Cancer Predisposition Cascade Screening for Hereditary Breast/Ovarian Cancer and Lynch Syndromes in Switzerland: Study Protocol.

BACKGROUND: Breast, colorectal, ovarian, and endometrial cancers constitute approximately 30% of newly diagnosed cancer cases in Switzerland, affecting more than 12,000 individuals annually. Hundreds of these patients are likely to carry germline pathogenic variants associated with hereditary breast ovarian cancer (HBOC) or Lynch syndrome (LS). Genetic services (counseling and testing) for hereditary susceptibility to cancer can prevent many cancer diagnoses and deaths through early identification and risk management. OBJECTIVE: Cascade screening is the systematic identification and testing of relatives of a known mutation carrier. It determines whether asymptomatic relatives also carry the known variant, needing management options to reduce future harmful outcomes. Specific aims of the CASCADE study are to (1) survey index cases with HBOC or LS from clinic-based genetic testing records and determine their current cancer status and surveillance practices, needs for coordination of medical care, psychosocial needs, patient-provider and patient-family communication, quality of life, and willingness to serve as advocates for cancer genetic services to blood relatives, (2) survey first- and second-degree relatives and first-cousins identified from pedigrees or family history records of HBOC and LS index cases and determine their current cancer and mutation status, cancer surveillance practices, needs for coordination of medical care, barriers and facilitators to using cancer genetic services, psychosocial needs, patient-provider and patient-family communication, quality of life, and willingness to participate in a study designed to increase use of cancer genetic services, and (3) explore the influence of patient-provider communication about genetic cancer risk on patient-family communication and the acceptability of a family-based communication, coping, and decision support intervention with focus group(s) of mutation carriers and relatives. METHODS: CASCADE is a longitudinal study using surveys (online or paper/pencil) and focus groups, designed to elicit factors that enhance cascade genetic testing for HBOC and LS in Switzerland. Repeated observations are the optimal way for assessing these outcomes. Focus groups will examine barriers in patient-provider and patient-family communication, and the acceptability of a family-based communication, coping, and decision-support intervention. The survey will be developed in English, translated into three languages (German, French, and Italian), and back-translated into English, except for scales with validated versions in these languages. RESULTS: Descriptive analyses will include calculating means, standard deviations, frequencies, and percentages of variables and participant descriptors. Bivariate analyses (Pearson correlations, chi-square test for differences in proportions, and t test for differences in means) will assess associations between demographics and clinical characteristics. Regression analyses will incorporate generalized estimating equations for pairing index cases with their relatives and explore whether predictors are in direct, mediating, or moderating relationship to an outcome. Focus group data will be transcribed verbatim and analyzed for common themes. CONCLUSIONS: Robust evidence from basic science and descriptive population-based studies in Switzerland support the necessity of cascade screening for genetic predisposition to HBOC and LS. CASCADE is designed to address translation of this knowledge into public health interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT03124212; https://clinicaltrials.gov/ct2/show/NCT03124212 (Archived by WebCite at http://www.webcitation.org/6tKZnNDBt).

The vitamin D system is deregulated in pancreatic diseases.

The vitamin D system is deregulated during development and progression of several cancer types. Data on the expression of the vitamin D system in the diseased pancreas are missing. The aim of this study was to investigate the expression of the vitamin D receptor (VDR), 1,25-dihydroxyvitamin D3 24-hydroxylase (CYP24A1), and the calcium-sensing receptor (CaSR), a vitamin D target gene, in the different regions of the pancreas in patients with chronic pancreatitis (n=6) and pancreatic ductal adenocarcinomas (PDAC) (n=17). We analyzed the expression of these genes at mRNA and protein level with quantitative real-time RT-PCR and immunostaining. mRNA expression of CYP24A1 and VDR was significantly increased in tumors compared with the adjacent non-tumorous tissue (p<0.01), while CaSR mRNA expression decreased. Both the VDR and the CaSR protein were highly expressed in the endocrine compared with the exocrine pancreas. In CP the CYP24A1 expression was highest in the endocrine pancreas, while in PDACs in the transformed ducts. In the PDAC patients CYP24A1 expression in the islets was significantly lower than in CP patients. Our data suggest that during ductal adenocarcinoma development the vitamin D system in the pancreas becomes deregulated on two levels: in the islets CYP24A1 expression decreases weakening the negative feedback regulation of the vitamin D-dependent insulin synthesis/secretion. In the transformed ducts CYP24A1 expression increases, impairing the antiproliferative effect of vitamin D in these cells.

