Povezanost OGG1 Ser326Cys polimorfizma i razina 8-OHdG u mokraći sa sklonosti obolijevanju od karcinoma pluća: rezultati ispitivanja na bolesnicima i kontrolnoj populaciji u Turskoj

High incidence and poor prognosis of lung cancer make it a major health problem worldwide. Although smoking is a major cause of lung cancer, only some smokers develop lung cancer, which suggests that there is a genetic predisposition in some individuals. 8-OHG is an important oxidative base lesion and may elevate due to cancer and smoking. It is repaired by 8-hydroxyguanine DNA glycosylase 1 (OGG1), which has several polymorphisms. Although the Ser326Cys polymorphism is consistently associated with a range of cancers, findings about this polymorphism and lung cancer risk are contradictory. To date, no study has examined this association in the Turkish population. We conducted a case-control study to investigate the association between OGG1 Ser326Cys polymorphism and the risk of lung cancer using PCR-RFLP. We also evaluated gene-smoking interaction and excretion of urinary 8-OHdG. Our results suggest that the OGG1 Ser326Cys polymorphism is not a genetic risk factor for lung cancer, and that the heterozygous genotype is associated with a significantly reduced risk for lung cancer. The levels of 8-OHdG did not correlate with the polymorphism and smoking. Larger association studies are needed to validate our findings, and mechanistic studies are needed to elucidate the underlying molecular mechanisms of this association.Karcinom pluća velik je javnozdravstveni problem u čitavom svijetu zbog svoje visoke učestalosti i loše prognoze. Premda je navika pušenja jedan od glavnih uzročnika karcinoma pluća, od ove bolesti oboli samo dio populacije pušača, što govori u prilog postojanju genetske predispozicije za njezin nastanak. 8-OHG je oksidativno oštećenje baze u molekuli DNA čija se učestalost može povećati zbog zloćudnih tumora i pušenja. U popravku tog oštećenja sudjeluje enzim 8-hidroksigvanin DNA-glikozilaza (OGG1) za koji je dokazano postojanje polimorfizma. Iako se polimorfizam Ser326Cys često dovodi u vezu s različitim vrstama zloćudnih bolesti, dosadašnji su rezultati o vezi izme|u polimorfizma tog enzima i rizika od pojave karcinoma pluća kontradiktorni. Do danas na turskoj populaciji nisu provedena istraživanja koja bi dala jasne odgovore o toj povezanosti. Ovo je istraživanje usporedo provedeno u bolesnika i u zdravoj populaciji primjenom metode PCR-RFLP s ciljem utvrđivanja moguće povezanosti polimorfizma OGG1 Ser326Cys i rizika od karcinoma pluća. Nadalje, istražena je interakcija gena i navike pušenja te ekskrecija 8-OHdG u mokraći. Dobiveni rezultati pokazuju da polimorfizam OGG1 Ser326Cys nije genetski čimbenik rizika od pojave karcinoma pluća, a pokazalo se da je heterozigotni genotip povezan sa značajno nižim rizikom od karcinoma pluća. Razine 8-OHdG izmjerene u mokraći nisu bile u korelaciji ni s polimorfizmom ni s navikom pušenja. Zaključujemo da su za vrednovanje dobivenih rezultata potrebna istra`ivanja na još većem broju ispitanika te mehanistička istraživanja koja bi mogla razjasniti molekularne mehanizme koji su u pozadini ove povezanosti

UFT plus Oral Folinic Acid with Alternating Oral and Intravenous Vinorelbine in Patients with Metastatic Breast Cancer Previously Treated with Anthracyclines and Taxanes

Background: We retrospectively evaluated the activity and toxicity of uracil/tegafur (UFT) plus oral folinic acid in combination with vinorelbine (alternating intravenous (IV) on day 1 and oral on day 8) in patients with metastatic breast cancer. Patients and Methods: Treatment consisted of IV vinorelbine 25 mg/m(2) on day 1 and 60 mg/m(2) orally on day 8, and oral UFT 300 mg/m(2) plus leucovorin 60 mg/m(2) on days 1-14 with 21 days interval. All patients were refractory to anthracyclines and taxanes. Results: Partial response (PR) was observed in 3 (9.7%) and stable disease (SD) was observed in 13 (41.9%) patients. Total clinical benefit (PR + SD) of the combination was 51.6%. The median response duration was 3 (range 1-11.8) months. Median overall survival was 9.8 months (95% confidence interval (CI): 7.5-12.1), and median time to progression was 3.4 months (95% CI: 2.3-4.5). The most common toxicities were hematologic, including 4 (12.9%) cases of grade 3 neutropenia and 4 (12.9%) cases of grade 4 neutropenia. Grade 3 diarrhea was reported in 2 (3.2%) patients. 3 (9.7%) patients had hand-foot syndrome. Febrile neutropenia was observed in 1 patient. Conclusions: Although the combination is safe and convenient in clinical practice, it has only moderate activity in metastatic breast cancer patients

