (investigational group) were administered an Al and followed up. RESULTS: Homozygous (hh) -CC and TT -, and heterozygous (hz) - TC - genotypes of the rs10046 SNP were balanced. Response to treatment or progression were not affected (p=0.630) in patients with T allele 1; local relapse occurred significantly more rarely and overall survival (OS) was superior (p=0.046). For rs4646, genotypes were mainly hhGG (57%), with no implication to study parameters (p>0.05). For rs727479 SNP, major genotypes were hhTT (40%) and hzTG (45%). Therapeutic response was better in patients with T allele 2 (p=0.040), T allele 1 was associated with reduced local recurrence (p=0.047) and TT genotype with better OS (p = 0.008). In rs700518 SNP, genotype was mostly hzGA (49%). Local recurrence rates were reduced in the presence of G allele 1 (p=0.047) and GG homozygosity. CONCLUSIONS: At this stage, the study was purely exploratory and hypothesis generating. Genotyping of at least three of the four CYP19A1 SNPs evaluated (except rs4646) may have an impact in clinical practice, providing better criteria for patient selection, prognosis and therapeutic decision in BC.

The assessment of relations between main histologic type of ovarian cancer and some risk and prognostic factors.

UNLABELLED: The authors have highlighted some aspects regarding the domestic risk and prognostic factors for different types of ovarian cancer. MATERIAL AND METHOD: The study has included 249 women diagnosed with ovarian cancer. RESULTS: The assessment of age group distribution of patients with serous carcinoma (150 cases) underlying that the age group of 60-69 years was more frequent compared with the other age groups (OR = 0.20; IC 95% = 0.12-0.33; p < 0.01 x 10(-5)) and the mean of age was 61 years, 8 months, 19 days (DS = 11 years, 11 months, 22 days). The most frequent risk factor for serous type was the ovulation lifetime over 30 years (78.66%); followed by early menarche (under 12 years) (13.33%); smoking (12%); late menopause (over 52 years) (10%) and hormone replacement therapy (HRT) (2.67%), compared with mucinous carcinoma for which the most frequent was the ovulation lifetime over 30 years (65.21%); followed by early menarche (under 12 years) (34.78%); late menopause (over 52 years) (26.08%) and smoking (17.39%). CONCLUSIONS: The ovulation lifetime over 30 years was identified as the main risk factor for both histological types, but it was significant more frequent among women with serous type. Smoking was more frequent among those who had mucinous carcinoma compared with serous type. No significant differences were identified among women with both histological types regarding the age at first menstrual bleeding and parity.

Using MLPA for large genomic rearrangements detection in breast cancer predisposition genes.

UNLABELLED: Breast and ovarian cancer are common pathologies in women, with increasing incidences worldwide. In hereditary breast and ovarian cancer (HBOC) families, a large percentage of cases are attributable to hereditary factors compatibles with dominant autosomal transmission of a major tumour suppressor gene with incomplete penetrance. Screening for BRCA1 mutations is now standard practice for HBOC cases in western world, and permits medical follow-up and genetic counselling. Over 300 BRCA1 germinal mutations are stored in the Breast Cancer Information Core (BIC) mutation database. MATERIAL AND METHODS: Estimates in different countries range from 5 to 15% the BRCA1 related cases of hereditary breast cancer due to copy number changes of one or more exons of this gene. Exon deletions and amplifications will usually not be detected by sequence analysis of the complete BRCA1 gene, therefore MLPA screening is needed. RESULTS: Here we describe Multiplex Ligation-dependent Probe Amplification technique (MLPA) implementation for BRCA1 large genomic rearrangements. CONCLUSIONS: We did not detect any BRCA1 mutation by analysis of 15 HBOC recruited patients.

[Specifics of individual risks in a group of women with genital neoplasms]. / Particularitati privind riscurile individuale la un lot de femei cu neoplazii genitale.

UNLABELLED: Genital cancers represent an important issue regarding women health, as they produce a large number of cases, invalidities and deaths. AIM: The evaluation of individual risks for a group of women with genital neoplasia. MATERIAL AND METHODS: We conducted a pilot case-control study to validate the questionnaire for the evaluation of risk factors in genital cancers, in a number of 40 female subjects (20 cases and 20 controls). We have realized the data processing using the SPSS 16 and EpiInfo 3.5.1. soft wares. RESULTS: For questionnaire validation we have evaluated the reproducibility, the validity, the acceptability and the practicability of the questionnaire. In order to establish the test reproducibility, we have calculated k factors for inter-investigator (k = 0.34) and intra-investigator (k = 0.72) variation. To evaluate the questionnaire validity we calculated the sensitivity (cases = 94%; controls = 97%), specificity (cases = 67%, controls = 75%), positive predictive value (cases = 94%; controls = 94%), negative predictive value (cases = 67%; controls = 86%). The risk factors most frequently identified were genital infectious in clinical records (75% comparing to 52.5% - p = 0.036), and also the presence of other pathological records in genital area (65% comparing to 22.5% - p = 0.0001). CONCLUSIONS: For an accurate identification of individual risk at women with genital cancers subsequently studies on greater number of subjects is necessary.