Wyniki przesiewowych badań prenatalnych w materiale 2285 ciąż z rejonu Pomorza Zachodniego diagnozowanych w latach 2005-2006

Summary In the following paper we have presented the results of non-invasive and invasive prenatal diagnostic tests performed on 2285 pregnant women from the Western-Pomeranian Region between 2005 and 2006. Material and methods: Retrospective analysis of screening tests on 2285 pregnant women. Medical history, including age, weight, familial data pedigrees up to third degree relatives, accompanying diseases, gestational complications in the family, type, dosage and period of any drugs intake, was obtained. Sonographic screening and evaluation of maternal serum PAPP-A and betaHCG levels. Results: Screening tests identified 4.5% high-risk pregnancies in this group. 69% of the patients consented to invasive diagnosis. As a result, genetic anomalies were detected in 43.7% of cases. Significant differences in betaHCG levels correlated with oral gestagens intake and place of residence (coastal areas). Conclusion: Broad use of certified non-invasive methods of prenatal screening allow substansial reduction of invasive procedures with high levels of positive prediction. Medical drugs intake as well as place of inhabitation may influence on free betaHCG levels.Streszczenie Cel pracy: Celem pracy było przeanalizowanie wyników nieinwazyjnych i inwazyjnych badań prenatalnych przeprowadzonych w regionie zachodniopomorskim w latach 2005-2006. Materiał i metody: Analiza retrospektywna 2285 ciąż. Wywiad z uwzględnieniem 3 pokoleniowego rodowodu, badania ultrasonograficzne I trymestru wraz z testem podwójnym. Amniopunkcje ze standardową oceną kariotypu. Wyniki: Drogą badań przesiewowych wyłoniono 4,5% ciąż podwyższonego ryzyka, z których 69% poddało się amniopunkcji. Pozwoliło to na potwierdzenie w wysokim odsetku (43,7%) nieprawidłowości genetycznych. W badanej grupie ciężarnych zaobserwowano istotne zmiany w parametrach biochemicznych betaHCG zależne od przyjmowanych leków (gestageny) oraz od miejsca zamieszkania (okolice nadmorskie). Wnioski: Powszechne zastosowanie certyfikowanych nieiwazyjnych badań prenatalnych pozwala na ograniczenie liczby przeprowadzanych amniopunkcji przy utrzymaniu wysokiego wskaźnika predykcji. Doustne przyjmowanie niektórych leków oraz miejsce zamieszkania pacjentki może wpływać na poziomy wolnej podjednostki betaHCG

The 3020insC Allele of NOD2 Predisposes to Cancers of Multiple Organs

The NOD2 gene has been associated with susceptibility to Crohn's disease and individuals with Crohn's disease are at increased risk for cancer at a number of organ sites. We studied the association between the 3020insC allele of the NOD2 gene and cancer among 2604 cancer patients and 1910 controls from Poland. Patients were diagnosed with one of twelve types of cancer in the Szczecin region between 1994 and 2004. Significant associations were found for colon cancer (OR = 1.8; 95% CI 1.2 to 2.6), for lung cancer (OR = 1.7; 95% CI = 1.1 to 2.5) and for ovarian cancer (OR = 1.6; 95% CI 1.1 to 2.3). In addition, a significant association was found for early-onset laryngeal cancer (OR = 2.9; 95% CI 1.4 to 6.2) and for breast cancer in the presence of DCIS (OR = 2.1 95% CI = 1.2 to 3.6). The NOD2 3020insC allele is relatively common (in Poland 7.3% of individuals) and may be responsible for an important fraction of cancer cases. We estimate that the lifetime cancer risk among carriers of this allele is 30% higher than that of individuals with two wild-type alleles

