Vol 16 No 2 (2024)

Editorials

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    Gastric cancer (GC) remains a significant public health challenge in many low- and middle-income countries, particularly Iran. Despite advances in medical care and public health infrastructure, GC incidence among older adults continues to be alarmingly high. While much research has focused on adult risk factors—such as red meat consumption, smoking, alcohol intake, and Helicobacter pylori infection—emerging evidence suggests that the roots of GC extend far deeper, often tracing back to early-life conditions. Hadji M. and her colleagues published a case-control study in Iran in the current issue of Basic and Clinical Cancer Research (BCCR). They highlighted the profound influence of childhood socioeconomic factors on cancer risk decades later [1]. This study underscores the importance of adopting a life-course approach to understanding GC etiology and prevention, especially in countries like Iran. One of the most striking findings was the nearly threefold increased risk of GC associated with lack of access to clean tap water during childhood. This finding elevates sanitation from a developmental concern to a critical long-term cancer risk factor. It reflects the biological reality that early-life exposures—nutritional deprivation, microbial infections, poor housing, and inadequate hygiene—can cast a long shadow over lifelong health. Older generations in Iran experienced vastly different living conditions compared to today’s youth. Four to five decades ago, access to clean water and refrigeration was limited, particularly in rural and underserved urban areas. Children were frequently exposed to untreated water, a key transmission route for pathogens, including H. pylori [2]. Although infection rates remain high in some regions, national infrastructure improvements have dramatically increased access to electricity, clean water, and refrigeration. These changes have reduced infection rates and improved nutrition, yet the epidemiological consequences of past deprivation persist. The cohorts most affected by early-life disadvantage are now entering their 50s, 60s, and 70s—the age groups at highest risk for GC. Waiting passively for socioeconomic development to reduce GC incidence is both ethically and practically inadequate. It would mean neglecting a large population currently at elevated risk due to conditions endured decades ago: lack of sanitation, refrigeration, healthcare access, and exposure to childhood infections and malnutrition. To reduce GC incidence and mortality today, we must acknowledge these historical inequities and respond proactively. Interestingly, our study also found no significant association between GC and behaviors such as cigarette smoking, opium use, and alcohol consumption. While these are established risk factors in many contexts [3], the lack of significance here may reflect changing substance use patterns, cultural stigma leading to underreporting, or limited sample size. It also suggests that among older Iranian adults, early-life exposures and long-term dietary habits may outweigh midlife behaviors in determining GC risk.   Geographic disparities within Iran further complicate the picture. Cancer registries reveal stark variations in GC incidence—from over 20 per 100,000 in northern provinces to under five per 100,000 in southern ones [4]. These disparities closely mirror economic development and infrastructure access and will not resolve without tailored, region-specific policies. Although universal access to clean water and electricity has largely been achieved, the legacy of unequal development endures. The most immediate and cost-effective approach is targeted screening and intervention for older adults who experienced deprived childhood conditions. Outreach programs can identify individuals born in high-risk regions or those reporting limited access to sanitation, refrigeration, and clean water during childhood. These individuals may benefit from endoscopic screening, nutritional counseling, and ongoing clinical monitoring. Concurrently, education campaigns should highlight the lifelong importance of proper nutrition and hygiene, encouraging fruit and vegetable consumption, safe water use, and adequate food storage. Primary care providers should incorporate questions about early-life environmental factors—such as water source, household amenities, and parental occupation—into routine assessments to better stratify gastric cancer risk. In summary, the paper emphasizes that childhood conditions significantly influence adult cancer risk, urging a shift in prevention strategies from midlife interventions to a comprehensive life-course approach starting at birth. For countries like Iran, undergoing health transitions, addressing historical disparities, and accelerating targeted interventions is crucial to effective cancer prevention. Future research priorities include long-term cohort studies to clarify early-life exposures, geospatial mapping to link socioeconomic factors with cancer patterns, and community-based nutritional and screening interventions for high-risk groups to enhance our understanding of the etiology and improve equitable prevention of gastric cancer in Iran and other high-risk countries.

