Dujo Kovacević

University Clinical Hospital Center "Sestre Milosrdnice", Zagrabia, Grad Zagreb, Croatia

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Publications (12)72.75 Total impact

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    ABSTRACT: Twenty common genetic variants have been associated with risk of developing colorectal cancer (CRC) in genome wide association studies to date. Since large differences between populations exist, generalisability of findings to any specific population needs to be confirmed. THE AIM OF THIS STUDY WAS TO PERFORM AN ASSOCIATION STUDY BETWEEN RISK VARIANTS: rs10795668, rs16892766, rs3802842 and rs4939827 and CRC risk in Croatian population. An association study was performed on 320 colorectal cancer cases and 594 controls recruited in Croatia. We genotyped four variants previously associated with CRC: rs10795668, rs16892766, rs3802842 and rs4939827. SMAD7 variant rs4939827 (18q21.1) was significantly associated with CRC risk in Croatian population. C allele was associated with a decreased risk, odds ratio (OR): 0.70 (95% CI: 0.57-0.85, P=3.5E-04). Compared to TT homozygotes, risk was reduced by 34% in heterozygotes (OR=0.66, 95% CI: 0.47-0.92) and by 52% in CC homozygotes (OR=0.48, 95% CI: 0.33-0.72). Our results show association of rs4939827 with colorectal cancer risk in Croatian population. The higher strength of the association in comparison to other studies suggests population-specific environmental or genetic factors may be modifying the association. More studies are needed to further describe role of rs4939827 in CRC. Likely reason for failure of replication for other 3 loci is inadequate study power.
    Full-text · Article · Sep 2013 · PLoS ONE
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    ABSTRACT: Background: Detection of circulating cancer cells by reverse transcription polymerase chain reaction (RT-PCR) has been studied as a prognostic marker in patients with colorectal cancer (CRC) but so far with conflicting results regarding specificity and prognostic value. In this study cytokeratin-20 (CK20) was evaluated by real-time RT-PCR as a marker for circulating CRC cell detection and the influence of surgical tumor resection on the presence of circulating CRC cells was analyzed. Methods: RNA was isolated from the mononuclear cell fraction of blood samples taken from 95 CRC patients before and after tumor resection and from 23 healthy volunteers and assayed by real-time RT-PCR for CK20 expression. Results: Among 23 healthy volunteers one was positive for CK20. Among 95 CRC patients, 25 were positive for CK20 before and 23 after surgery. Sixteen patients positive before surgery became negative after surgery, while 14 patients negative before surgery became positive after surgery. An increase in the proportion of CK20-positive samples with increasing stage of disease was observed for preoperative but not postoperative blood samples. Conclusions: Its association with clinical stage indicates that CK20 might have prognostic value as a marker for detection of circulating CRC cells. Surgical tumor resection can both reduce and induce the presence of circulating CRC cells.
    No preview · Article · Apr 2013 · The International journal of biological markers
  • I. Samija · J. Lukac · M. Koncar-Mubrin · I. Kirac · D. Kovacevic · Z. Kusic

