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Breast cancer is the most frequent cancer with second mortality rate in women worldwide. Lack of validated biomarkers for early detection of breast cancer to warranty the diagnosis and effective treatments in early stages has directed to the new therapeutic approach. Cancer/testis antigens which have restricted normal expression in testis and aberrant expression in different cancers are promising targets for generating cancer vaccines, monoclonal antibodies, or dendritic cell-based immunotherapy. In this context, we investigated the expression of two known cancer testis genes, Aurora kinase C (AURKC) and testis expressed 101 (TEX101), and one new candidate, deleted in azoospermia 1 (DAZ1), in six breast cancer cell lines including two ductal carcinomas, T47D and BT-474, and four adenocarcinomas, MDA-MB-231, MDA-MB-468, MCF7, and SKBR3 as well as 50 breast cancer tumors in comparison to normal mammary epithelial cells using quantitative real-time reverse transcription PCR (RT-PCR). Results showed significant overexpression (p = 0.000) of all three genes in BT474, DAZ1 in MDA-MB-231, and AURKC and DAZ1 in SKBR3 and significant downregulation (p = 0.000) of AURKC in MCF7 cell line relative to normal breast epithelial cells. Breast tumors showed significant overexpression of AURKC in comparison to normal breast tissues (p = 0.016). The results are noticeable especially in the case of AURKC; however, there is a little knowledge about the nature, causes, consequences, and effects of cancer/testis antigens activation in different cancers. It is suggested that AURKC has effects on cell division via its serin/threonin kinases activity and organizing microtubules in relation to centrosome/spindle function during mitosis.

Aim: Gestational trophoblastic neoplasm (GTN) is a rare disease which is classified into high- and low-risk groups. While the high-risk patients require combination therapy, the low-risk groups respond to single-agent chemotherapy. We studied resistance to single-agent chemotherapy and its risk factors among the low-risk GTN patients in Iran., Methods: We followed 168 low-risk GTN patients who were treated between 2001 and 2011 in Valiasr Hospital, Tehran, Iran. We used a case-control design and studied odds ratios (OR) and corresponding 95% confidence intervals (CI) to evaluate association between drug resistance and different personal and clinical variables., Results: Resistance to sequential single-agent chemotherapy was 19%, although all patients had a complete remission after a combination of chemotherapy and/or surgery. Patients who had International Federation of Gynecology and Obstetrics scores of 5-6 - considered as, the intermediate risk group - had a 14-fold higher resistance compared with the low score patients (OR = 14.28, 95% CI = 5.54-36.81). We found higher risk of resistance among patients with metastasis (OR = 8.42, 95% CI = 2.44-29.07), large tumor size (>3 cm) (OR = 7.73, 95% CI = 1.93-30.91), high β-hCG (>100 000 IU/L) (OR = 5.86, 95% CI = 1.07-32.02) and/or a diagnosis more than 4 months after pregnancy (OR = 3.30, 95% CI = 1.08-10.02), compared with their reference group. We found no priority for the different chemotherapy regimens., Conclusion: Intermediate risk GTN patients had a higher risk of resistance to chemotherapy compared with low-risk patients. Clinical trials and cost-effectiveness studies are needed to suggest a better treatment program for the intermediate risk group., (© 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.)

The prognostic role of matrix metalloproteinase-7 in gastric cancer survival has been widely evaluated. However, the results are controversial. We aimed to set up a meta-analysis to reach a conclusion on the prognostic significance of metalloproteinase-7 in gastric cancer survival as well as its association with clinicopathological parameters. We searched popular databases from 1988 until October 2014 to gather eligible peer-reviewed papers addressing the prognostic effect of matrix metalloproteinase-7 in gastric cancer patients' survival. The CASP check list was used for quality appraisal. Pooled hazard ratio (HR) for survival and odds ratio (OR) for association with their 95% confidence interval (CI) were considered as summary measurements. Finally, 1208 gastric cancer patients from nine studies were included in the meta-analysis. Pooled HR estimate for survival was 2.01 (95% CI = 1.62 - 2.50, P < 0.001), which indicated a significant poor prognostic effect for matrix metalloproteinase-7. Sensitivity analysis detected no dominancy for any study. No publication bias was detected according to Egger's and Begg's tests. Clinicopathological assessment revealed that higher matrix metalloproteinase-7 expression is associated with deeper invasion (pooled OR = 3.20; 95% CI = 1.14 - 8.96; P = 0.026), higher TNM stage (pooled OR = 3.67; 95% CI = 2.281-5.99; P<0.001), lymph node metastasis (pooled OR = 2.84; 95% CI = 1.89 - 4.25; P<0.001), and distant metastasis (pooled OR = 3.68; 95% CI = 1.85 - 7.29; P<0.001), but not with histological grade. This meta-analysis indicated a significant poor prognostic effect of matrix metalloproteinase-7 in gastric cancer survival. Additionally it was associated with aggressive tumor phenotype.

Background: The incidence and mortality rates of cancer are increasing worldwide, particularly in the developing countries. Valid data are needed for measuring the cancer burden and making appropriate decisions toward cancer control. We evaluated the completeness of death registry with regard to cancer death in Fars Province, I. R. of Iran., Methods: We used data from three sources in Fars Province, including the national death registry (source 1), the follow-up data from the pathology-based cancer registry (source 2) and hospital based records (source 3) during 2004 - 2006. We used the capture-recapture method and estimated underestimation and the true age standardized mortality rate (ASMR) for cancer. We used log-linear (LL) modeling for statistical analysis., Results: We observed 1941, 480, and 355 cancer deaths in sources 1, 2 and 3, respectively. After data linkage, we estimated that mortality registry had about 40% underestimation for cancer death. After adjustment for this underestimation rate, the ASMR of cancer in the Fars Province for all cancer types increased from 44.8 per 100,000 (95% CI: 42.8 - 46.7) to 76.3 per 100,000 (95% CI: 73.3 - 78.9), accounting for 3309 (95% CI: 3151 - 3293) cancer deaths annually., Conclusion: The mortality rate of cancer is considerably higher than the rates reported by the routine registry in Iran. Improvement in the validity and completeness of the mortality registry is needed to estimate the true mortality rate caused by cancer in Iran.

