Nurzhan Turmanov

Hannover Medical School, Hanover, Lower Saxony, Germany

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Publications (7)18.23 Total impact

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    ABSTRACT: Bloom's syndrome is a rare autosomal recessive chromosomal instability disorder with a high incidence of various types of neoplasia, including breast cancer. Whether monoallelic BLM mutations predispose to breast cancer has been a long-standing question. A nonsense mutation, p.Q548X, has recently been associated with an increased risk for breast cancer in a Russian case-control study. In the present work, we have investigated the prevalence of this Slavic BLM founder mutation in a total of 3,188 breast cancer cases and 2,458 controls from Bashkortostan, Belarus, Ukraine, and Kazakhstan. The p.Q548X allele was most frequent in Russian patients (0.8 %) but was also prevalent in Byelorussian and Ukrainian patients (0.5 and 0.6 %, respectively), whereas it was absent in Altaic or other non-European subpopulations. In a combined analysis of our four case-control series, the p.Q548X mutation was significantly associated with breast cancer (Mantel-Haenszel OR 5.1, 95 % CI 1.2; 21.9, p = 0.03). A meta-analysis with the previous study from the St. Petersburg area corroborates the association (OR 5.7, 95 % CI 2.0; 15.9, p = 3.7 × 10(-4)). A meta-analysis for all published truncating mutations further supports the association of BLM with breast cancer, with an estimated two- to five-fold increase in risk (OR 3.3, 95 %CI 1.9; 5.6, p = 1.9 × 10(-5)). Altogether, these data indicate that BLM is not only a gene for Bloom's syndrome but also might represent a breast cancer susceptibility gene.
    Breast Cancer Research and Treatment 12/2012; · 4.47 Impact Factor
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    ABSTRACT: BACKGROUND: Experimental and epidemiological evidence have suggested that chronic inflammation may play a critical role in endometrial carcinogenesis. METHODS: To investigate this hypothesis, a two-stage study was carried out to evaluate single nucleotide polymorphisms (SNPs) in inflammatory pathway genes in association with endometrial cancer risk. In stage 1, 64 candidate pathway genes were identified and 4,542 directly genotyped or imputed SNPs were analyzed among 832 endometrial cancer cases and 2,049 controls, using data from the Shanghai Endometrial Cancer Genetics Study. Linkage disequilibrium of stage 1 SNPs significantly associated with endometrial cancer (P<0.05) indicated that the majority of associations could be linked to one of 24 distinct loci. One SNP from each of the 24 loci was then selected for follow-up genotyping. Of these, 21 SNPs were successfully designed and genotyped in stage 2, which consisted of ten additional studies including 6,604 endometrial cancer cases and 8,511 controls. RESULTS: Five of the 21 SNPs had significant allelic odds ratios and 95% confidence intervals as follows: FABP1, 0.92 (0.85-0.99); CXCL3, 1.16 (1.05-1.29); IL6, 1.08 (1.00-1.17); MSR1, 0.90 (0.82-0.98); and MMP9, 0.91 (0.87-0.97). Two of these polymorphisms were independently significant in the replication sample (rs352038 in CXCL3 and rs3918249 in MMP9). The association for the MMP9 polymorphism remained significant after Bonferroni correction and showed a significant association with endometrial cancer in both Asian- and European-ancestry samples. CONCLUSIONS: These findings lend support to the hypothesis that genetic polymorphisms in genes involved in the inflammatory pathway may contribute to genetic susceptibility to endometrial cancer. Impact: This study adds to the growing evidence that inflammation plays an important role in endometrial carcinogenesis.