CYP24A1 inhibition facilitates the anti-tumor effect of vitamin D3 on colorectal cancer cells.

AIM: The effects of vitamin D3 have been investigated on various tumors, including colorectal cancer (CRC). 25-hydroxyvitamin-D3-24-hydroxylase (CYP24A1), the enzyme that inactivates the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 (1,25-D3), is considered to be the main enzyme determining the biological half-life of 1,25-D3. During colorectal carcinogenesis, the expression and concentration of CYP24A1 increases significantly, suggesting that this phenomenon could be responsible for the proposed efficacy of 1,25-D3 in the treatment of CRC. The aim of this study was to investigate the anti-tumor effects of vitamin D3 on the human CRC cell line Caco-2 after inhibition of the cytochrome P450 component of CYP24A1 activity. METHODS: We examined the expression of CYP24A1 mRNA and the effects of 1,25-D3 on the cell line Caco-2 after inhibition of CYP24A1. Cell viability and proliferation were determined by means of sulforhodamine-B staining and bromodeoxyuridine incorporation, respectively, while cytotoxicity was estimated via the lactate dehydrogenase content of the cell culture supernatant. CYP24A1 expression was measured by real-time reverse transcription polymerase chain reaction. A number of tetralone compounds were synthesized to investigate their CP24A1 inhibitory activity. RESULTS: In response to 1,25-D3, CYP24A1 mRNA expression was enhanced significantly, in a time- and dose-dependent manner. Caco-2 cell viability and proliferation were not influenced by the administration of 1,25-D3 alone, but were markedly reduced by co-administration of 1,25-D3 and KD-35, a CYP24A1-inhibiting tetralone. Our data suggest that the mechanism of action of co-administered KD-35 and 1,25-D3 does not involve a direct cytotoxic effect, but rather the inhibition of cell proliferation. CONCLUSION: These findings demonstrate that the selective inhibition of CYP24A1 by compounds such as KD-35 may be a new approach for enhancement of the anti-tumor effect of 1,25-D3 on CRC.

[Obstetrical and gynecological relevance of inflammatory bowel disease]. / A gyulladásos bélbetegségek szülészeti-nogyógyászati vonatkozásai.

INTRODUCTION: Inflammatory bowel disease may show a life long persistence, while female fertility is time-limited. AIM: The aim of the authors was to obtain more knowledge about the obstetrical-gynecological aspects of this disorder. METHODS: The authors evaluated 100 patients with inflammatory bowel disease and 100 healthy women with a self-composed questionnaire. RESULTS: Menarche occurred significantly earlier in patients than in controls (p = 0,03). Either the activity of the disease, or the therapy itself may initiate irregularities in the menstrual cycle. Patients used contraceptives less frequently than controls (p = 0,002), and the time from family-planning to conception was longer in patients. Symptoms of bowel disease during pregnancy were not as severe as before and after pregnancy (p<0,001). Excess weight had a beneficial effect on symptoms during pregnancy (p = 0,042) and on the frequency of complications. Preterm birth and low birth weight were more frequent in newborns of patients (p = 0,019). CONCLUSION: Pregnancy has positive effect on the symptoms of inflammatory bowel disease in case gestation occurs in a stable period of the inflammatory bowel disease.

Marked increase of CYP24A1 mRNA level in hepatocellular carcinoma cell lines following vitamin D administration.