To evaluate the effect of adding neoadjuvant chemotherapy to surgery and radiation therapy for locally advanced resectable oral cavity squamous cell carcinoma, 24 patients with T3 or T4a oral cavity squamous cell carcinoma were randomly assigned to surgery alone or Docetaxel, Cisplatin, and 5-FU (TPF) induction chemotherapy followed by surgery. All patients were planned to receive chemoradiotherapy after surgery. The primary end-points were organ preservation and progression-free-survival. SPSS version 17 was used for data analysis. Median follow-up was 16 months. The median age of the patients was 62 years old (23-75 years). Man/woman ratio was 1.13. The primary site of the tumor was the tongue in most patients (48%). No significant difference was observed between pathologic characteristics of the two groups. Chemotherapy group showed 16% complete pathologic response to TPF. No significant difference in organ preservation surgery or overall survival was detected. However, the patients in the chemotherapy group had longer progression-free-survival (P=0.014). Surgery followed by chemoradiotherapy with or without TPF induction results in similar survival time. However, progression-free-survival improves with the TPF induction chemotherapy. Studies with more patents and new strategies are recommended to evaluate organ preservation improvement and long-term outcomes.

Objectives: Fumonisins are a group of toxic and carcinogenic mycotoxins, which contaminate the grains and their products. The aim of this study was to examine the apoptotic and proliferative activity of mouse gastric mucosa following administration of fumonisin B1 (FB1)., Materials and Methods: Twenty-nine female mice divided into treatment (n=15) and control (n=14) groups. The treatment group received FB1 (150 mg/kg diet) for 16 weeks. The gastric atrophy was allocated using grading criteria modeled on the updated Sydney System. Immunohistochemistry studies were performed for evaluation of apoptosis and proliferative activity in gastric mucosa., Results: Mild to moderate gastric atrophy were observed in microscopic findings of the gastric mucosa in treated animals (P<0.05). Number of parietal cells significantly decreased in the treatment group in comparison with the control (P<0.05). Treatment with FB1 for 16 weeks significantly reduced both gastric mucosa height and mitotic index in the gastric glands (P<0.05). TUNEL- and Bax-labeled positive cell numbers significantly increased in the FB1-treated group compared to the control (P<0.05). In addition, proliferative activity of gastric glands in the treated group was significantly lower than the control (P<0.05)., Conclusion: Oral administration of FB1 caused atrophy in gastric mucosa both via increasing of apoptosis and suppressing the mitotic activity of these cells.

Background: Fundamental etiologic differences have been suggested to cause earlier onset of breast cancer in less developed countries (LDCs) than in more developed countries (MDCs). We explored this hypothesis using world-wide breast cancer incidence data., Methods: We compared international age-standardized incidence rates (ASR) of pre- (<50 years) and postmenopausal (≥50 years) breast cancers as well as temporal trends in ASRs of pre-and postmenopausal breast cancer among selected countries during 1975-2008. We used joinpoint log-linear regression analysis to estimate annual percent changes (APC) for premenopausal and postmenopausal breast cancer in the northern Europe and in Black and White women population in the US., Results: Premenopausal breast cancers comprised a substantially higher proportion of all incident breast cancers in LDCs (average 47.3%) compared to MDCs (average 18.5%). However, the ASR of premenopausal breast cancer was consistently higher in MDCs (29.4/100,000) than LDCs (12.8/100,000). The ASR of postmenopausal cancer was about five-fold higher in the MDCs (307.6/100,000) than the LDCs (65.4/100,000). The APC of breast cancer in Denmark was substantially higher in postmenopausal (1.33%) than premenopausal cancer (0.98%). Higher incidence of breast cancer among the white than black women in the US was pertained only to the postmenopausal cancer., Conclusion: The substantial and consistent lower age-specific incidence of breast cancer in LDCs than in MDCs contradicts the theory of earlier onset. Demographic differences with fewer old women in LDCs and lower prevalence of risk factors of postmenopausal cancer are the most likely explanation to the lower mean age at diagnosis in these countries.

Background: Breast cancer is the most common cancer among women. Mammography screening has been used in many countries to reduce early deaths caused by breast cancer. It is important to ensure that screening programs are effective and efficient. We conducted a study to assess the cost-effectiveness of a national breast cancer screening program implemented in Iran., Methods: The perspective of the present study was the health system. Over 26,000 women aged 35 and higher, of low socioeconomic background were recruited from ten cities in the program. We used case-finding as the outcome indicator for assessing effectiveness of the program. We measured the service provision costs, the coordination costs and supervision costs of the program that included the staff costs, and measured cost per detected case. We also conducted sensitivity analyses and calculated false-positive rates as a result of the screening program., Results: The total cost of breast cancer screening program was estimated at $377,797. The program resulted in the identification of 24 patients with breast cancers, not different from baseline expectations without a screening program. The cost per cancer detected was calculated $15,742. The minimum and maximum cost per breast cancer detected were about $13,524 and $16,947, respectively. We observed a false-positive rate of 7.5% among the target population., Conclusion: Our findings suggest that the mammography screening program was not cost-effective. Although there were technical efficiency issues in the conduct of the program, the findings do not support the implementation of national mammography screening programs in Iran in women aged less than 50 years. Careful studies of such programs for higher age groups are also recommended before they are rolled-out nationally.