    Cancer Epidemiology Biomarkers &amp Prevention 12/2012; · 4.56 Impact Factor
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    ABSTRACT: Genome-wide association studies (GWAS) have identified more than 100 genetic loci for various cancers. However, only one is for endometrial cancer. We conducted a three-stage GWAS including 8,492 endometrial cancer cases and 16,596 controls. After analyzing 585,963 single-nucleotide polymorphisms (SNP) in 832 cases and 2,682 controls (stage I) from the Shanghai Endometrial Cancer Genetics Study, we selected the top 106 SNPs for in silico replication among 1,265 cases and 5,190 controls from the Australian/British Endometrial Cancer GWAS (stage II). Nine SNPs showed results consistent in direction with stage I with P < 0.1. These nine SNPs were investigated among 459 cases and 558 controls (stage IIIa) and six SNPs showed a direction of association consistent with stages I and II. These six SNPs, plus two additional SNPs selected on the basis of linkage disequilibrium and P values in stage II, were investigated among 5,936 cases and 8,166 controls from an additional 11 studies (stage IIIb). SNP rs1202524, near the CAPN9 gene on chromosome 1q42.2, showed a consistent association with endometrial cancer risk across all three stages, with ORs of 1.09 [95% confidence interval (CI), 1.03-1.16] for the A/G genotype and 1.17 (95% CI, 1.05-1.30) for the G/G genotype (P = 1.6 × 10(-4) in combined analyses of all samples). The association was stronger when limited to the endometrioid subtype, with ORs (95% CI) of 1.11 (1.04-1.18) and 1.21 (1.08-1.35), respectively (P = 2.4 × 10(-5)). Chromosome 1q42.2 may host an endometrial cancer susceptibility locus. This study identified a potential genetic locus for endometrial cancer risk.
    Cancer Epidemiology Biomarkers &amp Prevention 03/2012; 21(6):980-7. · 4.56 Impact Factor
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    ABSTRACT: BACKGROUND AND OBJECTIVES:: Prostate cancer has a genetic component, and single nucleotide polymorphisms (SNPs) can contribute to the risk. We aimed to investigate the role of polymorphisms in 10 candidate genes with a key function in apoptosis. METHODS AND MATERIALS:: Eight coding SNPs were chosen in ATM (Ser49Cys), BID (Ser56Cys), CASP8 (Asp302His), CASP10 (Val410Ile), LGALS3 (Pro64His), RASSF1 (Ser133Ala), TP53 (Arg72Pro), and TP53AIP1 (Ala7Val), and two non-coding SNPs were selected in BCL2 (-938C/A) and HDM2 (SNP309). A hospital-based case-control series of 510 prostate cancer patients and 490 healthy males from Northern Germany were genotyped for these polymorphisms. RESULTS:: SNP rs4644 in LGALS3 showed evidence for a protective effect of the minor allele, encoding the His64 variant (OR 0.82, 95% CI 0.69;0.99, P = 0.04). Carriers were underrepresented among cases under a dominant model (OR 0.71; 95% CI 0.54;0.92; P = 0.01), and the effect appeared more pronounced in patients diagnosed before the age of 60 years (OR 0.52; 95% CI 0.31;0.85, P = 0.01). The other nine polymorphisms did not vary significantly between cases and controls, though subtle trends were noted for BCL2 (P = 0.07) and CASP10 (P = 0.08). The Asp302His variant of CASP8 tended to associate with a protective effect in the group with higher Gleason score under a dominant model (P = 0.03). Carriers of either the CASP8 or the CASP10 variants were underrepresented in the prostate cancer series (P = 0.02). CONCLUSIONS:: These results provide first evidence to implicate the functional Pro64His variant of galectin-3 (LGALS3) in the genetic susceptibility towards prostate cancer. The potential role of polymorphisms in BCL2, CASP8, and CASP10 merits further investigation.
    Urologic Oncology 03/2011; · 3.65 Impact Factor
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    ABSTRACT: despite the improved quality of diagnostic technology, myocardial infarction still belongs to the diseases that are most frequently overlooked. Especially asymptomatic patients or patients with atypical symptoms are more common to be misdiagnosed. Failure to correctly diagnose is the leading cause of malpractice claims. It was the aim of this study to evaluate the records of patients who died from myocardial infarction and to analyse whether medical malpractice had occured in those who had undergone a medical examination shortly before their death. in the years 2008 and 2009 myocardial infarction had been diagnosed in 109 auotopsies performed at the Institute of Legal Medicine of the Hanover Medical School. The records of these patients who had died from myocardial infarction were retrospectively analysed with particular emphasis on an antemortem medical consultation, reported symptoms and diagnostic measures. in 38 persons (34.9 %) an antemortem medical consultation or hospitalisation has taken place, whereby in five persons the diagnosis of myocardial infarction was suspected. In 33 persons, a myocardial infarction could not be diagnosed antemortem. In two cases an additionally cardiologic assessment was recommended to estimate if medical malpractice was present and in another two cases with insufficient diagnostic measures medical malpractice was reproached from forensic pathologists. autopsy give the most accurate diagnostic information. On the other hand, it may provide an effective defence against medical malpractice litigation.
