• Asian Pacific Journal of Cancer Prevention
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• 제17권2호
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• pp.603-608
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• 2016

Background: The investigation of mutation patterns in oncogenes potentially can make available a reliable mechanism for management and treatment decisions for patients with colorectal cancer (CRC). This study concerns the rate of KRAS and BRAF genes mutations in Iranian metastatic colorectal cancer (mCRC) patients, as well as associations of genotypes with clinicopathological features. Materials and Methods: A total of 1,000 mCRC specimens collected from 2008 to 2012 that referred to the Mehr Hospital and Partolab center, Tehran, Iran enrolled in this cross sectional study. Using HRM, Dxs Therascreen and Pyrosequencing methods, we analyzed the mutational status of KRAS and BRAF genes in these. Results: KRAS mutations were present in 33.6% cases (n=336). Of KRAS mutation positive cases, 85.1% were in codon 12 and 14.9% were in codon 13. The most frequent mutation at KRAS codon 12 was Gly12Asp; BRAF mutations were not found in any mCRC patients (n=242). In addition, we observed a strong correlation of KRAS mutations with some clinicopathological characteristics. Conclusions: KRAS mutations are frequent in mCRCs while presence of BRAF mutations in these patients is rare. Moreover, associations of KRAS genotypes with non-mucinous adenocarcinoma and depth of invasion (pT3) were remarkable.

• Asian Pacific Journal of Cancer Prevention
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• 제15권22호
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• pp.9773-9779
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• 2014

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 $56.5{\pm}9.59$ 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.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7621-7628
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• 2013

Human epidermal growth factor receptor (HER) status is an important prognostic factor in breast cancer. There is no globally accepted method for determining its status, and which method is most precise is still a matter of debate. We here analyzed HER2 mRNA expression by quantitative reverse transcription-PCR (qRT-PCR) and HER2 DNA amplification using multiplex ligation-dependent probe amplification (MLPA). In parallel, we performed a routine evaluation of HER2 protein by immunohistochemistry (IHC). To assess the accuracy of the RT-PCR and MLPA techniques, a combination of IHC and fluorescence in situ hybridization (FISH) was used, substituting FISH when the results of IHC were ambiguous (2+) and for those IHC results that disagreed with MLPA and qRT-PCR, this approach being termed IHC-FISH. The IHC results for four samples were not compatible with the MLPA and qRT-PCR results; the MLPA and qRT-PCR results for these samples were confirmed by FISH. The correlations between IHC-FISH and qRT-PCR or MLPA were 0.945 and 0.973, respectively. The ASCO/CAP guideline IHC/FISH correlation with MLPA was (0.827) and with RT-PCR was (0.854). The correlations between the IHC results (0, 1+ as negative, and 3+ as positive) and qRT-PCR and MLPA techniques were 0.743 and 0.831, respectively. Given the shortcomings of IHC analysis and greater correlations between MLPA, qRT-PCR, and FISH methods than IHC analysis alone with each of these three methods, we propose that MLPA and real-time PCR are good alternatives to IHC. However a suitable cut-off point for qRTPCR is a prerequisite for determining the exact status of HER2.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7651-7656
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• 2013

Background: Breast cancer is the most common malignancy among women in both developed and developing countries. The burden is increasing in low-income and middle-income countries (LMCs) and threatens the public health of such societies. Introduction of expensive monoclonal antibodies to cancer treatment regimens poses a real challenge in the health systems of LMCs. Despite controversy of cost-effectiveness of bevacizumab in breast cancer, some studies indicate gain of patients from this drug. The present study aimed to propose a priority setting model for administration of anti-angiogenic agents in breast cancer via assessment of tumor angiogenesis by the microvessel density (MVD) method and associations with clinicopathological characteristics (including simultaneous mutations of TP53 and HER-2 genes). Materials and Methods: Age, axillary lymph nodes status, tumor size, stage and grade, estrogen and progesterone receptors status, HER-2/neu status (by immunohistochemistry and FISH test), TP53 mutation, Ki-67 (for proliferation assay) and CD34 (for angiogenesis assay) were assessed in 111 breast cancer patients. The molecular subtype of each tumor was also determined and correlations of simultaneous mutations of HER-2 and p53 genes with angiogenesis and other clinicopathological characteristics were evaluated. Results: There were significant associations between simultaneous mutations of HER-2 and p53 genes and all other parameters except tumor size. The degree of angiogenesis in the ERBB2 subtype was greater than the others. Younger patients showed a higher angiogenesis rate rather those older than 50 years. Conclusions: Our results demonstrated that patients with simultaneous mutations of HER-2 and p53 genes, those with ERBB2 molecular subtype and also younger women (often triple negative) seem more eligible for obtaining anti-angiogenic agents. These results suggest a model for priority setting of patients with breast cancer for treatment with anti-angiogenic drugs in LMCs.