Background: Oral cancer is the most common malignant tumor among head and neck cancers. Delay in diagnosis affects the treatment and prognosis of oral cancer. We measured the professional delay in the diagnosis and its attributes in the Cancer Institute of Iran, the largest referral center for oral cancer patients in the country. , Methods: We interviewed oral cancer patients to measure the delay and used case-control approach to study association of various prognostic factors with professional delay and tumor stage., Result: Out of 206 patients, 71.4% were diagnosed at the advanced stage. The median of the patient, professional and total delays were 45, 86 and 140 day, receptively. In the univariate model, prescription of medicines like analgesics (OR = 5.3, 95% CI 2.2-12.9) and history of dental procedure (OR=6.8, 95% CI 1.7-26.9) were associated with higher risk of delay compared to patient who were biopsied from the beginning. History of loose teeth increased risk of delay 4 times (OR = 4.0, 95% CI 1.6-9.8). Patients with primary education had 70% lower risk of delay compared to the illiterate patients (OR = 0.3, 95% CI 0.1-0.7) and the risk was lower among patients who had diploma (OR = 0.04, 95% CI 0-0.7) and college education (OR = 0.1, 95% CI 0-0.4). The delayed patients were diagnosed in more advanced stage compared to the patients without delay (OR = 2.1, 95% CI 1.0-4.4)., Conclusion: Development of a national guideline for follow-up of oral lesions, training and awareness of health care professionals about oral cancer diagnosis may decrease the delay and improve the oral cancer outcome in Iran.

Introduction: Iran was engaged in the Program of Action for Cancer Therapy (PACT) in 2012, and delegates from the International Atomic Energy Agency (IAEA), and the World Health Organization (WHO) evaluated the National Cancer Control Program (NCCP) status (the imPACT mission), based on which they provided recommendations for improvements of NCCP in the I.R. of Iran. We reported the results of this situational analysis and discussed the recommendations and their implication in the promotion of NCCP in the I.R. of Iran. , Methods: International delegates visited the I.R. of Iran and evaluated different aspects and capacities of NCCP in Iran. In addition, a Farsi version of the WHO/IAEA self-assessment tool was completed by local experts and stakeholders, including experts from different departments of the Ministry of Health and Medical Education (MOHME) and representatives from the National Cancer Research Network (NCRN). Following these evaluations, the PACT office provided recommendations for improving the NCCP in Iran. Almost all the recommendations were endorsed by MOHME., Results: The PACT program provided 31 recommendations for improvement of NCCP in Iran in six categories, including planning, cancer registration and information, prevention, early detection, diagnosis and treatment, and palliative care. The most important recommendation was to establish a strong, multi-sectoral NCCP committee and develop an updated national cancer control program., Conclusion: The imPACT mission report provided a comprehensive view about the NCCP status in Iran. An appropriate response to these recommendations and filing the observed gaps will improve the NCCP status in the I.R. of Iran.

Purpose: Uncertainty is a major component in the illness experiences which extraordinarily can affect the psychological adjustment and the illness outcomes. Uncertainty in illness is defined as inability to define the illness-related events to the illness or disability in predicting the illness outcomes. The present study aimed to translate the Persian version of Uncertainty in Illness Scale (MUIS-A) and to investigate its psychometric properties on patients with cancer., Method: In this methodological study, validation of the Persian version of MUIS-A was performed in Iran on 420 cancer patients attending two major hospitals in Tehran, Iran. The scale was translated into Persian and back translated into English and revised according to editorial comments of the scale designers. Then, content and face validity, construct validity, internal consistency reliability and stability of the Persian version were measured. Data were analyzed using SPSS version 16 and LISREL 8.5., Results: Mean of the participants MUIS-A score was 90.1 (16.8). Confirmatory factor analysis confirmed validity of the whole instrument and its four subscales. The consistency of the instrument with a three-week interval was r = 0.91. Cronbach's alpha was 0.89 for the whole scale of 32 MUIS-A items and α = 0.58-0.86 for its four factors., Conclusions: The Persian version of the MUIS-A has good psychometric properties. It can be used to assess uncertainty in illness in Iranian patients with cancer., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Cervical cancer is a common, preventable and manageable disease in women worldwide., Objectives: This study was conducted to determine the cost of follow-up for suspicious precancerous cervical lesions within a screening program using Pap smear or HPV DNA test through the decision tree., Materials and Methods: Patient follow-up processes were determined using standard guidelines and consultation with specialists to design a decision tree model. Costs of treatment in both public and private sectors were identified according to the national tariffs in 2010 and determined based on decision tree and provided services (visits to specialists, colposcopy, and conization) with two modalities: Pap smear and HPV DNA test. The number of patients and the mean cost of treatment in each sector were calculated. The prevalence of lesions and HPV were obtained from literature to estimate the cost of treatment for each woman in the population., Results: Follow-up costs were determined using seven processes for Pap smear and 11 processes for HPV DNA test. The total cost of using Pap smear and HPV DNA process for each woman in the population was 36.1$ and 174 $ respectively., Conclusions: The follow-up process for patients with suspicious cervical lesions needs to be included in the existing screening program. HPV DNA test is currently more expensive than Pap smear, it is suggested that we manage precancerous cervical lesions with this latter test.