    DMW - Deutsche Medizinische Wochenschrift 12/2010; 135(49):2451-5. · 0.65 Impact Factor
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    ABSTRACT: Acute aortic dissection is a life-threatening disease with a high rate of mortality. The dissection of the artery with a distal blood flow can explain the variable and changeable symptoms. Aortic dissections require immediate diagnosis and therapy. In the Institute of Legal Medicine of the Hannover Medical School, 34 cases of aortic dissection were found during autopsy between 2006 and 2009. The cases were analysed retrospectively. In the majority of cases (55.9%) an antemortem medical consultation has taken place. In only one case an aortic dissection could be diagnosed at a later time. Key in the management of acute aortic dissection is to maintain a high clinical index of suspicion for this diagnosis. Etiologically hereditary diseases (Marfan syndrome, Ehlers-Danlos syndrome, Loeys-Dietz syndrome) should be taken into consideration as a possible cause. In all unexpected deaths of young adults an autopsy should be performed to detect the cause of death and for genetic testing to provide information for the relatives in case an aortic aneurysm can be found.
    Medizinische Klinik 12/2010; 105(12):871-5. · 0.34 Impact Factor
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    ABSTRACT: Hintergrund und Ziel: Akute Aortendissektionen stellen eine lebensbedrohliche Erkrankung mit einer hohen Mortalitätsrate dar. Durch eine Spaltbildung der aortalen Wandschichten mit nach distal fortschreitender Wühlblutung können eine Vielzahl von unterschiedlichen und wechselhaften Symptomen auftreten. Aortendissektionen erfordern eine unverzügliche Diagnosestellung und Therapie. Methodik: Am Institut für Rechtsmedizin der Medizinischen Hochschule Hannover wurden in den Jahren 2006 bis 2009 34 Verstorbene mit einem Aneurysma dissecans obduziert. Die Fälle wurden retrospektiv analysiert. Ergebnisse: Die Mehrzahl der verstorbenen Personen (55,9%) hatte unmittelbar vor dem Tod einen Arzt aufgesucht. Nur in einem Fall konnte ein disseziierendes Aortenaneurysma verspätet diagnostiziert werden. Schlussfolgerung: Ein hohes Maß an klinischem Verdacht auf das Vorliegen einer Aortendissektion ist für die richtige Diagnosefindung erforderlich. Ursächlich kommen auch hereditäre Erkrankungen (Marfan-Syndrom, Ehlers- Danlos-Syndrom, Loeys-Dietz-Syndrom) in Betracht. Bei allen ungeklärten Todesfällen von jungen Erwachsenen sollte eine Obduktion durchgeführt werden, um die Todesursache zu klären und im Falle einer vorliegenden Aortendissektion eine genetische Testung und Information der Familienmitglieder vornehmen zu können. Background and Purpose: Acute aortic dissection is a life-threatening disease with a high rate of mortality. The dissection of the artery with a distal blood flow can explain the variable and changeable symptoms. Aortic dissections require immediate diagnosis and therapy. Methods: In the Institute of Legal Medicine of the Hannover Medical School, 34 cases of aortic dissection were found during autopsy between 2006 and 2009. The cases were analysed retrospectively. Results: In the majority of cases (55.9%) an antemortem medical consultation has taken place. In only one case an aortic dissection could be diagnosed at a later time. Conclusion: Key in the managment of acute aortic dissection is to maintain a high clinical index of suspicion for this diagnosis. Etiologically hereditary diseases (Marfan syndrome, Ehlers-Danlos syndrome, Loeys-Dietz syndrome) should be taken into consideration as a possible cause. In all unexpected deaths of young adults an autopsy should be performed to detect the cause of death and for genetic testing to provide information for the relatives in case an aortic aneurysm can be found. Schlüsselwörter: Aneurysma dissecans–Aortenaneurysma–Fehldiagnose–Obduktion–Heriditäre Erkrankungen Key Words: Aortic dissection–Aneurysm–Misdiagnosis–Autopsy–Genetic syndromes
    105(12):871-875.