    No preview · Article · Jul 2012

  • No preview · Article · May 2012 · Nature Genetics
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    ABSTRACT: We performed a meta-analysis of five genome-wide association studies to identify common variants influencing colorectal cancer (CRC) risk comprising 8,682 cases and 9,649 controls. Replication analysis was performed in case-control sets totaling 21,096 cases and 19,555 controls. We identified three new CRC risk loci at 6p21 (rs1321311, near CDKN1A; P = 1.14 × 10(-10)), 11q13.4 (rs3824999, intronic to POLD3; P = 3.65 × 10(-10)) and Xp22.2 (rs5934683, near SHROOM2; P = 7.30 × 10(-10)) This brings the number of independent loci associated with CRC risk to 20 and provides further insight into the genetic architecture of inherited susceptibility to CRC.
    Full-text · Article · May 2012 · Nature Genetics
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    ABSTRACT: To estimate the incidence and mortality trends of gastric and colorectal cancers in Croatia between 1988 and 2008. Incidence data for the period 1988-2008 were obtained from the Croatian National Cancer Registry. The number of deaths from gastric and colorectal cancers were obtained from the World Health Organization mortality database. Joinpoint regression analysis was used to describe changes in trends by sex. Gastric cancer incidence rates declined steadily during the study period, with estimated annual percent change (EAPC) of -3.2% for men and -2.8% for women. Mortality rates in men decreased, with EAPC of -5.0% from 1988-1995 and -2.5% from 1995-2008. Mortality rates in women decreased, with EAPC of -3.2% throughout the study period. For colorectal cancer in men, joinpoint analysis revealed increasing trends of both incidence (EAPC 2.9%) and mortality (EAPC 2.1%). In women, the increase in incidence was not significant, but mortality rates in the last 15 years showed a significant increase (EAPC 1.1%). The incidence and mortality trends of gastric cancer in Croatia are similar to other European countries, while the still increasing colorectal cancer mortality calls for more efficient prevention and treatment.
    Full-text · Article · Apr 2012 · Croatian Medical Journal
  • J. Lukac · D. Kovacevic · I. Samija · I. Kirac · Z. Kusic
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    ABSTRACT: Purpose: To determine the usefulness of reverse transcriptase-polymerase chain reaction (RT-PCR) recognition of cytokeratin 20-encoding mRNA in assessing the extent of preoperative and intraoperative hematogenic tumor cell dissemination in patients with colorectal cancer undergoing primary tumor resection. Methods: Circulating tumor cells (CTC) were determined using conventional RT-PCR in preoperative peripheral venous blood of 65, intraoperative peripheral venous blood of 45, and mesenteric venous blood of 36 patients with colorectal cancer, and in peripheral venous blood of 21 healthy volunteers. Results: Positive findings were obtained in preoperative blood of 17% of AJCC stage 0-III vs. 56% stage IV pts (p=0.007), in mesenteric blood of 18% stage 0-III vs. 89% stage IV pts (p<0.001), and in none of the healthy volunteers. Among patients with liver metastases, positive resultswere found in 37.5% peripheral blood and in 100% mesenteric blood samples (p=0.063). 17% patients with negative preoperative findings became intraoperatively positive (p=0.031). Conclusion: Positive CTC findings in preoperative peripheral venous blood correlate to the clinical stage of the disease in colorectal cancer patients. CTC determination in mesenteric venous blood seems to be more indicative for liver metastases than their detection in preoperative peripheral venous blood. Surgical manipulation facilitates the dissemination of tumor cells by circulation.
    No preview · Article · Jan 2011
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    ABSTRACT: Gallstone ileus with impaction of gallstone in distal duodenum is an extremely rare complication of cholecystolithiasis. Gallstone ileus in itself accounts for less than 1% of these complications with 800 cases described so far. However, there are less than 15 cases described with the impaction of gallstone in distal duodenum. We report a case of an 84-year-old male patient in whom gallstone impacted in distal duodenum was found by ultrasonography and confirmed by computed tomography. Cholecystitis and a remaining large gallstone in the gallbladder were found intraoperatively, which made us opt for one-step procedure, i.e. lithotomy and fistula repair with cholecystectomy. Due to the rare position of impacted gallstone, we believe that cases like this should be reported in detail in order to generate enough data for establishing optimal treatment options.
    Full-text · Article · Sep 2010 · Acta clinica Croatica
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    ABSTRACT: The aim of this study was to analyze microphthalmia-associated transcription factor (MITF) as a marker for the detection of circulating melanoma cells, determine its prognostic value in melanoma patients, and compare it with tyrosinase. Blood samples from 201 melanoma patients in all stages of the disease and 40 healthy volunteers were analyzed. RNA was isolated from mononuclear cell fraction of the blood and assayed by reverse transcription-PCR for the expression of MITF and tyrosinase. All samples from healthy volunteers were negative for both MITF and tyrosinase. Out of 201 blood samples from melanoma patients 32 were positive for MITF, 20 for tyrosinase, and four for both MITF and tyrosinase. Analysis of MITF as an additional marker to tyrosinase allowed for detection of circulating melanoma cells in a larger number of melanoma