Background: In vitro, in vivo and clinical studies have demonstrated anti-cancer effects of deuterium depleted water (DDW). The nature of this agents action, cytotoxic or cytostatic, remains to be elucidated. We here aimed to address the point by examining effects on different cell lines., Materials and Methods: 3-(4, 5-dimethylthiazol- 2-yl)-2, 5-diphenyltetrazolium bromide (MTT) -based cytotoxicity analysis was conducted for human breast, stomach, colon, prostate cancer and glioblastoma multiforme cell lines as well as human dermal fibroblasts. The cell lines were treated with decreasing deuterium concentrations of DDW alone, paclitaxel alone and both. One way analysis of variance (ANOVA) was used for statistical analysis., Results: Treatment with different deuterium concentrations of DDW alone did not impose any significant inhibitory effects on growth of cell lines. Paclitaxel significantly decreased the survival fractions of all cell lines. DDW augmented paclitaxel inhibitory effects on breast, prostate, stomach cancer and glioblastoma cell lines, with influence being more pronounced in breast and prostate cases., Conclusions: DDW per se does not appear to have inhibitory effects on the assessed tumor cell lines as well as normal fibroblasts. As an adjuvant, however, DDW augmented inhibitory effects of paclitaxel and thus it could be considered as an adjuvant to conventional anticancer agents in future trials.

Background: Organized cervical screening has decreased the incidence of cervical cancer. However, screening strategies vary in different countries., Objectives: We performed a systematic review to evaluate the economic aspects of different screening methods., Materials and Methods: We searched databases and then data were abstracted from each study. We evaluated articles based on different types of screening tests as well as screening age and intervals, and using incremental cost effectiveness ratio via calculating quality adjusted life years (QALY), or life years gained (LYG) per cost. We compared the incremental cost-effectiveness ratio (ICER) of each study using GDP per capita. Furthermore, we compared national guidelines with recommendations of cost- effectiveness studies in different countries., Results: A total of 21 articles met our criteria, of which 19 studies showed that HPV DNA testing, 13 suggested an age of 30 years or more, and 10 papers concluded that at least a 5-year or longer interval were the most cost-effective strategies. In some countries, the national guidelines did not match the recommendations of the cost-effectiveness studies., Conclusions: HPV testing, starting at age 30 years or older and repeated at 5-year or longer intervals, is the most cost-effective strategy in any setting. Closer collaboration with health economists is required during guideline development.

Background: The activator protein-1 (AP-1) transcription factor is believed to be important in tumorigenesis and altered AP-1 activity was associated with cell transformation. We aimed to assess the potential role of AP-1 family members as novel biomarkers in breast cancer., Methods: We studied the expression of AP-1 members at the mRNA level in 72 primary breast tumors and 37 adjacent non-tumor tissues and evaluated its correlation with clinicopathological parameters including estrogen receptor (ER), progesterone receptor (PR) and HER2/neu status. Expression levels of Ubiquitin C (UBC) were used for normalization. Protein expression of AP-1 members was assessed using Western blot analysis in a subset of tumors. We used student's t-test, one-way ANOVA, logistic regression and Pearson's correlation coefficient for statistical analyses., Results: We found significant differences in the expression of AP-1 family members between tumor and adjacent non-tumor tissues for all AP-1 family members except Fos B. Fra-1, Fra-2, Jun-B and Jun-D mRNA levels were significantly higher in tumors compared to adjacent non-tumor tissues (p < 0.001), whilst c-Fos and c-Jun mRNA levels were significantly lower in tumors compared with adjacent non-tumor tissues (p < 0.001). In addition, Jun-B overexpression had outstanding discrimination ability to differentiate tumor tissues from adjacent non-tumor tissues as determined by ROC curve analysis. Moreover, Fra-1 was significantly overexpressed in the tumors biochemically classified as ERα negative (p = 0.012) and PR negative (p = 0.037). Interestingly, Fra-1 expression was significantly higher in triple-negative tumors compared with luminal carcinomas (p = 0.01)., Conclusions: Expression levels of Fra-1 and Jun-B might be possible biomarkers for prognosis of breast cancer.

Objectives: Medical students, as tomorrow's doctors, are responsible for their patients' health; cheating may affect their academic knowledge and clinical skills. The main purpose of this study was to investigate the frequency of and attitudes towards academic disintegrity among medical students at Tehran University of Medical Sciences (TUMS)., Methods: Anonymous questionnaires including questions about various types of academic disintegrity were distributed among medical students during the clerkship and internship phases of the curriculum. Randomised response technique (RRT) was used to maintain the responders' privacy. Because the study design guaranteed the confidentiality of respondents, the TUMS Institutional Review Board declared that formal ethical approval was not required., Results: A total of 124 students were enrolled in this study, of whom 63 were in the clerkship phase and 61 were in the internship phase. Of these respondents, 29% (n = 36) were male. The most frequently reported type of academic disintegrity was found to be 'impersonating an absent student in a class' (93%) and the least frequent to be 'legitimising absences by using bribes' (5%). Only a small number of interns considered 'buying hospital shifts', 'selling hospital shifts', 'impersonating an absent student' and 'helping others to cheat in examinations' as representing academic disintegrity. Approximately one third of participants stated that the RRT increased their confidence in anonymity and 90% of students found the use of RRT not difficult., Conclusions: Academic integrity is widely disrespected in different ways among medical students. Effective policies and interventions are required to control these misbehaviours in future doctors in order to optimise medical practice. Almost all respondents found it not difficult to use the RRT; the technique proved to be an effective and easily applied method of eliciting truthful responses to sensitive questions and represents an alternative to conventional anonymising techniques., (© Blackwell Publishing Ltd 2013.)

