Xanthomicrol Exerts Antiangiogenic and Antitumor Effects in a Mouse Melanoma (B16F10) Allograft Model.

Xanthomicrol, a trimethoxylated hydroxyflavone, is the main active component of Dracocephalum kotschyi Boiss leaf extract. Preliminary in vitro studies identified this compound as a potential antiangiogenic and anticancer agent. This study aimed to evaluate in vivo anticancer effect of xanthomicrol and investigate its molecular mechanism of action in a mouse melanoma (B16F10) model. Effect of xanthomicrol on B16F10 melanoma cell viability was determined using the MTT assay. For in vivo experiments, C57BL/6 mice were inoculated subcutaneously with B16F10 cells. After five days, once daily administration of xanthomicrol, thalidomide, or vehicle was commenced and continued for 21 consecutive days. On the 26th day, blood samples and tumor biopsies were taken for subsequent molecular analysis. Xanthomicrol showed inhibitory effect on viability of B16F10 melanoma cells (IC50 value: 3.433 µg/ml). Initial tumor growth, tumor volume and weight, and angiogenesis were significantly decreased in xanthomicrol-treated animals compared with those in vehicle group. Protein expression of phosphorylated Akt, mRNA expressions of HIF-1α and VEGF in tumor tissues, and serum VEGF were significantly decreased in xanthomicrol-treated animals compared with vehicle-treated animals. Thus, xanthomicrol inhibited cancer cell growth both in vitro and in vivo. This effect, at least in part, was exerted by interfering with PI3K/Akt signaling pathway and inhibiting VEGF secretion by tumor cells. Further studies are required to elucidate the exact molecular mechanisms of antitumor activity of xanthomicrol.

A potential clinical significance of DAB2IP and SPRY2 transcript variants in prostate cancer.

Deregulation of key signaling pathways is one of the primary phenomena in carcinogenesis. DAB2IP and SPRY2 are regulatory elements, which act as feedback inhibitors of receptor tyrosine kinases signaling in mitogen-activated protein kinase pathway. These elements have also been implicated in the pathophysiology of cancer. Therefore, this study is aimed to investigate the expression of all known splice variants of DAB2IP and SPRY2 in prostate tissue. Fresh Prostate tissue samples (50 prostate cancer/ matched normal tissue and 30 BPH) were collected and total RNA was extracted followed by cDNA synthesis. The expression of DAB2IP and SPRY2 transcript variants were evaluated using RT-PCR and quantitative Real-time PCR. The results indicated significant down-regulation of DAB2IP transcript variant 1 in cancerous tissues compared to paired normal tissues (P = 0.001) as well as SPRY2 transcript variant 2 in cancerous tissues in comparison with the normal counterparts and BPH (P = 0.008 and P = 0.025, respectively). In addition, there was a significant negative correlation between DAB2IP.1 and SPRY2.2 expression with PSA levels in prostate cancer (P = 0.039 ρ =-0.24 and P = 0.045 ρ =-0.3, respectively). Interestingly, the down-regulation of DAB2IP.1 mRNA and SPRY2.2 mRNA was positively correlated in tumor samples (P = 0.002 ρ = 0.434). For the first time, this experiment highlights the deregulation of DAB2IP and SPRY2 transcript variants in human prostate cancer. The present study confirms and extends the previous reports through indicating transcript-specific down-regulation and significant association of DAB2IP and SPRY2 in prostate tumorigenesis.

Squamous cell carcinoma (SCC) arising in esophageal colon interposition.

The idea of using the colon to replace a resected esophagus has a long history. The colon has become a favored organ for esophageal reconstruction in adults with esophageal cancer when the stomach is not suitable or is unavailable. In this article, we introduce an 84-year-old woman that she had surgery 40 years ago and presented with an invasive well differentiated squamous cell carcinoma of colonic origin in reconstructed esophagus.

MicroRNA-146a induces immune suppression and drug-resistant colorectal cancer cells.