AIM: 1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) inhibits cell growth and induces apoptosis in numerous types of tumors. We aimed to examine the mRNA and protein expression of 1,25(OH)(2)D(3)-inactivating CYP24A1 and mRNA expression of the activating CYP27B1 enzymes, as well as that of vitamin D receptor (VDR), in hepatocellular carcinoma (HCC) cell cultures in response to 1,25(OH)(2)D(3) administration. MATERIALS AND METHODS: Increasing amounts of 1,25(OH)(2)D(3) (0.256-10 nM) were added to cultures of HepG2, Huh-Neo, Hep3B, Huh5-15 human HCC cell lines and cells then incubated for various time periods (30 min-28 h). The mRNA expression was analyzed by real time reverse transcription-polymerase chain reaction (RT-PCR). CYP24A1 protein in HepG2 cells was detected by immuncytochemistry. RESULTS: CYP24A1 mRNA expression significantly (p<0.0001) increased in response to 1,25(OH)(2)D(3) administration in two cell lines: in HepG2 cells, the CYP24A1 mRNA level exhibited 5,300-fold elevation, reaching a maximum value at 8 h; in Huh-Neo cells, the increase was 152-fold that of the baseline value, with the maximum being reached at 14 h. There was no significant change in Hep3B and Huh5-15 cell lines, nor was there any change in CYP27B1 and VDR gene expression in any cell cultures. Immuncytochemistry in HepG2 cells proved that gene activation was followed by CYP24A1 protein synthesis. CONCLUSION: Our novel data indicate that administration of 1,25(OH)(2)D(3) results in a marked increase of CYP24A1 mRNA expression in some, but not all, human HCC lines in vitro. These differences could be dependent upon the origin of the tumor cells.

[Verner-Morrison syndrome: a case study]. / Verner-Morrison-szindróma egy esete.

Verner and Morrison described a syndrome of watery diarrhea, hypokalemia, and achlorhydria (WDHA) in 1958. VIPomas producing high amounts of vasoactive intestinal peptide (VIP) commonly originate from the pancreas. Typical symptoms play a momentous role in the diagnosis of VIPoma. Diarrhea may persist for years before the diagnosis. Morbidity from untreated WDHA syndrome is associated with long-standing dehydration and with electrolyte and acid-base metabolism disorders, which may cause chronic renal failure. Assessment of specific marker (VIP) offers high sensitivity in establishing the diagnosis. Imaging modalities include endoscopic ultrasonography, computed tomography and magnetic resonance imaging, and particularly, scintigraphy with somatostatin analogues. Treatment options include resection of the tumor, chemotherapy or the reduction of symptoms with somatostatin analogues. Early diagnosis and management may affect survival of patients favorably. VIPoma cases may be associated with multiple endocrine neoplasia type 1.

Double-balloon endoscopy for small intestinal disease: a single-center experience in Hungary.

BACKGROUND: We report on our experience with the Fujinon EN-450 T5 therapeutic double-balloon endoscope (DBE) and compare our findings with the results of earlier capsule endoscopy. MATERIAL/METHODS: Between August 2005 and July 2009, 150 DBE procedures were conducted in 139 consecutive patients (M/F: 67/72, age: 51.1 years, SD: 18.6 years) who presented at our tertiary referral hospital. The results of previous capsule endoscopy (CE) examinations were available in 27 patients. The indications for DBE included obscure gastrointestinal bleeding (OGIB) in 83 patients, suspected/known IBD in 25, and polyposis/suspected neoplasia in 29 patients. All of the examinations were performed at our outpatient clinic. RESULTS: In OGIB, abnormal small-bowel findings were noted in 50 patients (60.2%) including angiodysplasias, erosions, and small ulcers. Malignancy was found in 6 patients (7.2%), while an intervention was carried out in 24 patients. In suspected IBD cases, IBD was diagnosed in 5/13 cases. In known IBD patients, assessment of the extent as well as disease behavior and activity was the indication. In polyposis/suspected malignancy, polyps were removed by snare polypectomy in 8 Peutz-Jeghers patients, while primary adenocarcinoma was diagnosed in 4. The concordance of CE and DBE findings was 51.8% (14/27), while in 2 cases DBE provided significantly new information, including 1 malignancy. The average insertion length was app. 213 cm (range: 70-480 cm). CONCLUSIONS: Based on our experience, DBE is a safe and useful method for evaluating and treating small-bowel disease in selected patients with obscure bleeding, IBD or polyposis syndromes. The concordance of DBE and CE in this real-life setting was only fair.