• Journal of Gastric Cancer
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• 제14권3호
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• pp.196-203
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• 2014

Purpose: Vascular endothelial growth factor (VEGF) is one of the most important growth factors for metastatic tumors. To clarify the role of VEGF-A and C in patients with peptic ulcer disease (PUD) or gastric cancer (GC), we evaluated the expression levels of these two molecules. We also analyzed the effect of Helicobacter pylori infection on VEGF-A and C expression levels. Materials and Methods: Patients with dyspepsia who needed diagnostic endoscopy were selected and divided into three groups: nonulcer dyspepsia (NUD), PUD, and GC, according to their endoscopic and histopathological results. Fifty-two patients with NUD, 50 with PUD, and 38 with GC were enrolled in this study. H. pylori infection was diagnosed by the rapid urease test. After RNA extraction and synthesis of cDNA, the expression levels of VEGF-A and C were determined by quantitative reverse transcriptase polymerase chain reaction. Results: The VEGF-C expression level in the PUD and GC groups was significantly higher than that in the NUD group. Moreover, the VEGF-A expression level in the PUD and GC groups was higher than in the NUD group, although the differences were not statistically significant. Significant positive correlations were also observed between the expression levels of these two molecules in the PUD and GC groups. In addition, the expression levels of these two molecules were higher in H. pylori positive patients with PUD or GC than in H. pylori negative patients of the same groups; however, these differences did not reach statistical significance. Conclusions: Up-regulation of VEGF-C expression during gastric mucosal inflammation may play a role in the development of peptic ulcers or GC.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1407-1412
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• 2012

Background & Objectives: Gastric cancer is a leading cause of cancer-related deaths in both sexes in Iran. This study was designed to assess upper GI endoscopic findings among people > 50 years targeted in a mass screening program in a hot-point region. Methods: Based on the pilot results in Guilan Cancer Registry study (GCRS), one of the high point regions for GC-Lashtenesha- was selected. The target population was called mainly using two methods: in rural regions, by house-house direct referral and in urban areas using public media. Upper GI endoscopy was performed by trained endoscopists. All participants underwent biopsies for rapid urea test (RUT) from the antrum and also further biopsies from five defined points of stomach for detection of precancerous lesions. In cases of visible gross lesions, more diagnostic biopsies were taken and submitted for histopathologic evaluation. Results: Of 1,394 initial participants, finally 1,382 persons (702 women, 680 men) with a mean age of $61.7{\pm}9.0$ years (range: 50-87 years) underwent upper GI endoscopy. H. pylori infection based on the RUT was positive in 66.6%. Gastric adenocarcinoma and squamous cell carcinoma of esophagus were detected in seven (0.5%) and one (0.07%) persons, respectively. A remarkable proportion of studied participants were found to have esophageal hiatal hernia (38.4%). Asymptomatic gastric masses found in 1.1% (15) of cases which were mostly located in antrum (33.3%), cardia (20.0%) and prepyloric area (20.0%). Gastric and duodenal ulcers were found in 5.9% (82) and 6.9% (96) of the screened population. Conclusion: Upper endoscopy screening is an effective technique for early detection of GC especially in high risk populations. Further studies are required to evaluate cost effectiveness, cost benefit and mortality and morbidity of this method among high and moderate risk population before recommending this method for the GC surveillance program at the national level.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6905-6911
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• 2013

Background: Breast cancer (BC) is the top cancer among women worldwide and the most frequent malignancy among Iranian women over the past few decades. The increasing trend and high mortality rate of BC in the developing world necessitates studies concentrating on its characteristics in countries in Asia. The current study focused on clinical and histopathological features of BC among Iranian females. Materials and Methods: This retrospective study involved 714 Iranian patients with histopathologically proven BC undergoing resection of primary tumours and axillary clearance. Demographic, clinical and histopathological data were obtained and studied between ten year age groups (${\leq}40$ years, 41-50 years, 51-60 years, 61-70 years, and ${\leq}71$ years) in four chronologic phases from 1994-2009. Results: Mean age of patients was $49.4{\pm}13.1$ years. Most of cases (33.2%) were in 41-50 group. Mean size of primary tumors was $3.94{\pm}2.47$ cm and 87.1% of cases had infiltrative ductal carcinoma. Modified radical mastectomy was the most common method of surgery carried out (48.8%). Some 57.1% of tumors were in pT2 and tumor size decreased significantly during the period (p<0.05). The most common BC stage was llla (27%). Lower BC stages (0 and 1) constituted 13.9% of the diagnosed tumors. Our series of patients aged ${\leq}40$ had larger tumors (mean $4.73{\pm}3.02$ cm) compared to older age groups (p=0.003). Lower stages (0 and I) were more frequent among the oldest patients while nearly 50% of patients aged ${\leq}40$ had tumor stage III. We also observed a significant decreasing trend in the mean LN count (p<0.05) and blood vessel invasion (p=0.023) from younger to older age groups. Conclusions: More aggressive disease for younger age groups, earlier peak incidence age and high rate of advanced BC at the time of diagnosis among Iranian women, were the main findings of this study.