Original Articles

  • XML | PDF | downloads: 1 | views: 7 | pages: 79-85
    Background: Since its identification, the Epidermal Growth Factor Receptor (EGFR) signaling pathway through PIK3CA, has been known to be involved in the pathogenesis of several solid tumors especially Head and Neck Squamous Cell Carcinoma (HNSCC). Impaired signal transduction through EGFR-PIK3CA may give rise to oncogenic processes because of its key role in regulation of major cellular functions. Several oncogenic mechanisms mediated by unregulated EGFR signaling pathways have been suggested by previous studies including, mutations in genes encoding EGFR and PIK3CA and increased ligands of EGFR. Here, we aimed to compare the total gene expression of EGFR and PIK3CA on mRNA level between HNSCC tissues and normal squamous cell tissues. Methods:  In this pilot study, we examined 31 samples of tumor-infected squamous cell tissues as well as 31 samples of healthy tissues around the tumor as controls for the expression of EGFR and PIK3CA genes using quantitative polymerase chain reactions (Q-PCR). Results: both EGFR and PIK3CA mRNA levels were slightly altered in HNSCC tissues compared with the control group (3% decrease and 9% increase respectively) but these differences were not statistically significant. Conclusion: our results indicate that total EGRF and PIK3CA expression in mRNA level is not altered in Head and Neck Squamous Cell Carcinomas compared with that of normal squamous cell tissues.
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    Abstract Background: Cervical cancer is a multi-stage disease that is contaminated by a DNA virus and is involved in one or more stages in the pathogenesis process. In addition to human papillomaviruses (HPV), the tumor necrosis factor-α gene (TNF-α) is considered a major intermediate mediator of the acute inflammatory response to viruses and a gram-negative bacterium. The pro-region polymorphisms of the TNF-α gene such as -308 and -238 polymorphisms affect the expression of this gene. Therefore, this study aimed to investigate the polymorphisms of the TNF-α gene and its relationship with various genotypes of HPV in cervical lesions. Methods: In this study, 58 female patients with cervical cancer symptoms were selected, then following histopathologic studies, DNA was extracted from all specimens, and the PCR method was used to determine the types of HPV genotypes and TNF-α gene polymorphisms. Also, an ARMS-PCR reaction was performed to amplify TNF-α -308 and TNF-α -238 polymorphisms. Statistical analysis of the data was carried out by the Epi Info software version 7. 2 and Chi-Square (x2) test using SPSS ver.7.3.1.10. These lesions were categorized into metaplasia groups (93.37%), cervical intraepithelial neoplasia (CIN) I and II (20.68%), CIN III (15.51%) and squamous cell carcinoma (SCC) (25.86%). Results: In this study 58 lesions were collected and 26 of which were HPV positive. They were categorized as the following: 1 sample (4.53%) metaplasia, 7 samples (33.58%) CIN I and CIN II, 6 samples (66.66%) CIN III and 12 samples (80%) SCC. According to the results of statistical analysis, there was a significant difference between different types of HPV genotypes in different wastes. On the other hand, in contrast to the -238 polymorphism of the TNF-α gene, a significant difference was observed between the various types of -308 polymorphism of the TNF-α gene in the three groups of metaplasia, CIN, and SCC. In general, we can conclude that GG genotype testing of the -308 polymorphism of TNF-α gene and HPV types in combination with para-clinical parameters can be effective as risk factors and molecular markers for prognosis and early treatment of cervical cancer.    