The candidate oncogene CYP24A1: A potential biomarker for colorectal tumorigenesis.

The main autocrine/paracrine role of the active metabolite of vitamin D(3), 1alpha,25-dihydroxyvitamin D(3) (1,25-D(3)), is inhibition of cell growth and induction of cell differentiation and/or apoptosis. Synthesis and degradation of the secosteroid occurs not only in the kidney but also in normal tissue or malignant extrarenal tissues such as the colon. Because 25-hydroxyvitamin D(3) 24-hydroxylase (CYP24A1) is considered to be the main enzyme determining the biological half-life of 1,25-D(3), we have examined expression of the CYP24A1 mRNA (by real-time RT-PCR) and protein (by immunohistochemistry) in normal human colon mucosa, colorectal adenomas, and adenocarcinomas in 111 patients. Although 76% of the normal and benign colonic tissue was either completely devoid of or expressed very low levels of CYP24A1, in the majority of the adenocarcinomas (69%), the enzyme was present at high concentrations. A parallel increased expression of the proliferation marker Ki-67 in the same samples suggests that overexpression of CYP24A1 reduced local 1,25-D(3) availability, decreasing its antiproliferative effect.

The 3'UTR NFKBIA variant is associated with extensive colitis in Hungarian IBD patients.

PURPOSE: In previous studies the NFKBIA 3'UTR (untranslated region) AA genotype was associated with Crohn's disease (CD), while the NFKB1-94ins/delATTG mutation increased the risk for ulcerative colitis (UC). The aim of our study was to investigate these two polymorphisms and patients' response to medical therapy and/or disease phenotype in Hungarian inflammatory bowel disease (IBD) patients. METHODS: NFKBIA 3'UTR- and NFKB1-94ins/delATTG polymorphisms were investigated in 415 unrelated IBD patients (CD: 266 patients, mean age 35.2 +/- 12.1 years, duration 8.7 +/- 7.5 years; UC patients: 149, mean age 44.4 +/- 15.4 years, duration 10.7 +/- 8.9 years) and 149 controls by PCR-restriction fragment length polymorphism (RFLP) analysis. Detailed clinical phenotypes were determined by reviewing the medical charts. RESULTS: The NFKBIA 3'UTR and NFKB1-94ins/delATTG genotypes and allele frequencies were not significantly different among IBD and controls. In patients with UC, the 3'UTR GG genotype was associated with extensive colitis (55.3 vs. 29.4%, odds ratio 2.97, 95% confidence interval 1.45-6.08). The presence of variant alleles did not predict response to steroids, infliximab, or need for surgery. CONCLUSIONS: The NFKBIA 3'UTR GG genotype was associated with an increased risk for extensive colitis in Hungarian patients. In contrast, variant alleles did not predict response to medical therapy or need for surgery.

Effects of the lactase 13910 C/T and calcium-sensor receptor A986S G/T gene polymorphisms on the incidence and recurrence of colorectal cancer in Hungarian population.

BACKGROUND: Epidemiological studies suggested the chemopreventive role of higher calcium intake in colorectal carcinogenesis. We examined genetic polymorphisms that might influence calcium metabolism: lactase (LCT) gene 13910 C/T polymorphism causing lactose intolerance and calcium-sensing receptor (CaSR) gene A986S polymorphism as a responsible factor for the altered cellular calcium sensation. METHODS: 538 Hungarian subjects were studied: 278 patients with colorectal cancer and 260 healthy controls. Median follow-up was 17 months. After genotyping, the relationship between LCT 13910 C/T and CaSR A986S polymorphisms as well as tumor incidence/progression was investigated. RESULTS: in patient with colorectal cancer, a significantly higher LCT CC frequency was associated with increased distant disease recurrence (OR = 4.04; 95% CI = 1.71-9.58; p = 0.006). The disease free survival calculated from distant recurrence was reduced for those with LCT CC genotype (log rank test p = 0.008). In case of CaSR A986S polymorphism, the homozygous SS genotype was more frequent in patients than in controls (OR = 4.01; 95% CI = 1.33-12.07; p = 0.014). The number of LCT C and CaSR S risk alleles were correlated with tumor incidence (p = 0.035). The CCSS genotype combination was found only in patients with CRC (p = 0.033). CONCLUSION: LCT 13910 C/T and CaSR A986S polymorphisms may have an impact on the progression and/or incidence of CRC.