Recent studies underline the involvement of microRNAs in cancer development through induction of immune suppression milieu and evolution of drug resistance. The goal of this study was to evaluate the effects of miR-146a on regulatory T cells' frequencies, T-lymphocyte proliferation, and cytokine expression as well as drug resistance in cancer cells. We found that miR-146a was overexpressed in colon cancer HT-29 cells. Peripheral blood mononuclear cells were obtained from healthy donors and were co-cultured with transfected HT-29 cells. Afterward, peripheral blood mononuclear cell proliferation, expression of anti-inflammatory cytokines, and regulatory T cells' frequencies were assayed. Also, drug resistance in transfected HT-29 cells was analyzed following treatment with 5-fluorouracil and irinotecan. Overexpression of miR-146a increased transforming growth factor-ß and interleukin-10 expressions and enhanced regulatory T cells' frequencies in peripheral blood mononuclear cells. Also, the number of cells undergoing cell cycle arrest and apoptosis significantly decreased in transfected HT-29 cancer cells. In conclusion, upregulation of miR-146a plays an important role in enhancing immune suppression through increasing the regulatory T cells' population. Also, our data indicated that colon cancer drug resistance is possibly associated with miR-146a overexpression.

Association between Pattern of Gastritis and Gastroesophageal Reflux Disease in Patients with Helicobacter Pylori Infection.

BACKGROUND Reflux disease is a common gastrointestinal problem. The association between reflux disease and gastritis pattern is controversial. AIM: To determine the association between reflux disease and gastritis pattern in patients with Helicobacter pylori (H. pylori) infection. METHODS 470 patients with dyspepsia and reflux disease were enrolled in this study. The inclusion criteria were willing to participate in the study, age over 40 years, and having the criteria of ROME III for at least 3 months. Patients with history of H. pylori eradication therapy during the 3 months before the study, a history of gastric surgery, and gastric cancer were excluded. All of the participants underwent upper endoscopy and two biopsy samples were taken from antrum, body, and fundal areas. RESULTS H. pylori infection rate was 367 (78.1%) with mean age of 59.8 ± 11.4 years. Of them 131 patients (35.7%) were male. Reflux disease was detected in 273 (74.4%) patients. 216 (58.9%) and 102 (27.8%) patients had non-erosive reflux disease (NERD) and gastroesophageal reflux disease (GERD), respectively. Corpus predominant and antral predominant gastritis were seen in 72 (19.6%) and 129 (35.2%) patients, respectively. Antral gastritis was significantly associated with GERD (p<0.01). In regression analysis, antral predominant gastritis had a significant association with GERD (OR=1.92; 95%CI: 1.22- 3.12). The same result was observed in mild to moderate antral and greater curvature gastritis (OR= 1.26; 95%CI: 0.25-6.40 and OR= 3.0; 95%CI: 0.63-14.17, respectively). CONCLUSION According to these finding ,we could suggest that the pattern of gastritis could be associated with reflux disease and GERD.

Accuracy of endoscopic ultrasonography for determination of tumor invasion depth in gastric cancer.

BACKGROUND: Gastric cancer (GC) is one the common lethal cancers in Iran. Detection of GC in the early stages would assesses to improve the survival of patients. In this study, we attempt to evaluate the accuracy of EUS in detection depth of invasion of GC among Iranian Patients. MATERIALS AND METHODS: This study is a retrospective study of patients with pathologically confirmed GC. They underwent EUS before initiating the treatment. The accuracy of EUS and agreement between the two methods was evaluated by comparing pre treatment EUS finding with post operative histopathological results. RESULTS: The overall accuracy of EUS for T and N staging was 67.9% and 75.47, respectively. Underestimation and overestimation was seen in 22 (14.2%) and 40 (25.6%) respectively. The EUS was more accurate in large tumors and the tumors located in the middle and lower parts of the stomach. The EUS was more sensitive in T3 staging. The values of weighted Kappa from the T and N staging were 0.53 and 0.66, respectively. CONCLUSIONS: EUS is a useful modality for evaluating the depth of invasion of GC. The accuracy of EUS was higher if the tumor was located in the lower parts of the stomach and the size of the tumor was more than 3 cm. Therefore, judgments made upon other criteria evaluated in this study need to be reconsidered.

Prevalence of gastric precancerous lesions among chronic dyspeptic patients and related common risk factors.