• Asian Pacific Journal of Cancer Prevention
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• 제17권1호
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• pp.419-424
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• 2016

Background: The aim of this systematic review was to study the relationship between exposure to nitrogen dioxide ($NO_2$) in the ambient air and breast cancer incidence. Materials and Methods: A systematic review was performed based on the MOOSE guideline for review of observational studies. We searched five online databases (PubMed, Science Direct, Google Scholar, EBSCO, and Scopus) from their conception to June 2014. A pooled estimate of the correlation between $NO_2$ exposure and breast cancer incidence was calculated using Pearson's correlation coefficient. Results: A total of 654 titles were retrieved in the initial search of the databases. Further refinement and screening of the retrieved studies produced a total of five studies from four countries. The studies included three ecological studies (aggregate level) and two individual based studies (one prospective cohort and the other one a case-control study). The ecological studies were pooled and the meta-analysis of correlation coefficient without z transformation showed a pooled estimate of r = 0.89 with 95% CI of 0.84 to 0.95. Using z transformation, the pooled r was 1.38 with 95%CI of 1.11 to 1.59. No significant heterogeneity between studies was observed. Following a sensitivity analysis and the removal of each study from pooled analysis we did not see any significant change in the pooled estimate. Conclusions: It was concluded that there is a tendency toward a weak association between exposure to $NO_2$ in ambient air and breast cancer at the individual level and a significant association at the aggregate level.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6171-6176
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• 2014

Background: In order to design effective educational intervention for cancer survivors, it is necessary to identify most-trusted sources for health-related information and the amount of attention paid to each source. Objective: The objective of our study was to explore the sources of health information used by cancer survivors according to their access to the internet and levels of trust in and attention to those information sources. Materials and Methods: We analyzed sources of health information among cancer survivors using selected questions adapted from the 2012 Health Information National Trends Survey (HINTS). Results: Of 357 participants, 239 (67%) had internet access (online survivors) while 118 (33%) did not (offline survivors). Online survivors were younger (p<0.001), more educated (p<0.001), more non-Hispanic whites (p<0.001), had higher income (p<0.001), had more populated households (p<0.001) and better quality of life (p<0.001) compared to offline survivors. Prevalence of some disabilities was higher among offline survivors including serious difficulties with walking or climbing stairs (p<0.001), being blind or having severe visual impairment (p=0.001), problems with making decisions (p<0.001), doing errands alone (p=0.001) and dressing or bathing (p=0.001). After adjusting for socio-demographic status, cancer survivors who were non-Hispanic whites (OR= 3.49, p<0.01), younger (OR=4.10, p<0.01), more educated (OR= 2.29, p=0.02), with greater income (OR=4.43, p<0.01), and with very good to excellent quality of life (OR=2.60, p=0.01) had higher probability of having access to the internet, while those living in Midwest were less likely to have access (OR= 0.177, p<0.01). Doctors (95.5%) were the most and radio (27.8%) was the least trusted health related information source among all cancer survivors. Online survivors trusted internet much more compared to those without access (p<0.001) while offline cancer survivors trusted health-related information from religious groups and radio more than those with internet access (p<0.001 and p=0.008). Cancer survivors paid the most attention to health information on newsletters (63.8%) and internet (60.2%) and the least to radio (19.6%). More online survivors paid attention to internet than those without access (68.5% vs 39.1%, p<0.001) while more offline survivors paid attention to radio compared to those with access (26.8% vs 16.5%, p=0.03). Conclusions: Our findings emphasize the importance of improving the access and empowering the different sources of information. Considering that the internet and web technologies are continuing to develop, more attention should be paid to improve access to the internet, provide guidance and maintain the quality of accredited health information websites. Those without internet access should continue to receive health-related information via their most trusted sources.

• Asian Pacific Journal of Cancer Prevention
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• 제17권sup3호
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• pp.275-278
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• 2016

The membrane epithelial mucin MUC1 is expressed at the luminal surface of most simple epithelial cells, but expression is greatly increased in most breast cancers. The aims of present study were to investigate expression of the MUC1 gene and interactive affects in metastases. Whole cell RNA isolation from 50 sentinel lymph nodes (SNLs) of breast cancer patients was performed using reverse transcription and real-time PCR. All patients were diagnosed with breast cancer and without metastasis, confirmed by IHC staining. The evaluation of tumor and normal samples for expression of MUC1 gene, the results were 49.1% non-expressive and 45.3% expression (Student t, p = 0.03). Also in comparison of normal breast tissue and breast cancer SLN for MUC1 gene, MUC1 negative SLNs were 75.0% (18 samples) and MUC1 positive samples were 25.0% (6 samples). Over-expression of MUC1 gene may offer a target for therapy related to progression and metastasis in women with breast cancer.