Double-balloon enteroscopy for the diagnosis and treatment of obscure bleeding, inflammatory bowel diseases and polyposis syndromes: we see more but do we know more?

BACKGROUND/AIMS: Our aim was to report our experience with the Fujinon EN-450 T5 therapeutic double-balloon endoscope (DBE) in the diagnosis of small bowel diseases. METHODOLOGY: Between August 2005 and October 2006, 52 DBE procedures were conducted on 47 consecutive patients (M/F: 22/25, age: 51.6 SD 19.5 years) presenting at our tertiary referral hospital (35 and 7 patients from oral and anal route, respectively; 5 patients from both). All procedures were performed using i.v. anesthesia, at our outpatient clinic. RESULTS: Indication suspected small-bowel bleeding in 28 patients, suspected/known inflammatory bowel syndrome (IBD) in 12 and polyposis/suspected neoplasia in 7. In obscure bleeding small-bowel abnormality was found in 18 patients (64.3%) including angiodysplasias/erosions and one polypoid lesion. In suspected IBD, IBD was diagnosed in 2 out of 8 cases. In patients with polyposis syndromes, polyps were in two Peutz-Jeghers patients, while a further patient with suspected stenosis was diagnosed with primary adenocarcinoma. The average insertion length was app. 213cm. No severe complications were observed. CONCLUSIONS: Based on our experience DBE is a safe and useful method for evaluating and treating small bowel disease in selected patients with obscure bleeding, IBD or polyposis syndromes, however the clinical importance of minute lesions still needs to be determined.

[Impact of CYP3A7*1C polymorphism on bone mineral content in postmenopausal women]. / A CYP3A7*1C-polimorfizmus hatása a csont ásványanyag-tartalmára posztmenopauzás nokben.

INTRODUCTION: CYP3A7*1C polymorphism has been shown to be associated with lower levels of serum dehydroepiandrosterone sulphate in men. The age-related decline of dehydroepiandrosterone sulphate levels is believed to contribute to the development of osteoporosis. We hypothesized that CYP3A7*1C may lead to bone loss through decreased levels of dehydroepiandrosterone sulphate in postmenopausal women. PATIENTS AND METHODS: 319 postmenopausal women were studied and divided into two subgroups: 217 women with osteoporosis and 102 aged-matched women without osteoporosis. The CYP3A7*1C polymorphism was genotyped. Serum dehydroepiandrosterone sulphate levels and bone mineral density were measured. RESULTS: Homozygous CYP3A7*1C carriers had significantly lower bone mineral density at lumbar spine than that of wild type (T-score with CYP3A7*1C mutant type: -3.27 +/- 1.02, T-score with wild type: -1.35 +/- 1.53, p = 0.041) after adjusting for age and DHEAS levels. No association was found between genotypes and dehydroepiandrosterone sulphate levels. CONCLUSION: Our data suggest that CYP3A7 polymorphism might have an influence on bone mass at the lumbar spine independently of serum dehydroepiandrosterone sulphate concentrations.

[Significance of dehydroepiandrosterone and dehydroepiandrosterone sulfate in different diseases]. / A dehidroepiandroszteron és dehidroepiandroszteron-szulfát jelentôsége különbözo kórállapotokban.