Gastric cancer is one of the leading causes of cancer-related deaths worldwide. Progression of gastric cancer follows several steps from gastritis to atrophy, intestinal metaplasia, dysplasia, and finally cancer. The aim of this study was to determine the prevalence of gastric precancerous lesions and related common risk factors in a group of chronic dyspeptic patients. A total of 688 chronic dyspeptic patients older than 40 years of age were consecutively enrolled. The exclusion criteria were pregnancy, and a history of gastric cancer and gastric surgery. A questionnaire including demographic and clinical data, smoking habits, alcohol use, NSAIDs, and regular aspirin use was completed for all patients. Upper endoscopy and gastric biopsy were performed for all of the participants according to the standard protocols. Upper endoscopy was performed for all of the participants and biopsies were taken according to the biopsy protocol. The specimens were examined in a blinded manner by two expert gastrointestinal pathologists. The mean age of the participants was 57.87±9.10 years; there were 361 (52.5%) women. The prevalence of intestinal metaplasia, gastric atrophy, dysplasia, and positive Helicobacter pylori infection was 19.8, 12.8, 3.2%, and 64.5%, respectively. Age and H. pylori infection showed a significant association with pathological findings (odds ratio=3.10, 95% confidence interval: 1.91-4.72 and odds ratio=3.56, 95% confidence interval: 2.30-5.53, respectively). According to the high prevalence of precancerous lesions in patients with chronic dyspepsia who were older than 40 years of age, upper endoscopy and gastric mapping sampling for the detection of these lesions is recommended in intermediate-risk to high-risk areas.

Prevalence of colorectal adenoma in an average-risk population aged 40-50 versus 50-60 years.

According to current guidelines, screening colonoscopy begins at 50 years for the average-risk population, although there are not enough data on the incidence of precancerous lesions of individuals in the preceding decades. To evaluate the prevalence of colorectal polyps including potentially premalignant lesions in asymptomatic, average-risk individuals aged 40-49 versus 50-59 years, we offered total colonoscopy screening to individuals without any lower gastrointestinal symptoms. The primary end point was the prevalence of colorectal adenoma in two age groups. Of a total of 737 studies, 333 participants were 40-49 years old and 407 participants were 50-59 years old. The overall prevalence of adenomas was 11.2 and 16.4% in the group of 40-49 and 50-59 year olds, respectively. Advanced adenoma was more common in 50-59 year olds (1.2 vs. 2.9%). Malignancy was not reported in these groups. Furthermore, 77.5 and 68.6% of adenomas were observed in the distal colon in the groups of 40-49 year olds and 50-59 year olds, whereas in the proximal colon, 22.2 and 57.1% of adenomas in the groups of 40-49 year olds and 50-59 year olds, respectively, were advanced adenomas. In our study, male sex showed an association with adenoma. However, importantly, there was no significant association between age and colorectal adenoma. Although the prevalence of colorectal adenoma was similar in the two age groups investigated, the rate of advanced adenoma was higher in the group of individuals who were 50-59 years old, suggesting that colorectal cancer screening could be recommended at an age younger than 50 years.

Prevalence of colorectal polyps in a group of subjects at average-risk of colorectal cancer undergoing colonoscopic screening in Tehran, Iran between 2008 and 2013.