Background: Few studies have evaluated the epidemiology of cervical cancer in low risk Muslim countries, where the prognosis of cervical cancer is poor and which lack an organized cervical screening program. We studied incidence and mortality rates of cervical cancer and the prevalence of high risk human papilloma virus (HPV) infection in the Islamic Republic (I.R.) of Iran., Methods: We analyzed national cancer and mortality registration data and estimated age-standardized incidence (ASR) and mortality (ASMR) rates and age-specific patterns of cervical cancer. Furthermore, based on a systematic review we estimated prevalence of HPV infection in Iran., Results: The mean cervical cancer ASR was 2.5 per 100,000 in pathology-based cancer registries. However, ASRs were almost double in the population-based cancer registry and reached 6 per 100,000. The mean cervical cancer ASMR for Iran was 1.04 per 100,000. The mortality to incidence ratio was 42%. The cervical cancer incidence rate increased after age 30 and peaked between ages 55 and 65. The prevalence of HPV infection was 76% in cervical cancer patients and 7% among healthy Iranian women. Of the HPV types isolated, HPV 16 (54%), 18 (14%), and 31 (6%) were the most commonly detected in Iranian cervical cancer patients., Conclusions: An organized prevention program is needed to fight against cervical cancer in Iran and other low incidence countries. We suggest a screening program starting after age 30 and with at least three screenings tests over each woman's lifetime. With a reservation on cost-effectiveness issue, available HPV vaccine will prevent HPV infection and cervical cancer in Iran., (Copyright © 2012 Elsevier Inc. All rights reserved.)

In December 2011, the Cancer Research Centre of the Cancer Institute of Iran sponsored a 3-day workshop on "Cancer Registration Principle and Challenges in Iran", which convened cancer registry experts. The objectives of the workshop were: to introduce standard cancer registration, to review the policy and procedure of cancer registration in Iran, and to review the best practices in the cancer registries in Iran. Challenges to cancer registration were discussed and recommendations were developed. The workshop was evaluated by participants for better organization of subsequent workshops. The objective of publication of this report is that based on Cancer in 5 Continents, many low- or middle-income countries do not meet the criteria for a standard population-based cancer registry (PBCR); on the other hand cancer is the most important cause of mortality and the essential part of any cancer control program is the cancer registry. Therefore this report focuses on problems and challenges of PBCR and provides recommendations which might help other developing countries to decrease their PBCR defects.

Background: Mouse mammary tumor virus (MMTV) is the major cause of mammary tumors in mice. There is limited controversial evidence about the probable etiologic role of MMTV- like virus in human breast cancer., Materials and Methods: A total of 40 Formalin fixed paraffin embedded samples with diagnosis of breast cancer were collected in a period of 3 years from cancer institute of Iran. We selected both pre-menopausal and post-menopausal patients with different histologic grades and different ethnic groups. We evaluated presence of MMTV-like virus env gene through real time PCR method., Results: Forty patients (20 pre and 20 post- menopausal women) were evaluated with the mean age of 49.67. The average tumor size was 39 mm. None of the studied samples were positive for MMTV-like virus env gene target sequences., Conclusions: We found no evidence on the potential role of MMTV-like virus in the carcinogenicity of breast cancer among Iranian women.

Introduction: Little data is available on the prognosis of esophageal cancer (EC) in Iran. We studied the short- and long-term survival of EC patients treated at the Cancer Institute of Iran., Methods: 619 patients were followed who had been operated in the years 1997-2006. The 1-month to 5-year survival rates of EC and hazard ratios (HR) for different prognostic factors were estimated., Results: Median survival was 11.5 months and 5-year survival was 10%. Patients at the advanced stage had a 2.1-fold higher risk of mortality compared to the early stage (95% CI 1.2-3.4). One-month mortality decreased from 12.2 in 1997-1999 to 9.1% in 2003-2006. In the first month, patients who were diagnosed in 2003-2006 had a significantly (60%) lower HR compared to 1997-1999 (HR = 0.4, 95% CI 0.1-0.9). In addition, patients with cardiopulmonary complications had an 11.7-fold higher HR compared to patients without complications (95% CI 4.7-29.3)., Conclusions: The 5-year survival rate for operated EC patients was considerably low in Iran. Cardiopulmonary complications were the strong prognostic factors for first-month mortality. We suggest improving the pre- and postoperative care of EC to control these complications. Regular monitoring of patient survival is recommended to evaluate the effect of this intervention., (Copyright © 2013 S. Karger AG, Basel.)

Background: Stomach cancer is the most common cancer in Iran. A multi-ethnic population and wide variation in the environmental risk factors may lead to variations in cancer risk within this country. We have designed an ecological study and evaluated geographical variation regarding mortality from stomach cancer and its established risk factors in Iran. , Methods: We used the Iranian National Causes of Death Registry and estimated the age-standardized mortality rates (ASMR) of stomach cancer in 29 Iranian provinces, stratified by sex and area of residence (rural/urban). , Results: The average ASMR of stomach cancer among Iranian males was 15 per 100,000 and for females it was 8.1 per 100,000. The highest and lowest mortality rates were observed in Kurdistan with an ASMR of 29.1 per 100,000 in northwestern Iran and Hormozgan that had an ASMR of 5.0 per 100,000 in southern Iran. Males had approximately a two-fold higher ASMR compared to females, as did rural residents when compared with urban residents. The prevalence of H. pylori infection was about 90% in the province of Ardabil (a high-risk area) and 27% in the province of Sistan-Baluchistan (a low-risk area). , Conclusions: The wide geographical variation and high mortality rate of stomach cancer in Iran is likely due to differences in the exposure to the environmental risk factors among people living in the high- and low-risk areas, particularly H. pylori infection, a well-established risk factor of stomach cancer.