Dehydroepiandrosterone and dehydroepiandrosterone-sulfate are precursors of androgens and estrogens, support the gonadal sexual steroid production. The levels of dehydroepiandrosterone and dehydroepiandrosterone-sulfate are maximal between the ages of 20 and 30 years, then start a decline of 2% per year, leaving a residual of 10-20% of the peak production by the eight decade of life. The age-associated decrease may lead to osteoporosis, deterioration of lipid-metabolism, cardiovascular diseases and second type of diabetes mellitus. Decreased levels were found in autoimmune diseases and in sexual dysfunction, too. Intracrinology describes the formation of active hormones which exert their action in the same cells where synthesis took place without release into the pericellular compartment. The high local androgen and estrogen concentration may be important in the pathomechanism of hirsutism, acne, seborrhea, breast and prostate cancer. Administration of dehydroepiandrosterone resulted in a reduction of postmenopausal osteoporosis, also the decreased symptoms in systemic lupus erythematosis, psychiatric diseases and sexual disfunction. The authors summarize the metabolism of dehydroepiandrosterone and dehydroepiandrosterone-sulfate and their role in different diseases.

[Double-balloon endoscopy for the diagnosis and treatment of small intestinal disease: an initial experience from 25 examinations]. / A kettos ballonos endoszkópia szerepe a vékonybél betegségeinek diagnózisában és kezelésében: kezdeti tapasztalataink az elso 25 vizsgálat során.

UNLABELLED: Until recently, only the proximal small bowel was accessible for diagnostic and therapeutic endoscopy. Endoscopic evaluation of this organ has often required open laparotomy with surgically assisted passage of the endoscope through the intestine. Recently, Yamamoto et al have developed a new method, double-balloon endoscopy (DBE) that allows high-resolution visualization and therapeutic interventions in all segments of the GI tract. Our aim was to report our early experience with the Fujinon EN-450 T5 therapeutic double-balloon endoscope. PATIENTS AND METHODS: Between August 2005 and March 2006, 25 DBE was conducted in 23 consecutive patients (M/F: 13/10, age: 51.8 +/- 16.5 years) presenting at our tertiary referral hospitals (17 and 4 patients from the oral or the anal route, respectively; 2 patients from both). All procedures were done by i.v. anesthesia, at our outpatient clinic. After the procedure, the patients were monitored in a recovery room for at least 4h before discharge. RESULTS: The main indication for DBE was suspected small-bowel GI bleeding (11), diagnosis or complications of IBD (7), polyposis syndrome (3), stenosis (1) and insertion of jejunal catheter in one case. Twelve out of 22 patients (54.5%) had a small-bowel finding, with 16 of 22 (72.7%) of the patients having a more accurate diagnostic input. The average insertion length was app. 165 cm (range 50-350 cm, SD 97). Patients' tolerance of the procedure was excellent. No severe complications were recognized. CONCLUSIONS: Based on our limited experience double-balloon enteroscopy is a safe and useful method to evaluate and treating small bowel disease in selected patients, including patients with suspected small-bowel strictures, in whom capsule endoscopy is contraindicated.

Location and age at onset of colorectal cancer in Hungarian patients between 1993 and 2004. The high number of advanced cases supports the need for a colorectal cancer screening program in Hungary.

BACKGROUND: In recent decades, the incidence of proximal colorectal cancer (CRC) in North America and Western Europe has steadily increased, while that of the distal tumors has shown a corresponding decrease. Our aim was to investigate the change in age at diagnosis, the gender, location and cancer stage of CRC cases over the last 12 years in a large number of Hungarian patients. PATIENTS AND METHODS: The clinical and histological data of 1694 CRC patients (M/F: 917/777, age at diagnosis: 65.2 +/- SD 12.5 years), diagnosed at the First Department of Medicine and the First Department of Surgery of Semmelweis University, Budapest, Hungary, between January 1, 1993 and December 31, 2004, were analyzed retrospectively. RESULTS: CRCs were rectal or left-sided in 70% and proximal (transverse, ascending or cecum) in 30% of the cases. The proportion of rectal carcinomas increased over the observed period (1993-1998: 31.6% vs. 1999-2004: 42.1%, p=0.001), while the proportion of proximal tumors remained stable. Eleven percent of CRCs were diagnosed under the age of 50 years. The age at diagnosis did not differ between males and females, but was lower in patients with rectal tumors compared to other localizations (p=0.02); 75.7% of the CRCs were T3-T4 at diagnosis and lymph node metastases could be detected in 47.7%. CONCLUSION: In contrast to Western European and North American trends, the proportion of proximal CRCs did not increase in Hungary over the observed period. Almost two-thirds of all cancers were left-sided. The high percentage of locally advanced tumors and lymph node metastases supports the need for colorectal screening programs.