BACKGROUND: Colorectal cancer (CRC) is one of the prime causes of mortality around the globe, with a significantly rising incidence in the Middle East region in recent decades. Since detection of CRC in the early stages is an important issue, and also since to date there are no comprehensive epidemiologic studies depicting the Middle East region with special attention to the average risk group, further investigation is of significant necessity in this regard. AIM: Our aim was to investigate the prevalence of preneoplastic and neoplastic lesions of the colon in an average risk population. MATERIALS AND METHODS: A total of 1,208 eligible asymptomatic, average- risk adults older than 40 years of age, referred to Firuzgar Hospotal in the years 2008-2012, were enrolled. They underwent colonoscopy screening and all polypoid lesions were removed and examined by an expert gastrointestinal pathologist. The lesions were classified by size, location, numbers and pathologic findings. Size of lesions was measured objectively by endoscopists. RESULTS: The mean age of participants was 56.5±9.59 and 51.6% were male. The overall polyp detection rate was 199/1208 (16.5 %), 26 subjects having non-neoplastic polyps, including hyperplastic lesions, and 173/1208 (14.3%) having neoplastic polyps, of which 26 (2.15%) were advanced neoplasms .The prevalence of colorectal neoplasia was more common among the 50-59 age group. Advanced adenoma was more frequent among the 60-69 age group. The majority of adenomas were detected in the distal colon, but a quarter of advanced adenomas were found in the proximal colon; advance age and male gender was associated with the presence of adenoma. CONCLUSIONS: It seems that CRC screening among average-risk population might be recommended in countries such as Iran. However, sigmioidoscopy alone would miss many colorectal adenomas. Furthermore, the 50-59 age group could be considered as an appropriate target population for this purpose in Iran.

Pepsinogen II can be a potential surrogate marker of morphological changes in corpus before and after H. pylori eradication.

BACKGROUND: The aim of this investigation is to study the relationship between gastric morphology and serum biomarkers before and after Helicobacter pylori eradication. METHODS: First-degree relatives of gastric cancer patients underwent gastroscopy before and 2.5 years after H. pylori eradication. The morphological changes in two categories (normal to mild and moderate to severe) were compared with level of pepsinogens I and II before eradication (n = 369), after eradication (n = 115), and in those with persistent infection (n = 250). RESULTS: After eradication, pepsinogen I decreased to 70% and pepsinogen II to 45% of the previous values. Unlike pepsinogen II and pepsinogen I to II ratio that were affected by the severity of inflammation and atrophy in corpus in all groups, pepsinogen I generally did not change. After eradication, subjects with high mononuclear infiltration in corpus had lower pepsinogen I (54 versus 77.1 µ/mL), higher pepsinogen II (9.4 versus 6.9 µ/mL), and lower ratio (7.9 versus 11.6) than those without (P < 0.05). CONCLUSION: Pepsinogen II is a good marker of corpus morphological changes before and after H. pylori eradication.

Changes in Structure, Interstitial Cajal-like Cells and Apoptosis of Smooth Muscle Cells in Congenital Ureteropelvic Junction Obstruction.

OBJECTIVE: The goal of this study is to evaluate some structural changes in muscular, collagenous and neural components as well as expression of Cajal-like cells and apoptosis of smooth muscle cells in congenital ureteropelvic junction obstruction (UPJO). METHODS: Tissue specimens were obtained from 25 patients with UPJO and compared with normal ureteropelvic junction regions of 19 autopsies. In paraffin embedded sections the amount of Cajal-like cells, density of nerve fibers and smooth muscle cell apoptosis (using immunohistochemical staining) were determined. Collagen deposition and muscular components were stained by Trichrome-Masson staining and evaluated by image analysis techniques. Arrangement of muscular bundles was also evaluated qualitatively. Findings : The number of Cajal-like cells was significantly lower in patients than in controls. The apoptotic score and mean number of nerve fibers were not statistically different for the two groups. Arrangement of muscular fibers was more irregular in patients than in controls (P<0.001). Collagen deposition was significantly higher in patients than in controls (P<0.001). The mean amount of muscular component was lower in patients than in normal ones. (P= 0.09) CONCLUSION: We found significant pathologic changes in congenital ureteropelvic junction obstruction such as decrease in Cajal-like cells, increase in collagen deposition and irregular arrangement of muscle fibers.

Bilateral wilms' tumor metastasis to right spermatic cord.

Wilms' tumor (WT) is the most common primary renal tumor in children. Common sites of metastases are lungs, liver and regional lymph nodes. Testicular and paratesticular metastasis due to WT have been reported but it is extremely rare. We report a 33-month -old male with bilateral WT and metastasis to right spermatic cord.

Mitochondrial D-Loop polymorphism and microsatellite instability in prostate cancer and benign hyperplasia patients.