Cervical cancer is one of the most common cancers among women worldwide, although cervical screening has reduced the incidence in many high-income countries. Low screening uptake among immigrant women may reflect differences in risk of cervical cancer. We investigated the degree of participation in cervical screening among immigrant and Swedish-born women and their concurrent risk of cervical cancer based on individual information on Pap smears taken both from organized and opportunistic screening. Mean degree of participation in cervical screening was estimated for women between 23 and 60 years from 1993 to 2005, stratified by birth region and age at migration. In Poisson regression models, we estimated relative risks (RRs), incidence rates and incidence rate ratios of cervical cancer for women adhering or not to the cervical screening program. We also assessed effect of adherence to screening on the risk of cervical cancer among immigrant groups compared to Swedish-born women. The degree of participation was 62% and 49% among Swedish-born and immigrant women, respectively, with large variations between immigrant groups. Participation was lowest among those immigrating at older ages. Swedish-born and immigrant women who where nonadherent to the cervical screening program had a fivefold excess risk of cervical cancer compared to adherent women. After adjustment for screening adherence, excess RRs of cervical cancer were statistically significant only for women from Norway and the Baltic States. Participation to screening is lower among immigrant than Swedish-born women, and adherence to the recommended screening intervals strongly prevents cervical cancer., (Copyright © 2011 UICC.)

The mitochondrial DNA (mtDNA) mutations in mitochondrial coding and non coding regions seem to be important in carcinogenesis. The aim of this investigation was to evaluate coding region (mt-tRNA(Phe) and tRNA(Pro)) and non-coding sequence, mitochondrial displacement loop (mtDNA D-loop), in the cancerous and non-cancerous lesions of Iranian patients with breast cancer (BC). Genomic DNA was extracted from 50 breast tumors and surrounding normal tissue pairs as well as from 50 unrelated normal breast tissues from Iranian Kurdish population. Subsequently, PCR amplification was performed using specific primers, and then PCR products were subjected to direct sequencing. 41 genetic variants were identified in mtDNA D-loop among tumoral and non-tumoral tissues but not in tRNA(Phe) and tRNA(Pro) sequences. Our findings indicated that C182T, 194insT, 285insA and 16342delT were just found in BC tumors whereas 302insC, C309T and C16069T found in both tumors and surrounding normal tissues. Although our findings showed that the observed genetic variations were not restricted to breast cancer tissues, some genetic changes were found only in BC tumors. Our results, in agreement with the evidence from earlier studies, confirm that the mtDNA genetic alterations might be implicated in tumor initiation, progression and development.

Objectives: Achalasia is a motor disorder of the lower esophageal sphincter, which fails to relax on swallowing. Although a greater risk of esophageal squamous cell carcinoma among achalasia patients is fairly well established, no epidemiological study has evaluated the risk of esophageal adenocarcinoma in these patients., Methods: We compiled a cohort of 2,896 patients recorded with a discharge diagnosis of achalasia between 1965 and 2003 in the Swedish Inpatient Register. The cohort was followed through 2003 via record linkages with essentially complete registers of cancer, causes of death, and migration. Standardized incidence ratios (SIRs) were used to estimate the relative risk of esophageal cancer in achalasia patients compared to the age-, sex-, and calendar period-matched Swedish population. We further estimated SIRs for esophageal cancer among patients treated with esophagomyotomy., Results: After excluding the first year of follow-up, we observed excess risks for both squamous cell carcinoma (SIR 11.0, 95% confidence interval [CI] 6.0-18.4) and adenocarcinoma (SIR 10.4, 95% CI 3.8-22.6) of the esophagus. Notwithstanding similar numbers of men and women in our achalasia cohort, 20 of 22 esophageal cancers developed in men (SIRs for adenocarcinoma and squamous cell carcinoma were 8.4 and 13.1, respectively). Increased SIRs among operated patients pertained mainly to esophageal squamous cell carcinoma. We found no evidence that surgical esophagomyotomy increases the risk of esophageal adenocarcinoma., Conclusions: Male achalasia patients have substantially greater risks for both squamous cell carcinoma and adenocarcinoma of the esophagus. Small numbers preclude a firm conclusion about the risk among women.

Background: Stomach cancer is the most common cancer among Iranian men. We studied survival rates and prognostic factors of stomach cancer in a referral hospital in Tehran, Iran., Patients and Methods: We followed 367 stomach cancer patients hospitalized between 1991 and 2007 in the Baqyiatallah Hospital. We estimated survival rates overall and among operable patients exclusively. Hazard ratios (HR) for the different prognostic factors were estimated with the Cox regression model. Furthermore, we studied international variations in stage distribution and 5 year survival for stomach cancer., Results: Overall, 5 year survival of stomach cancer was low (14%), and the majority of patients (53%) were diagnosed at stage IV. Stage, tumor size, age, and gender were statistically significant prognostic factors. Relative risk of mortality in stage IV compared to stage IA was 9.9 (95% confidence interval 5.8-16.9). The highest 5 year survival was reported from Japan, particularly among screening detected patients (89.4%). Among operable patients, 5 year survival was 32.6% in France, 26% in the USA, and 30.5% in China, which was close to the rates estimated in our study (24%)., Conclusions: Due to stomach cancer being frequently diagnosed in advanced stages, its prognosis is poor in Iran. Early diagnosis and downstaging strategies need to be prioritized to improve the prognosis of stomach cancer., (Copyright © 2011 S. Karger AG, Basel.)

