Combining mammaglobin and carcinoembryonic mRNA markers for early detection of micrometastases from breast cancers - a molecular study of 59 patients

Introduction: As many as 30% of node-negative breast cancer patients relapse within five years, suggesting that current histological detection methods are inadequate for identifying metastatic disease. Detecting small number of cancer cells in the breast tissue or lymph node by reverse transcription-polymerase chain reaction (RT-PCR) assays using a combination of tissue and cancer specific markers might be very useful in the early detection or monitoring of the treatment. Mammaglobin is a member of the uteroglobin gene family and appears to be expressed only in breast tissue. Carcinoembryonic antigen has been the preferred molecular marker for detection of micro metastases in lymph nodes in almost all carcinomas. Materials and Methods: Samples were collected from randomly chosen breast cancer patients undergoing modified mastectomy or breast conserving surgery between September 2003 and July 2004. RT-PCR was applied to study the expression of MMG and CEA markers. Breast cancer micrometastases in axillary lymph nodes were also assessed. Results: The MMG marker was positive in 9/10 normal breast tissues, 3/ 3 breast fibroadenomas and 37/39 of breast carcinoma tissues, giving an overall sensitivity of 94%. The sensitivity was 80% for metastatic lymph node samples. On the other hand CEA showed 95% sensitivity for malignant breast tumors and 100% sensitivity for metastatic lymph nodes. Conclusions: RT-PCR using a combination of MMG and CEA markers is a powerful tool to complement current routine histopathology techniques for detection of breast cancer metastasis in axillary nodes

Relationship between urbanization and cancer incidence in Iran using quantile regression

Quantile regression is an efficient method for predicting and estimating the relationship between explanatory variables and percentile points of the response distribution, particularly for extreme percentiles of the distribution. To study the relationship between urbanization and cancer morbidity, we here applied quantile regression. This cross-sectional study was conducted for 9 cancers in 345 cities in 2007 in Iran. Data were obtained from the Ministry of Health and Medical Education and the relationship between urbanization and cancer morbidity was investigated using quantile regression and least square regression. Fitting models were compared using AIC criteria. R (3.0.1) software and the Quantreg package were used for statistical analysis. With the quantile regression model all percentiles for breast, colorectal, prostate, lung and pancreas cancers demonstrated increasing incidence rate with urbanization. The maximum increase for breast cancer was in the 90th percentile (β=0.13, p-value < 0.001), for colorectal cancer was in the 75th percentile (β=0.048, p-value < 0.001), for prostate cancer the 95th percentile (β=0.55, p-value < 0.001), for lung cancer was in 95th percentile (β=0.52, p-value=0.006), for pancreas cancer was in 10th percentile (β=0.011, p-value < 0.001). For gastric, esophageal and skin cancers, with increasing urbanization, the incidence rate was decreased. The maximum decrease for gastric cancer was in the 90th percentile(β=0.003, p-value < 0.001), for esophageal cancer the 95th (β=0.04, p-value=0.4) and for skin cancer also the 95th (β=0.145, p-value=0.071). The AIC showed that for upper percentiles, the fitting of quantile regression was better than least square regression. According to the results of this study, the significant impact of urbanization on cancer morbidity requirs more effort and planning by policymakers and administrators in order to reduce risk factors such as pollution in urban areas and ensure proper nutrition recommendations are made. © 2016, Asian Pacific Journal of Cancer Prevention

Systematic review of available guidelines on fertility preservation of young patients with breast cancer

Background: Since the survival rate of breast cancer patients has improved, harmful effects of new treatment modalities on fertility of the young breast cancer patients has become a focus of attention. This study aimed to systematically review and critically appraise all available guidelines for fertility preservation in young breast cancer patients. Materials and Methods: Major citation databases were searched for treatment guidelines. Experts from relevant disciplines appraised the available guidelines. The AGREE II Instrument that includes 23 criteria in seven domains (scope and purpose of the guidelines, stakeholder involvement, rigor of development, clarity, applicability, editorial independence, and overall quality) was used to apprise and score the guidelines. Results: The search strategy retrieved 2,606 citations; 72 were considered for full-text screening and seven guidelines were included in the study. There was variability in the scores assigned to different domains among the guidelines. ASCO (2013), with an overall score of 68.0, had the highest score, and St Gallen, with an overall score of 24.7, had the lowest scores among the guidelines. Conclusions: With the promising survival rate among breast cancer patients, more attention should be given to include specific fertility preservation recommendations for young breast cancer patients