In this study mitochondrial D-Loop variations in Iranian prostate cancer and benign prostatic hyperplasia (BPH) patients were investigated. Tumour samples and corresponding non-cancerous prostate tissue from 40 prostate cancer patients and 40 age-matched BPH patients were collected. The entire mtD-loop region (16024-576) was amplified using the PCR method and products were gel-purified and subjected to direct nucleotide sequencing. A total of 129 variations were found, the most frequent being 263A-G and 310T-C among both BPH and prostate cancer patients. Variation of 309 C-T was significantly more frequent in prostate cancer patients (P value<0.05). Four novel variations were observed on comparison with the MITOMAP database. Novel variations were np16154delT, np366G-A, np389G-A and 56insT. There was no correspondence between the different variations and the age of subjects. Considering that D-loop variations were frequent in both BPH and prostate cancer patients in our study, the fact that both groups had high average age can be a possible contributing factor. D-loop polymorphisms and microsatellite instability can influence cell physiology and result in a benign or malignant phenotype. Significantly higher frequency of 309 C-T variation in cancer patients is a notable finding and must be a focus of attention in future studies.

Precancerous conditions after H. pylori eradication: a randomized double blind study in first degree relatives of gastric cancer patients.

BACKGROUND: Regression of precancerous lesions after H. pylori eradication remains controversial. This study evaluates the change and topography in first degree relatives (FDR) of gastric cancer (GC) patients following H. pylori eradication. METHODS: Participants underwent endoscopy with antrum and corpus histological examinations. Subjects with pangastritis were randomly allocated to placebo or eradication therapy and followed over 4½ years.  RESULTS: Among 989 evaluated FDR, we excluded 468 patients as follows: 108 had macroscopic lesions, 243 had no evidence of any H. pylori infection, and 117 were excluded for other reasons. The remaining subjects (n = 521) were allocated to therapy (group A, n = 261) or placebo (group B, n = 260) groups. Interim analysis of 403 subjects (201 placebo, 202 therapy) showed regression of atrophy (60 out of 97 in the antrum and 37 out of 104 in the corpus) in H.pylori-eradicated versus regression of atrophy (57 out of 184 in the antrum and 23 out of 173 in the corpus) in non-H.pylori-eradicated cases over 2½ years (P < 0.0001). No regression of intestinal metaplasia (IM) occurred in the antrum and corpus of treated subjects over 4½ years. However, progression of IM occurred in the antrum in 17 out of 90 patients in the non-H. pylori-eradicated versus 4 out of 68 H. pylori-eradicated subjects after 4½ years (P < 0.05). CONCLUSION: Eradication of H. pylori is associated with regression of gastric atrophy but not IM, even in its early stages. Gastric atrophy and IM in the antrum have shown more rapid progression in cases not treated for H. pylori infection (over 4½ years follow-up) compared to H. pylori-eradicated cases.

Topography of gastritis and its severity in 864 first degree relatives of gastric cancer patients.

OBJECTIVES: Studies on gastric mucosal histological findings among first degree relatives (FDR) of gastric cancer (GC) patients are scarce. The aim is to evaluate the topography and the severity of gastritis among FDR of GC patients. DESIGN: A total of 989 subjects who were FDR of GC patients, ages 40-65 years underwent gastroscopies. When no gross lesion was found, five specimens were evaluated according to the Sydney Classification and one for urease testing in order to determine the type of gastritis and its severity. RESULTS: Of the 989 subjects, 107 had significant lesions, including two with GC and one with esophageal cancer. The 864 subjects who had complete morphological data taken from five gastric areas (two from the antrum and three from the corpus) comprised 419 males (mean age 48.5±7 years) and 445 females (mean age 47±6.4 years). The H. pylori rate was 76.6%. Normal mucosa was seen in 6.9%, antrum-restricted gastritis in 7.4%, antrum-predominant gastritis in 63.5% and corpus-predominant gastritis in 20% (both had >80% H. pylori infection) and corpus-restricted gastritis in 2%. More atrophy was seen in the antrum and corpus of FDR females than males. The severity did not differ between those with one or more GC patients' relatives. Forty-nine percent of FDR had atrophy and 9.4% intestinal metaplasia (IM) in the corpus. After the age of 40, there was progression of intestinal metaplasia from 12.2 to 27.3% in the antrum and from 6.7% to 26.2% in the corpus during two decades. No high grade dysplasia was found in this mid-age population. CONCLUSION: Only one-fifth of FDR have H. pylori-induced corpus-predominant gastritis who are at risk for cancer and suitable for eradication. Corpus-restricted gastritis is a rare disease in this area.