patients in comparison to tyrosinase analysis alone (48 vs. 20 positive). A positive value of MITF was associated with shorter progression-free (P=0.005) and overall survival (P=0.042). A positive value of tyrosinase was associated with shorter overall survival (P=0.012), whereas there was no significant association between the value of tyrosinase and progression-free survival. The value of MITF was selected with multivariate analysis as the independent prognostic factor for progression-free survival, whereas the only independent prognostic factor for overall survival was the stage of disease. This study has shown that MITF is a specific marker for detection of circulating melanoma cells that has a prognostic value in melanoma patients. Determination of MITF in addition to tyrosinase improved the detection of circulating melanoma cells in melanoma patients.
    No preview · Article · Mar 2010 · Melanoma research
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    ABSTRACT: Soluble c-erbB-2 oncoprotein has been proven as a useful marker in the management of breast cancer patients, but its value in diagnostics and follow-up of colorectal cancer patients remains controversial. The aim of this study was to evaluate the usefulness of serum c-erbB-2 monitoring in diagnostics and prediction of disease outcome in rectal cancer patients. Serum samples from 88 patients with rectal adenocarcinoma before surgery and from 41 healthy controls were tested for the presence of c-erbB-2 oncoprotein by ELISA, and the patients were followed up for at least 5 years after the surgery. Preoperative serum c-erbB-2 levels were significantly higher in stage IV patients than in healthy controls (P<0.001) and did not show correlation with preoperative CEA levels. Elevated preoperative serum c-erbB-2 levels showed relatively high specificity (88%) and low sensitivity (44%) in the diagnosis of rectal cancer. Elevated preoperative oncoprotein levels were predictive neither for overall survival nor for development of local recurrence/distant metastases. Although preoperative serum c-erbB-2 levels were significantly higher in rectal cancer patients than in healthy controls, the soluble c-erbB-2 does not seem to be useful in the diagnosis of rectal cancer due to its low sensitivity. Preoperative serum levels of this oncoprotein were predictive neither for overall survival nor for local recurrence/distant metastases in rectal cancer patients.
    Preview · Article · Jul 2007 · International Journal of Colorectal Disease
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    ABSTRACT: The total number of 542 patients with colorectal cancer surgery have been analyzed in order to estimate the effect of receiving transfusion local recurrences, and the disease free - survival. It should be examined whether there are changes in general immunity indicators which would be connected with perioperative transfusion. A significant connection has been found between local recurrences and blood transfusion (p<0.0001), the most noticeable being in Dukes A (p =0.045), localization on rectum (p=0.036). The receiving of blood transfusion is linked significantly with disease free - survival reduction (p =0.0068; log rank), the most significant being in Dukes A stage (p =0.0123; log rank) and with localization on rectum (p=0.0231). The analysis of general immunity indicators has shown significant immunocompromitation of patients just before the surgery and this could have effect on immunomodulation caused by transfusion and just as on the treatment prognosis of colorectal carcinoma.
    Full-text · Article · Jan 2007 · Collegium antropologicum
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    ABSTRACT: Overexpression of p53 protein in malignancies induces an immune response in some cancer patients. We investigated whether production of serum antibodies against p53 (p53-Ab) is associated with pathohistological parameters of colorectal carcinoma and whether p53-Ab can serve as a tumor marker during cancer treatment. Serum samples from 220 colorectal cancer patients during surgery and adjuvant chemotherapy and 42 healthy controls were tested for the presence of p53-Ab by ELISA. Expression of p53 protein in tumors was determined using mouse anti-human p53-Ab. Serum p53-Ab were detected in 18% of patients while all controls were negative. A strong correlation between p53-Ab production and p53 protein expression was observed: 70% of p53-Ab positive cases had tumors positive for p53 vs. 52% of p53-Ab negative cases. There was also a significant predominance of p53-Ab positive cases in Dukes' stages B and C over stage A. Although surgery alone reduced p53-Ab levels, decreases in p53-Ab titer became significant midterm through chemotherapy compared to both pre- and postoperative values and remained decreased until the completion of treatment. The presence of p53-Ab in sera of patients with colorectal cancer indicates tumors in more advanced histopathologic stages (Dukes' B, C). Due to low sensitivity (18%) p53-Ab are not recommendable as a preoperative marker for colorectal cancer. However, due to high specificity (100%), their monitoring after surgery and adjuvant chemotherapy has potential for early diagnosis of tumor relapse in p53-Ab positive cases.
    No preview · Article · Apr 2004 · International Journal of Colorectal Disease

Publication Stats

215 Citations
72.75 Total Impact Points

Institutions

  • 2010-2013
    • University Clinical Hospital Center "Sestre Milosrdnice"
      • Department of Oncology and Nuclear Medicine
      Zagrabia, Grad Zagreb, Croatia
  • 2007
    • Sisters of Charity Hospital Zagreb
      • Department of Oncology and Nuclear Medicine
      Zagreb - Centar, Grad Zagreb, Croatia