Objectives: In this pilot randomized clinical trial the preventive effects of weekly granulocyte colony stimulating factor (GCSF) injection for patients with central nervous system (CNS) tumors receiving craniospinal irradiation were assessed with regard to risk of treatment interruption., Methods: We randomized 40 CNS cancer patients into two groups (20 patients each), the first receiving GCSF prevention therapy before weekly craniospinal radiotherapy and the control group without this prophylaxis. The main outcome was whether GCSF preventive therapy decreased the rate of interruption of radiotherapy because of leucopenia and thrombocytopenia. We used t -test, and chi-square test statistics to compare the quantitative and qualitative outcomes., Results: there were no significant differences in platelets and WBC loss between the treatment and control groups. Treatment interruption was lower in weekly GCSF therapy group (35%), compared to the control group (55%), although the difference was not statistically significant (P value 0.2). While 8 patients (40%) also received GCSF therapy due to leucopenia in the control group only one patient reached a critical level and needed GCSF therapy because of irradiation complications (p-value 0.02). Among those who received naodjuvant chemotherapy (8 patients in each group), among the GCSF prevention group only in one (12%) we had to interrupt radiotherapy, as compared to 6 in the control group due to WBC loss., Conclusion: Weekly GSCF injections among CNS tumor patients receiving craniospinal therapy may decrease treatment interruption. A larger study with longer follow-up is now needed to confirm our results.

Glutathione S-transferase (GST) enzymes are known to metabolize tobacco-related carcinogens. Previous studies on the association of functional polymorphisms of GST genes with esophageal squamous cell carcinoma have yielded conflicting but overall null results. A few studies of esophageal adenocarcinoma were likewise conflicting, but the scarcity of data is striking. We aimed to study associations of the GSTM1 and GSTT1 null deletion polymorphisms as well as the GSTP1 Ile105Val polymorphism with risks for esophageal and gastric cardia cancers. DNA was prepared from 96 and 79 cases of esophageal adenocarcinoma and squamous cell carcinoma, respectively, 126 cardia cancer cases, and 471 population-based controls. Pyrosequencing typed the GSTP1 Ile105Val polymorphism, while multiplex PCR detected GSTM1 and GSTT1 deletions. Logistic regression modeling estimated odds ratios (ORs) with 95% confidence intervals (CIs). None of the studied polymorphisms were related to the risk of esophageal adenocarcinoma, but the variant GSTP1 Val(105) allele was associated with an increased risk of esophageal squamous cell carcinoma (OR = 1.7; 95% CI 1.0-2.9) and tended to be weakly, positively linked to cardia cancer (OR = 1.4; 95% CI 0.9-2.1). Finally, we performed a meta-analysis and found that GSTP1 polymorphism seems to be associated with the risk of esophageal squamous cell carcinoma among Caucasian population (OR = 1.4; 95% CI 1.0-2.2; p value for heterogeneity test 0.34).

Unlabelled: Sulfur mustard (SM), also known as mustard gas, is an alkylating compound used as a chemical weapon in World War I and by Iraqi forces against Iranians and indigenous Iraqi Kurds during the Iran-Iraq War of the 1980s. Although SM is a proven carcinogen there are conflicting views regarding the carcinogenicity of a single exposure. The present study characterizes lung cancers formed in mustard gas victims from the Iran-Iraq War., Methods and Materials: Demographic information and tumor specimens were collected from 20 Iranian male lung cancer patients with single high-dose SM exposures during the Iran-Iraq War. Formalin-fixed, paraffin-embedded lung cancers were analyzed by immunohistochemistry for p53 protein. In addition, DNA was extracted from the tissues, PCR amplified and sequenced to identify mutations in the p53 and KRAS genes associated with SM exposure., Results: A relatively early age of lung cancer onset (ranging from 28 to 73 with a mean of 48) in mustard gas victims, particularly those in the non-smoking population (mean age of 40.7), may be an indication of a unique etiology for these cancers. Seven of the 20 patients developed lung cancer before the age of 40. Five of 16 cancers from which DNA sequence data was obtainable provided information on eight p53 mutations (within exons 5-8). These mutations were predominately G to A transitions; a mutation consistent with the DNA lesion caused by SM. Two of the lung cancers had multiple p53 point mutations, similar to results obtained from factory workers chronically exposed to mustard agent. No mutations were detected in the KRAS gene., Discussion: The distinguishing characteristics of lung carcinogenesis in these mustard gas victims suggest that a single exposure may increase the risk of lung cancer development in some individuals.

Because of great variation in the prevalence of human papilloma virus infection and other risk factors of cervical cancer worldwide, migrant studies may help further the understanding of the aetiology and improve prevention of cervical cancer. Our aim was to study the risk of invasive cervical cancer among immigrant women. We followed 758,002 immigrants from different countries who resided in Sweden between 1968 and 2004. Age-standardised incidence rates (ASRs) of immigrants were compared with that in their countries of origin. Poisson regression models estimated the relative risks of cervical cancer among immigrants, overall and stratified by age at migration and follow-up time, compared to Swedish-born women. Overall 1,991 of 19,542 observed cases of cervical cancer occurred among immigrants. Generally they had lower ASRs than in their countries of origin, with the exception of Nordic immigrants. Compared to Swedish-born women, we observed a higher relative risk of cervical cancer among immigrants overall (RR = 1.13, 95% CI 1.08-1.18), and particularly among women from Denmark (RR = 1.8, 95% CI 1.6-2.1), Norway (RR = 1.7, 95% CI 1.5-1.9) and Central America (RR = 2.5, 95% CI 1.3-4.9), while the relative risks were lower in immigrants from Eastern Africa (RR = 0.2, 95% CI 0.1-0.6), South Central Asia (RR = 0.4, 95% CI 0.2-0.6) and South Western Asia (RR = 0.5, 95% CI 0.4-0.7). Follow-up time and age at migration were important effect modifiers for cervical cancer risks. We suggest targeted prevention toward high-risk immigrants, specifically older women, in the first 10 years after arrival into their new homeland., ((c) 2008 Wiley-Liss, Inc.)