Interobserver variations in histopathological assessment of gastric pathology.

AIM: Considering the fact that histology and its grading systems are accepted gold standards in diagnosis of diverse clinical disorders, assessing the accuracy and reliability of this method of diagnosis is of utmost importance. Thus, this study was performed to measure the agreement values between four independent histopathology readings for identical indices under one scoring guideline using three different approaches. METHODS: Four independent pathologists participated in this study and were blinded to the clinical diagnosis of patients. Various histological features were examined on gastric tissue specimens according to the updated Sydney system. RESULTS: Statistical analysis revealed that our null hypothesis about the existing agreement between different histopathological observations is rejected for chronic gastritis, the presence of inflammatory activity, atrophy and Helicobacter pylori, whereas there were significant inter-observation agreements in regard to the presence of lymphoid follicles, intestinal metaplasia and dysplasia. Pairwise analysis showed that different grading scales resulted in different kappa values ranging from poor to excellent agreements. The best kappa values were observed for the evaluation of dysplasia between two independent pathologists. CONCLUSIONS: This assessment has demonstrated that standardisation of less quantitative grading scales resulting in consistent readings is essential for affirmative clinical diagnosis and devising effective treatment strategies.

P53 mutations in colorectal cancer from northern Iran: Relationships with site of tumor origin, microsatellite instability and K-ras mutations.

CRC-associated P53 mutations have not been studied extensively in non-Western countries at relatively low CRC risk. We examined, for the first time, 196 paraffin-embedded CRC cases from Northern Iran for mutations in P53 exons 5-8 using PCR-direct sequencing. P53 status and mutation site/type were correlated with nuclear protein accumulation, clinicopathologic variables and data on K-ras mutations and high-level microsatellite instability (MSI-H). We detected 96 P53 mutations in 87 (44.4%) cases and protein accumulation in 84 cases (42.8%). P53 mutations correlated directly with stage and inversely with MSI-H. Distal CRCs were more frequently mutated at major CpG hotspot codons [248 (8/66, 12.1%), 175 (7/66, 10.6%), and 245 (7/66, 10.6%)], while in proximal tumors codon 213, emerged as most frequently mutated (5/28, 17.9% vs. 3/66, 4.5%, P = 0.048). Transitions at CpGs, the most common mutation type, were more frequent in non-mucinous (25% vs. 10.4% in mucinous, P = 0.032), and distal CRC (27% vs. 12.5% in proximal, P = 0.02), and correlated with K-ras transversions. Transitions at non-CpGs, second most common P53 mutation, were more frequent in proximal tumors (15.6% vs. 4.7% in distal, P = 0.01), and correlated with K-ras transitions and MSI-H. Overall frequency and types of mutations and correlations with P53 accumulation, stage and MSI-H were as reported for non-Iranian patients. However P53 mutation site/type and correlations between P53 and K-ras mutation types differed between proximal and distal CRC. The codon 213 P53 mutation that recurred in proximal CRC was previously reported as frequent in esophageal cancer from Northern Iran.

Serum pepsinogen I, pepsinogen II, and gastrin 17 in relatives of gastric cancer patients: comparative study with type and severity of gastritis.