Estimating the incidence of lung cancer attributable to occupational exposure in Iran

<p>Abstract</p> <p>Objective</p> <p>The aim of this study was to estimate the fraction of lung cancer incidence in Iran attributed to occupational exposures to the well-established lung cancer carcinogens, including silica, cadmium, nickel, arsenic, chromium, diesel fumes, beryllium, and asbestos.</p> <p>Methods</p> <p>Nationwide exposure to each of the mentioned carcinogens was estimated using workforce data from the Iranian population census of 1995, available from the International Labor Organization (ILO) website. The prevalence of exposure to carcinogens in each industry was estimated using exposure data from the CAREX (CARcinogen EXposure) database, an international occupational carcinogen information system kept and maintained by the European Union. The magnitude of the relative risk of lung cancer for each carcinogen was estimated from local and international literature. Using the Levin modified population attributable risk (incidence) fraction, lung cancer incidence (as estimated by the Tehran Population-Based Cancer Registry) attributable to workplace exposure to carcinogens was estimated.</p> <p>Results</p> <p>The total workforce in Iran according to the 1995 census identified 12,488,020 men and 677,469 women. Agriculture is the largest sector with 25% of the male and 0.27% of female workforce. After applying the CAREX exposure estimate to each sector, the proportion exposed to lung carcinogens was 0.08% for male workers and 0.02% for female workers. Estimating a relative risk of 1.9 (95% CI of 1.7–2.1) for high exposure and 1.3 (95% CI 1.2–1.4) for low exposure, and employing the Levin modified formula, the fraction of lung cancer attributed to carcinogens in the workplace was 1.5% (95% CI of 1.2–1.9) for females and 12% (95% CI of 10–15) for males. These fractions correspond to an estimated incidence of 1.3 and 0.08 cases of lung cancer per 100,000 population for males and females, respectively.</p> <p>Conclusion</p> <p>The incidence of lung cancer due to occupational exposure is low in Iran and, as in other countries, more lung cancer is due to occupational exposure among males than females.</p

Mutation analysis of BRCA1 and BRCA2 genes in Iranian high risk breast cancer families

Background: Telomerase is a ribonucleoprotein enzyme that synthesises telomeres after cell division and maintains chromosomal stability leading to cellular immortalization. Telomerase has been associated with negative prognostic indicators in some studies. The present study aims to detect any association between telomerase sub-units: hTERT and hTR and the prognostic indicators including tumour's size and grade, nodal status and patient's age. Methods: Tumour samples from 46 patients with primary invasive breast cancer and 3 patients with benign tumours were collected. RT-PCR analysis was used for the detection of hTR, hTERT, and PGM1 (as a housekeeping) genes expression. Results: The expression of hTR and hTERT was found in 31(67.4%) and 38 (82.6%) samples respectively. We observed a significant association between hTR gene expression and younger age at diagnosis (p = 0.019) when comparing patients ≤ 40 years with those who are older than 40 years. None of the benign tumours expressed hTR gene. However, the expression of hTERT gene was revealed in 2 samples. No significant association between hTR and hTERT expression and tumour's grade, stage and nodal status was seen. Conclusion: The expression of hTR and hTERT seems to be independent of tumour's stage. hTR expression probably plays a greater role in mammary tumourogenesis in younger women (≤ 40 years) and this may have therapeutic implications in the context of hTR targeting strategies

Qualitative analysis of Adenomatous Polyposis Coli promoter: Hypermethylation, engagement and effects on survival of patients with esophageal cancer in a high risk region of the world, a potential molecular marker