Mutacja 3020insC w genie NOD2 u chorych z rakiem jajnika

Summary Objective: There is an increasing evidence that genetic factors play a role in the etiology of malignant tumors. Mutations of BRCA1 and BRCA2 genes are responsible for an increased risk of ovarian cancer. The role of mutations in NOD2 gene in this type of neoplasm is still under investigation. The aim: The aim of this study was to determine: 1. incidence of NOD 2 3020insC constitutional mutation in a group of consecutive women with ovarian cancer, 2. risk of developing ovarian cancer in patients with NOD2 gene mutation, 3. clinical and pathological features of ovarian cancer in NOD2 gene mutation carriers. Patients and Methods: Clinical and pathological data were collected from 257 non-selected patients with primary epithelial ovarian cancer. The researches identified NOD2 3020insC gene mutation. On the basis of patient source documentation we obtained the data concerning the age of patients at diagnosis, histopathological recognition, FIGO stage and morphological grade G. Results: 19 out of 257 women were identified with germ-line 3020insC mutation of NOD2 gene (7.39%). An increased risk of ovarian cancer in NOD2 mutation carriers was not revealed (OR=1.01; p=0.928; 95%CI=0.61-1.66). The mean age at diagnosis of patients with NOD2 mutation was 54.8 (SD=9.9), while for non-carriers it was 53.2 (SD=10.2). The difference between these frequencies was statistically irrelevant (p=0.550). Clinical and pathological profile of ovarian cancer was made. We assessed the following features: age at disease onset, histopathology, FIGO stage and morphological grade G. For NOD2 mutation carriers no statistically significant features of ovarian cancer were revealed. Conclusion: 1. Despite high frequency of constitutional mutations occurrence in NOD2 gene in women with ovarian cancer, genetic testing seem not to be justified in all women diagnosed with this disease.Streszczenie Wstęp: Obserwuje się coraz więcej dowodów na rolę czynników genetycznych w rozwoju nowotworów. Wiadomo, że mutacje w genie BRCA1 i BRCA2 odpowiadają za podwyższone ryzyko rozwoju raka jajnika. Znaczenie innych zaburzeń genetycznych takich jak mutacje w genie NOD2 jest ciągle jeszcze badane. Cel pracy: Celem badania było określenie: 1. częstości występowania mutacji konstytucyjnej NOD2 3020insC w grupie nieselekcjonowanych kobiet z rakiem jajnika, 2. ryzyka rozwoju raka jajnika u pacjentek z mutacja genu NOD2, 3. cech patologiczno-klinicznych raka jajnika u nosicielek mutacji NOD2. Materiał i metoda: Do badania włączono 257 nieselekcjonowane chore z rakiem jajnika. Wykonano oznaczenia mutacji 3020insC w genie NOD2. Zebrano dane z historii chorób dotyczące wieku zachorowania, rozpoznania histopatologicznego, stopnia klinicznego zaawansowania nowotworu wg FIGO i stopnia morfologicznej złośliwości G. Wyniki: Mutację 3020insC w genie NOD2 badano u 257 pacjentek. Zmianę wykryto u 19 kobiet uzyskując częstość 7,39%. Nie wykazano podwyższenia ryzyka rozwoju raka jajnika dla nosicielek mutacji NOD2 (OR=1,01; 95%CI=0,61-1,66; p=0,928). średnia wieku zachorowania dla nosicielek mutacji NOD2 wynosiła 54,8 (SD=9,9) w porównaniu do 53,2 (SD=10,2) dla chorych bez mutacji. Różnica częstości nie była istotna statystycznie (p=0,550). Dokonano charakterystyki patologiczno-klinicznej raka jajnika. Ocenie poddano wiek zachorowania, typ histologiczny nowotworu, stopień morfologicznej złośliwości G i stopień zaawansowania wg FIGO. Nie znaleziono istotnych statystycznie cech nowotworu charakterystycznych dla nosicielek mutacji w genie NOD2. Wnioski: 1. Pomimo wysokiej częstości wyst´powania mutacji konstytucyjnych w genie NOD2 w grupie kobiet chorych na raka jajnika nie wydaje się zasadne wykonywanie testu u wszystkich chorych z tym nowotworem. 2. Z powodu braku podwyższonego ryzyka rozwoju raka jajnika u nosicielek mutacji w genie NOD2 postępowanie w stosunku do nich może nie odbiegać od rekomendacji dla populacji ogólnej. 3. Trudno jest określić charakterystyczne cechy patologiczno-kliniczne raka jajnika dla nosicielek mutacji NOD2

Diagnostyka prenatalna rzadkich zaburzeń rozwojowych płodu – opis przypadku

Abstract Hereby we present a case of a pregnancy in which careful dysmorphology of the fetus in subsequent sonographic evaluation resulted in detection of a very rare anomaly. It allowed explanation of the fetal phenotype, compared then with that of the newborn and estimation of genetic risk for the next pregnancies in this family.Streszczenie Przedstawiono przypadek ciąży, w której dzięki wnikliwej analizie dysmorfologicznej płodu w kolejnych badaniach USG zainicjowano szereg unikalnych badań genetycznych, które doprowadziły do wykrycia bardzo rzadkiego zaburzenia u dziecka. Pozwoliło to wyjaśnić zarówno fenotyp płodu, następnie żywo urodzonego dziecka, jak i ocenić ryzyko genetyczne występujące w tej rodzinie w kolejnych ciążach

Genetic contribution to all cancers: the first demonstration using the model of breast cancers from Poland stratified by age at diagnosis and tumour pathology