BACKGROUND & AIMS: First-degree relatives of gastric cancer patients are at risk for developing precancerous conditions. The aim of this study was to investigate the potential of biomarkers pepsinogen I (PGI), pepsinogen II (PGII), their ratio (PG I:II), as well as gastrin 17 for screening of precancerous conditions and corpus predominant gastritis. METHODS: First-degree relatives of gastric cancer patients underwent endoscopy. Three biopsy specimens from the antrum and 3 from the corpus were evaluated according to the Sydney classification. Serum was taken for the measurement of fasting PGI, PGII, and gastrin 17 by enzyme-linked immunosorbent assay kits. RESULTS: A total of 481 patients were examined (age, 47.8 +/- 6.7 y). With the extension of gastritis, PGII was increased up to 2.5 times (6.6 +/- 2.8 microg/mL in normal mucosa, 9.5 +/- 6.7 microg/mL in antral gastritis, and 16.9 +/- 12.4 microg/mL in corpus-predominant gastritis; P < .01), PGI increased slightly (88.3 +/- 29.4 microg/mL in normal mucosa and 111.2 +/- 71.4 microg/mL in corpus-predominant gastritis), and gastrin 17 was increased substantially in corpus-predominant gastritis (15.3 +/- 19.5 pmol/mL vs 3.8 +/- 5.7 pmol/mL in normal mucosa). By using a cut-off value of 7.5 microg/mL for PGII, any type of gastritis from normal mucosa can be diagnosed with a sensitivity and specificity of 80%. The sensitivity and specificity of the PG I:II ratio (< or =3) and gastrin 17 (>17 pmol/mL) together were 9.4% and 99% for screening corpus-predominant gastritis and 14.8% and 97.8%, respectively, for screening intestinal metaplasia in the corpus. CONCLUSIONS: PGII is a suitable marker for screening any gastritis from normal mucosa, but neither PGI, the PG I:II ratio, gastrin 17, nor their combination were able to select those with precancerous conditions and corpus-predominant gastritis among the first-degree relatives of gastric cancer patients.

Family history of colorectal cancer in Iran.

BACKGROUND: Previous reports show a high proportion of young CRC patients in Iran. In this study we aim to look for the clustering of colorectal cancer in families of a series of CRC patients from Iran. METHODS: The family history of cancer is traced in 449 CRC patients of which 112 were 45 yrs or younger and 337 were older than 45 yrs at time of diagnosis. The patients were admitted in two hospitals in Tehran, during a 4-year period. RESULTS: Clinical diagnosis of HNPCC was established in 21 (4.7%) probands. Family history of CRC was more frequently reported by early-onset than by late-onset patients (29.5% vs. 12.8%, p < 0.001). Distribution of tumor site differed significantly between those with and without family history of CRC. Right colon cancer was the most frequent site (23/45, 35.4%) observed in patients with positive family history of colorectal cancer. CONCLUSION: The relatively high frequency of CRC clustering along with HNPCC in our patients should be further confirmed with larger sample size population-based and genetic studies to establish a cost effective molecular screening for the future.

Hereditary risk factors for the development of gastric cancer in younger patients.

BACKGROUND: It is believed that the development of gastric cancer (GC) before the age of 50 has a hereditary basis. Blood group A and history of gastric cancer in first-degree relatives have been shown to be risk factors for GC. METHODS: In this case-control study, we enrolled patients with GC who were diagnosed before the age of 50. Patients who were diagnosed as having GC were selected. A total of 534 cases were found; of these, 44 diagnosed before the age of 50 were included in the case group. For the control group, 22 males and 22 females were randomly selected from the remaining subjects, who had diagnoses of GC after the age of 50. All the surviving patients and family members of the dead patients were interviewed about the history of cancer in the family and the age at which other family members developed cancer. The blood group of each subject was also obtained. RESULTS: forty-four cases under 50 years old (mean age: 36.2 years) and forty-four controls (mean age: 67.1 years) were enrolled in the study. At the time of the study, 59.1% of the study group and 50% of the control group were alive (P value = NS). In the study group, 68.1%, 13.6%, 13.6% and 4.5% had blood groups O, A, B and AB, respectively. In the control group the corresponding figures were 27.7%, 63.6%, 6.8% and 4.5%. First or second-degree relatives with cancer, including gastric (the most frequent), breast, lung, gynecological and hematological malignancies, were noted in 54.5% of the cases and 11.4% of the controls (p < 0.01). Family histories of cancer were accepted as valid provided that they were based on valid medical documents. CONCLUSIONS: It seems that the development of GC before the age of 50 is likely to be accompanied by familial susceptibility. Interestingly, our study showed a significant correlation between blood group O and the development of gastric cancer under the age of 50.