  • XML | PDF | downloads: 1 | views: 6 | pages: 98-110
    Background: We conducted a historical cohort study and studied the survival rate and prognostic factors of oral cavity squamous cell carcinoma among patients admitted at the Cancer Institute of Iran. Methods: We recruited 352 patients who were referred to the Cancer Institute hospital in 2004-2011. Patients were newly diagnosed and pathologically confirmed as oral cavity squamous cell carcinoma. We abstracted data from the archived medical records and followed up with the patients until their death or end of follow-up in January 2015. Results: A total number of 347 patients (212 males and 135 females) were analyzed in this study. Surgery, alone or in combination with other modalities, was performed in 308 (88.8%) patients. The median time of follow-up was 18.7 months. The 1, 3, and 5-year survival were 84%, 53%, and 41%, respectively. The risk of death was significantly higher in patients older than 70 years of age (HR: 2.0, 95% CI: 1.1-3.7), moderately differentiated tumors (HR: 3.6, 95% CI: 1.3-9.7), “surgery with adjuvant treatment” group (HR: 2.6, 95% CI: 1.6-4.2), and the “surgery with neoadjuvant treatment” group (HR: 3.1, 95% CI: 1.4-7.0). Patients diagnosed with a higher TNM staging also experienced a higher probability of death. An increase in the number of involved lymph nodes was another independent indicator of outcome. Conclusion: the 5-year survival rate of oral cancer was 41% among patients admitted to the Cancer Institute of Iran. A higher survival rate in early-stage oral cancer patients indicates the importance of early detection among these patients.
  • XML | PDF | downloads: 3 | views: 8 | pages: 111-118
    Background: - Her-2neu is a gene from the epidermal growth factor receptor family. It is known to regulate cell growth. Her-2neu overexpression or amplification is more common in type2 endometrial cancer than in type1. Overexpression of Her-2neu has been associated with poor prognosis. This study aims to evaluate Her-2neu expression in endometrial carcinoma patients. Method: - 50 endometrial carcinoma patients were enrolled in the study. Her-2neu expression was studied by immunohistochemistry method on formalin fixed paraffin embedded tissue and correlated with clinical and pathological parameters as well as disease status. Result: - Her-2neu positivity was observed in 10% (5/50) of cases. Her-2neu expression was more frequent in postmenopausal women (10%). Her-2neu expression was more common in patientslymphovascular invasion (18%) and lymph node positivity (20%). A higher frequency of Her-2neu expression was seen in ER negative (22%), p53 mutant type (17%), WT1 positive (25%) and Vimentin positive (12%) tumors. In relation to disease free survival, Her-2neu positive tumors had a higher rate of relapse. Conclusion: - In the present study, higher expression of Her-2neu was observed in patients with lymphovascular invasion, lymph node positivity, ER negative, p53 mutant tumors, WT1 positive, Vimentin positive patients and those with reduce DFS (Disease Free Survival). The above findings suggest that Her-2neu to be associated with disease spread, its aggressiveness, proliferation in hormone-independent manner, its role in EMT (Epithelial-Mesenchymal Transition) process and negative prognostic implications.    
  • XML | PDF | downloads: 3 | views: 6 | pages: 119-130
    Lung cancer represents a significant public health challenge, representing a considerable contributor to cancer-related mortality. However, the current diagnostic methods for early detection of lung cancer are constrained by various limitations, such as inadequate clinical resources and effective screening modalities. Consequently, diagnosis frequently occurs at advanced stages, impeding timely treatment interventions. However, the emerging field of omics, including metabolomics, proteomics, and genomics, has shown some improvement in facilitating the early diagnosis of lung cancer. Metabolomics methodologies offer a comprehensive insight into the metabolic processes of cells and tissues, enabling a deeper understanding of the biological state. By analyzing endogenous metabolites within biological systems, metabolomics has exhibited substantial potential for early detection and personalized treatment of diverse cancers. In this study, we extensively explored online metabolomic databases, such as Metabolomics Workbench, to pinpoint key metabolites linked to all types of lung cancer. Furthermore, connections between metabolomic genes and 43 genes implicated in lung cancer progression have been established by employing network analysis tools like Metagenes. This integrated approach offers a comprehensive overview of the metabolic and molecular landscape of lung cancer, highlighting 10 metabolic pathways, particularly amino acid metabolism, involved in the pathogenesis of lung cancer. These findings provide valuable insights for further research and potential clinical applications in the diagnosis and management of this disease.