The aim of the study is to verify the hypothesis that genetic polymorphisms are associated with the predisposition to all malignancies. Using as a model breast cancers from the homogenous Polish population (West Pomeranian region) after stratification of 977 patients by age at diagnosis (under 51 years and above 50 years) and by tumour pathology (ductal cancers––low and high grade, lobular cancers, ER-positive/negative) we tested this hypothesis. Altogether 20 different groups of breast cancer cases have been analyzed. The results were compared to a group of unaffected controls that were matched by age, sex, ethnicity and geographical location and originated from families without cancers of any site among relatives. Molecular alterations selected for analyses included those which have been previously recognized as being associated with breast cancer predisposition. Statistically significant differences between the breast cancer cases and controls were observed in 19 of the 20 analyzed groups. Genetic changes were present in more than 90% of the breast cancer patients in 18 of 20 groups. The highest proportion of cases with constitutional changes—99.3% (139/140) was observed for lobular cancers. The number and type of genetic marker and/or the level of their association with the specific cancer predisposition was different between groups. Markers associated with majority of groups included: BRCA1, CHEK2, p53, TNRnTT, FGFRnAA, XPD CC/AA and XPD GG. Some markers appeared to be group specific and included polymorphisms in CDKN2A, CYP1B1, M3K nAA, and RS67

Common alleles in candidate susceptibility genes associated with risk and development of epithelial ovarian cancer

Common germline genetic variation in the population is associated with susceptibility to epithelial ovarian cancer. Microcell-mediated chromosome transfer and expression microarray analysis identified nine genes associated with functional suppression of tumorogenicity in ovarian cancer cell lines; AIFM2, AKTIP, AXIN2, CASP5, FILIP1L, RBBP8, RGC32, RUVBL1 and STAG3. Sixty-three tagging single nucleotide polymorphisms (tSNPs) in these genes were genotyped in 1,799 invasive ovarian cancer cases and 3,045 controls to look for associations with disease risk. Two SNPs in RUVBL1, rs13063604 and rs7650365, were associated with increased risk of serous ovarian cancer [HetOR = 1.42 (1.15–1.74) and the HomOR = 1.63 (1.10–1.42), p-trend = 0.0002] and [HetOR = 0.97 (0.80–1.17), HomOR = 0.74 (0.58–0.93), p-trend = 0.009], respectively. We genotyped rs13063604 and rs7650365 in an additional 4,590 cases and 6,031 controls from ten sites from the United States, Europe and Australia; however, neither SNP was significant in Stage 2. We also evaluated the potential role of tSNPs in these nine genes in ovarian cancer development by testing for allele-specific loss of heterozygosity (LOH) in 286 primary ovarian tumours. We found frequent LOH for tSNPs in AXIN2, AKTIP and RGC32 (64, 46 and 34%, respectively) and one SNP, rs1637001, in STAG3 showed significant allele-specific LOH with loss of the common allele in 94% of informative tumours (p = 0.015). Array comparative genomic hybridisation indicated that this nonrandom allelic imbalance was due to amplification of the rare allele. In conclusion, we show evidence for the involvement of a common allele of STAG3 in the development of epithelial ovarian cancer

A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2

Epithelial ovarian cancer has a major heritable component, but the known susceptibility genes explain less than half the excess familial risk1. We performed a genome wide association study (GWAS) to identify common ovarian cancer susceptibility alleles. We evaluated 507,094 SNPs genotyped in 1,817 cases and 2,353 controls from the UK and ~2 million imputed SNPs. We genotyped the 22,790 top ranked SNPs in 4,274 cases and 4,809 controls of European ancestry from Europe, USA and Australia. We identified 12 SNPs at 9p22 associated with disease risk (P<10−8). The most significant SNP (rs3814113; P = 2.5 × 10−17) was genotyped in a further 2,670 ovarian cancer cases and 4,668 controls confirming its association (combined data odds ratio = 0.82 95% CI 0.79 – 0.86, P-trend = 5.1 × 10−19). The association differs by histological subtype, being strongest for serous ovarian cancers (OR 0.77 95% CI 0.73 – 0.81, Ptrend = 4.1 × 10−21)

A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2.

Epithelial ovarian cancer has a major heritable component, but the known susceptibility genes explain less than half the excess familial risk. We performed a genome-wide association study (GWAS) to identify common ovarian cancer susceptibility alleles. We evaluated 507,094 SNPs genotyped in 1,817 cases and 2,353 controls from the UK and approximately 2 million imputed SNPs. We genotyped the 22,790 top ranked SNPs in 4,274 cases and 4,809 controls of European ancestry from Europe, USA and Australia. We identified 12 SNPs at 9p22 associated with disease risk (P < 10(-8)). The most significant SNP (rs3814113; P = 2.5 x 10(-17)) was genotyped in a further 2,670 ovarian cancer cases and 4,668 controls, confirming its association (combined data odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.79-0.86, P(trend) = 5.1 x 10(-19)). The association differs by histological subtype, being strongest for serous ovarian cancers (OR 0.77, 95% CI 0.73-0.81, P(trend) = 4.1 x 10(-21))