Epidemiology and survival of hepatocellular carcinoma in Turkey: Outcome of multicenter study

Objective: Hepatocellular cancer (HCC) is one of the important health problems in Turkey. We aimed to determine the clinical and demographic features of HCC in the Turkish population and to evaluate the prognostic and survival features

Risk Factors of Nasopharyngeal Carcinoma in Turkey - an Epidemiological Survey of the Anatolian Society of Medical Oncology

Background: Nasopharyngeal carcinoma is a rare disease in most parts of the world with a multifactorial etiology involving an interaction of genetic, viral, environmental and dietary risk factors. This is the first epidemiologic study aimed to evaluate the risk factors of nasopharyngeal carcinoma in the Turkish population. Methods: We conducted a multicentric, retrospective, case-control study using a standardized questionnaire which captured age, sex, occupation, household type, blood group, dietary habits, smoking, alcohol consumption and oral hygiene. The study included 183 cases and 183 healthy controls matched by sex and age. Multiple logistic regression and univariate analysis were employed. Results: The peak age incidence was 40-50 years and the male to female ratio was 2:1. We observed significant associations between elevated nasopharyngeal carcinoma risk and low socioeconomic status, rural household type (OR: 3.95, p0.05); furthermore salty foods had a borderline p value (OR: 2.14, p=0.053). Blood type A increased the risk (OR: 2.03, p=0.002) while blood type 0 was a protective factor (OR: 0.53, p=0.009). Rare habit of teeth brushing (OR: 6.17, p= 10 decayed teeth before diagnosis (OR: 2.17, p<0.001) increased the risk. Conclusions: The nasopharyngeal carcinoma risk factors described in the literature are also applicable for the Turkish population. People with type A blood are at risk in Turkey. Salted foods have also a border risk out of the endemic regions. This is the only study showing that poor oral hygene is a serious risk factor for nasopharyngeal carcinoma

Progression-free survival of patients according to LPI.

<p>Progression-free survival of patients according to LPI.</p

Results of univariate and multivariate Cox's proportional hazard models regarding OS.

<p><i>OS</i> overall survival, <i>HR</i> hazard ratio, <i>CI</i> confidence interval, <i>LPI</i> laboratory prognostic index, <i>ECOG</i> Eastern Cooperative Oncology Group, <i>PS</i> performance status, <i>WBC</i> White Blood Cell count, <i>LDH Lactate dehydrogenase, ALP</i> Alkaline phosphatase.</p><p>Results of univariate and multivariate Cox's proportional hazard models regarding OS.</p

Vinorelbine in Combination with Carboplatin followed by Single-agent Consolidation Therapy for Unresectable Localized or Metastatic Non-small-cell Lung Carcinomas

Background: Adding more than four cycles of the combination regimen increase toxicities. The availability of an intravenous (i.v.) and oral form of vinorelbine appeared as a particularly convenient way to provide a consolidation treatment to patients who have achieved an objective response or stable disease. Patients and methods: This study was retrospectively designed to investigate the efficacy in terms of response and safety of i.v. vinorelbine 25 mg/m(2) on day 1 and oral vinorelbine 60 mg/m(2) on day 8 given with carboplatin area under the curve (AUC) 5 once every 3 weeks (q3w) for four cycles followed by consolidation therapy with single-agent vinorelbine in non-progressive patients with advanced non-small-cell lung cancer (NSCLC). Results: Seventy-two patients enrolled into the study from October 2006 to July 2009 received the combination regimen. Thirty-seven patients (51.3%) also received the subsequent consolidation treatment. Partial tumor responses were obtained in 25 patients (34.7%) of 72 evaluable patients. Stable disease was observed in 26 (36.1%) of patients. The median progression free-survival was 4 months (95% CI 3.1-4.8). The median overall survival time was 10 months (95% CI 8.2-11.7) and the 1 year survival was 38.1%. The main toxicities recorded were hematological. Grade 3-4 neutropenia were observed in 17 patients (23.6%). Only two patients experienced grade three febrile neutropenia in the induction period, and there was no occurrence of febril neutropenia in the consolidation period. Nausea and vomiting were the major non-hematological toxicities reported. Toxicities occurred primarily during the initial combination phase of the chemotherapy. Conclusions: Despite the low dose of vinorelbine (25mg/m(2) i.v. on day 1 and only 60 mg/m(2) oral on day 8, every 3 weeks) achieved during the study, the response rate of 34.7%, the disease control of 70.8% and the 10 months median overall survival with tolerable toxicity profile, confirmed that this combination, offers an active and safe regimen for patients with advanced NSCL