[Change in location of colorectal cancer in Hungarian patients between 1993-2004]. / A colorectalis rákok lokalizációjának változása Magyarországon 1993 és 2004 között.

UNLABELLED: The incidence of proximal tumours in Western countries has steadily increased while that of distal tumours has shown a corresponding decrease. Our aim was to investigate the prevalence, location and histology of colorectal cancers in the last twelve years in Hungarian patients. PATIENTS AND METHODS: Clinical data of 1738 patients diagnosed with colorectal tumors (M/F: 940/798, mean age at diagnosis: 65.2 +/- 12.5 years) between 1st of January 1993 and 31st of December 2004 at the 1st Internal Medicine and 1st Surgery Department of Semmelweis University were enrolled. Pathology and clinical data were analysed retrospectively. The observed periods were the following 1993-1998 and 1999-2004. RESULTS: 1694 (97.5%) of the patients had adenocarcinoma (CRC), 15 anaplastic cancers, 9 carcinoid, 6 planocellular, 5 GIST, 3 leiomyoma and 2-2 melanoma, lymphoma and shigillocellular cancers were diagnosed. 75.7% (943/1246) of the CRCs were diagnosed at locally advanced stage (T3-T4), and 47.7% (521/1093) of CRC patients had lymph node metastasis at the time of diagnosis. 11.0% of the CRCs were diagnosed in <50 year-olds (<40 years: 2.5%, <30 years: 0.5%). The location of the CRC was distal in 1186 (rectum: 53.9%, sigmoid/descending: 46.1) and proximal in 508 cases. Synchronous cancers were detected in 12 patients (age: 68.8 +/- 11.6 years, gender: 11 male/1 female, location: rectum and transverse in 6, rectum and ascending/caecum in 5 patients). Age at diagnosis was not different according to gender (M/F: 64.8 +/- 12.0 years vs. 65.8 +/- 12.9 years), but it was lower in patients with rectal cancer compared to left or right sided cancers (64.1 years vs. left: 66.1 years, right: 66.0 years, p = 0.02). Rectal CRC was more common in males, while the proportion of proximal cancers was lower (rectum, M/F: 41.2% vs. 33.5%, proximal M/F: 26.8% vs. 33.8%, p = 0.003). The proportion of rectal cancers increased over the observed period (1993-1998: rectal: 31.6% vs. 1999-2004: 42.1%, p = 0.002). CONCLUSIONS: In contrast to Western countries, the proportion of proximal CRC did not become higher in Hungary. Still more than two-third of the patients were diagnosed to have distal cancers. The proportion of male patients was higher in this subset of CRC. The high percentage of locally advanced and metastatic cancers supports the need for colorectal screening program in Hungary.

Relationship between serum calcium and CA 19-9 levels in colorectal cancer.

AIM: To examine the calcium metabolism of colorectal cancer (CRC) in patients with colorectal cancer and control patients. METHODS: Seventy newly diagnosed CRC patients were included. The healthy control group was age and gender matched (n=32). Particular attention was devoted to the relationship between serum calcium of patients, and levels of AFP, CEA, carbohydrate antigen 19-9 (CA 19-9) (that could be considered as prognostic factors). Furthermore, the Ca-sensing receptor (CaSR) gene A986S polymorphism was investigated in these patients, as well as the relationship between different CaSR genotypes and the data stated above. RESULTS: A lower level of ionized calcium (also corrected for albumin) was found in the serum of CRC patients with normal 25(OH) vitamin D levels. The ionized calcium concentration was inversely correlated with the serum level of CA 19-9. There was no difference in the distribution of CaSR genotypes, between CRC patients and general population. The genotypes did not correlate with other data examined. CONCLUSION: Based on these results, lower levels of serum calcium might be a pathogenic and prognostic factor in colorectal cancer.