<p>Abstract</p> <p>Background</p> <p>Squamous cell carcinoma of esophagus (SCCE) occurs at a high incidence rate in certain parts of the world. This feature necessitates that different aspects of the disease and in particular genetic characteristics be investigated in such regions. In addition, such investigations might lead to achievement of molecular markers helpful for early detection, successful treatment and follow up of the disease. Adenomatous Polyposis Coli (<it>APC</it>) promoter hypermethylation has been shown to be a suitable marker for both serum and solid tumors of adenocarcinoma of esophagus. We investigated the status of <it>APC </it>promoter hypermethylation in Iranian patients, compared the results with the former studies, and evaluated its applicability as a candidate molecular marker by examining association between survival of SCCE patients and <it>APC </it>promoter methylation.</p> <p>Methods</p> <p>For evaluating the status of <it>APC </it>promoter hypermethylation and its association with SCCE, a qualitative methylation specific PCR (MSP) was used. DNA was extracted and digested with an appropriate restriction enzyme, treated with sodium bisulfite in agarose beads and amplified in two-step PCR reaction by applying either methylated or unmethylated promoter specific primers. Universally methylated DNA and methylase treated blood DNA of healthy donors were used as positive controls as well. Survival of patients was followed up for two years after treatment and survival rate of patients with methylated <it>APC </it>promoter was compared with that of unmethylated patients.</p> <p>Results</p> <p>Assessment of <it>APC </it>promoter methylation revealed that normal tissues were unmethylated, while twenty out of forty five (44.4%) tumor tissues were hypermethylated either in one or both alleles of <it>APC</it>. Among the tissues in which methylation was detected, seven were hypermethylated in both alleles while the other thirteen were hypermethylated in one of the two alleles of <it>APC</it>. Analyzing two-year survival rate of patients with respect to promoter hypermethylation showed a lower rate of survival for patients with methylated <it>APC </it>promoter following their treatment. Further investigation into the association between promoter hypermethylation and tumor differentiation status indicated that patients with well differentiated tumors were more likely to develop promoter hypermethylation.</p> <p>Conclusion</p> <p>Observing similar level of <it>APC </it>promoter hypermethylation in patients with SCCE in this high risk region and comparing it with other parts of the world could support the hypothesis that a common molecular mechanism might be involved in tumorigenesis of SCCE. In addition, the higher rate of two-year survival for patients with unmethylated <it>APC </it>promoter as well as its relationship with tumor differentiation would suggest that this tumor suppressor could be an appropriate candidate molecular marker for evaluating tumor malignancy and predicting survival of patients subsequent to treatment.</p

Effects of gene polymorphisms of metabolic enzymes on the association between red and processed meat consumption and the development of colon cancer; a literature review

The role of environmental factors and genetic susceptibility in the development of colon cancer (CC) has been already proven, but the role of gene polymorphisms in modifying the risk of environmental factors such as nutritional factors is still unknown. This study aimed to investigate the effect of polymorphisms of involved genes in the association between red meat consumption and the development of CC. The present review was carried out using keywords such as polymorphism and/or protein and/or red meat and/or processed meat and/or colon cancer. PubMed and Science Direct databases were used to collect all related articles published from 2001 to 2017. The presence of SNP in the coding genes of proteins involved in metabolism of nutrients could play significant roles in the extent of the effects of nutrition in the development of CC. The effect of dietary proteins greatly depends on the polymorphisms in the metabolising genes of these substances. Gene polymorphisms may have a role in colorectal cancer risk, especially in people with high meat intake, and this leads to a difference in the effects of meat consumption in different individuals. To conclude, dietary recommendations for the prevention and control of CC should be modified based on the genotype of different individuals. Increasing our knowledge on this field of nutritional genomics can lead to personalised preventive and therapeutic recommendations for CC patients

Polymorphisms in Genes Coding for Folate-Related Enzymes and Colorectal Cancer

This review examined the association between folate and risk of colorectal cancer and single-nucleotide polymorphisms in 4 genes coding for folate metabolism-related enzymes may be involved. Individuals with single-nucleotide polymorphisms in these key enzymes in the folate pathways may need different amounts of dietary folate to prevent colorectal cancer

Serum vitamin D level may be associated with body weight and body composition in male adolescents � a longitudinal study

Introduction: The prevalence of both obesity and vitamin D deficiency has been dramatically increased worldwide. Aim of the study: This study aimed to investigate the association between vitamin D serum level and anthropometric indices of overweight and obese male adolescents at baseline and after 18 weeks of a weight reduction intervention. Methods: This study was carried out on 90 male students aged 12 to 16 years who were randomly selected from two schools in Tehran, Iran. The participants were assigned to two groups with high and low vitamin D level based on their serum vitamin D levels at baseline. Five ml blood samples were collected at the baseline and after the 18 weeks of a weight reduction intervention. Height, weight, body mass index (BMI), body fat percent and body muscle percent were measured using a bio impedance analysis (BIA) scale. Results: Vitamin D level in non-obese adolescents was significantly higher than the obese participants (44.01 vs 37.67 ng/dl, p < 0.04). However, there was no significant correlation between changes of vitamin D level and anthropometric measurements after 18 weeks. Adjusting the effect of age did not alter the association. Further adjustments for physical activity, dietary intake of vitamin D, and fat and muscle percentage had no effect on the results. Conclusion: The serum level of vitamin D was negatively associated with obesity, but not with short-term changes of anthropometric measurements in male adolescents. © Copyright by PTEiDD 2020