Although Scandinavian moist snuff ("snus"), no doubt, is a safer alternative to smoking, there is limited evidence against an association with gastroesophageal cancers. In a retrospective cohort study, we investigated esophageal and stomach cancer incidence among 336,381 male Swedish construction workers who provided information on tobacco smoking and snus habits within a health surveillance program between 1971 and 1993. Essentially complete follow-up through 2004 was accomplished through linkage to several nationwide registers. Multivariable Cox proportional hazards regression models estimated relative risks (RR) and 95% confidence intervals (CIs). Compared to never-users of any tobacco, smokers had increased risks for adenocarcinoma (RR = 2.3, 95% CI 1.4-3.7) and squamous cell carcinoma (RR = 5.2, 95% CI 3.1-8.6) of the esophagus, as well as cardia (RR = 2.1, 95% CI 1.5-3.0) and noncardia stomach (RR = 1.3, 95% CI 1.2-1.6) cancers. We also observed excess risks for esophageal squamous cell carcinoma (RR = 3.5, 95% CI 1.6-7.6) and noncardia stomach cancer (RR = 1.4, 95% CI 1.1-1.9) among snus users who had never smoked. Although confounding by unmeasured exposures, and some differential misclassification of smoking, might have inflated the associations, our study provides suggestive evidence for an independent carcinogenic effect of snus., ((c) 2007 Wiley-Liss, Inc.)

In a prospective cohort study of more than 330,000 Swedish construction workers, we explored the effect of tobacco smoking, oral moist snuff use, and body mass index (BMI) on the risk of developing leukemia (excluding chronic lymphocytic leukemia) and multiple myeloma (MM). Study subjects were participants of a health surveillance system within the building industry. Record linkage to the nationwide Swedish cancer registry, migration registry, and cause of death registry made a comprehensive follow-up available. A total of 372 incident cases of leukemia and 520 subjects with MM was ascertained. An increase in risk of acute myelogenous leukemia (AML) was observed in current smokers (incidence rate ratio, 1.50; 95% confidence interval, 1.06-2.11). Furthermore, there was an indication of a possible association between smoking intensity and risk of acute lymphocytic leukemia. Results on snuff use as well as BMI showed no association. This study confirms the role of smoking as a risk factor for AML and gives no support to the hypothesis of a role of snuff use or BMI level on the risk of leukemia or MM.

Although patients with type 2 diabetes have elevated risks of liver, pancreatic, kidney, and endometrial cancer, little is known about the risk of cancer for patients with type 1 diabetes. We conducted a cohort study to examine cancer incidence among 29 187 patients in Sweden who were hospitalized for type 1 diabetes from 1965 through 1999. Relative risks of cancer were estimated by age-, sex- and calendar year of follow-up--adjusted standardized incidence ratios (SIRs), using data for the entire Swedish population as a reference. After excluding cancers diagnosed during the first year after hospital discharge, we observed 355 incident cases of cancer, which corresponded to a 20% increase in overall cancer incidence among type 1 diabetes patients (SIR = 1.2, 95% confidence interval [CI] = 1.0 to 1.3). Patients with type 1 diabetes had elevated risks of cancers of the stomach (SIR = 2.3, 95% CI = 1.1 to 4.1), cervix (SIR = 1.6, 95% CI = 1.1 to 2.2), and endometrium (SIR = 2.7, 95% CI = 1.4 to 4.7). Type 1 diabetes is associated with a modest excess cancer risk overall and risks of specific cancers that differ from those associated with type 2 diabetes.

Objective: To evaluate the effects of fasting on anthropometric indices and carbohydrate and lipid metabolism in patients with type II diabetes., Design: Observational non-interventional study., Place and Duration of Study: : Diabetes clinic, Shariati Hospital, Tehran, Iran during Ramadan 1419 (winter 1998-99)., Patients and Methods: Fifty-seven volunteers with type II diabetes underwent anthropometric and biochemical evaluation before and on the 14th and 28th days of Ramadan. Biochemical markers were measured by standard laboratory methods and anthropometric indices by WHO criteria. Statistical analysis was done by ANOVA for repeated measurements and Friedman's two-way ANOVA using SPSSv6 software., Results: Daily cholesterol intake increased in all subjects (p<0.03). Body mass index increased in women (p<0.03), but BMI and waist-hip ratio both decreased in men (p<0.01). Blood pressure, fasting blood glucose and serum fructosamine did not change during the study. Plasma insulin (p<0.05), C-peptide (p<0.01) and insulin resistance (p<0.01) decreased only in men. Total and LDL cholesterol increased significantly in all subjects during the study., Conclusion: Ramadan fasting does not alter carbohydrate metabolism or tissue insulin sensitivity in patients with type II diabetes given appropriate dietary education and rescheduling of oral hypoglycaemic medication. Lipid profile is unfavourably altered due to changes in both diet and biochemical response to starvation.