Exploring the geospatial epidemiology of breast cancer in Iran: identifying significant risk factors and spatial patterns for evidence-based prevention strategies.

BACKGROUND: Breast Cancer (BC) is a formidable global health challenge, and Iran is no exception, with BC accounting for a significant proportion of women's malignancies. To gain deeper insights into the epidemiological characteristics of BC in Iran, this study employs advanced geospatial techniques and feature selection methods to identify significant risk factors and spatial patterns associated with BC incidence. METHODS: Using rigorous statistical methods, geospatial data from Iran, including cancer-related, sociodemographic, healthcare infrastructure, environmental, and air quality data at the provincial level, were meticulously analyzed. Age-standardized incidence rates (ASR) are calculated, and different regression models are used to identify significant variables associated with BC incidence. Spatial analysis techniques, including global and local Moran's index, geographically weighted regression, and Emerging hotspot analysis, were utilized to examine geospatial patterns, identify clustering and hotspots, and assess spatiotemporal distribution of BC incidence. RESULTS: The findings reveal that BC predominantly affects women (98.03%), with higher incidence rates among those aged 50 to 79. Isfahan (ASR = 26.1) and Yazd (ASR = 25.7) exhibit the highest rates. Significant predictors of BC incidence, such as marriage, tertiary education attainment rate, physician-to-population ratio, and PM2.5 air pollution, are identified through regression models. CONCLUSION: The study's results provide valuable information for the development of evidence-based prevention strategies to reduce the burden of BC in Iran. The findings underscore the importance of early detection, health education campaigns, and targeted interventions in high-risk clusters and adjacent regions. The geospatial insights generated by this study have implications for policy-makers, researchers, and public health practitioners, facilitating the formulation of effective BC prevention strategies tailored to the unique epidemiological patterns in Iran.

Design of highly sensitive nano-biosensor for diagnosis of hydatid cyst based on gold nanoparticles.

Cystic echinococcosis, a zoonotic parasitic infection, is a major public health and economic concern, with worldwide distribution. The development of sensitive diagnostic methods for hydatid disease is important. We designed a highly sensitive nano-biosensor for the diagnosis of hydatid cyst based on gold nanoparticles (AuNPs). AuNPs were synthesized. Echinococcus granulosus antigen was coated on the ELISA microwells. Then, the E. granulosus IgG antibody was added to the microwells. After incubation and washing, the Ag-Ab complex was incubated with a human IgG HRP​-conjugated antibody. Then, the synthesized AuNPs and tetramethylbenzidine (TMB), as a chromogenic substrate of HRP, were added to the reaction. Finally, the absorption rate was measured by spectrophotometry. The results showed that the enzyme peroxide and TMB change the color of the reaction from red to yellow by oxidizing AuNPs. The sensitivity and specificity of the designed method were investigated. The linear equation and regeneration of nanobiosensor designed for red color Y = 0.0312X + 0.649, R2 9962 and for yellow color Y = 0.013X + 0.398, R2 9851 were determined. The limit of detection of the designed nanobiosensor was 0.001 µg mL-1. The results confirmed that the designed nanobiosensor was completely specific for the detection of E. granulosus antibody.

High frequency of enterotoxigenic Bacteroides fragilis and Enterococcus faecalis in the paraffin-embedded tissues of Iranian colorectal cancer patients.

BACKGROUND: The association between specific bacteria and colorectal cancer (CRC) has been proposed. Only a few studies have, however, investigated this relationship directly in colorectal tissue with conflicting results. So, we aimed to quantitate Streptococcus gallolyticus, Fusobacterium spp, Enterococcus faecalis and enterotoxigenic Bacteroides fragilis (ETBF) in formalin-fixed and paraffin-embedded (FFPE) colorectal tissue samples of Iranian CRC patients and healthy controls. METHODS: A total of 80 FFPE colorectal tissue samples of CRC patients (n = 40) and healthy controls (n = 40) were investigated for the presence and copy number of above bacterial species using quantitative PCR. Relative quantification was determined using ΔΔCT method and expressed as relative fold difference compared to reference gene. RESULTS: Relative abundance and copy number of E. faecalis and ETBF were significantly higher in CRC samples compared to control group. E. faecalis was more prevalent than ETBF in tumor samples. Frequency of ETBF and E. faecalis in late stages (III/IV) of cancer was significantly higher than early stages (I/II). We did not detect a significant difference in abundance of S. gallolyticus and Fusobacterium spp between two groups. CONCLUSION: Our study revealed the higher concentration of E. faecalis and ETBF in FFPE samples of CRC patients than controls. However, additional investigations on fecal and fresh colorectal cancer tissue samples are required to substantiate this correlation.

Cancer in Iran 2008 to 2025: Recent incidence trends and short-term predictions of the future burden.

Policymakers require estimates of the future number of cancer patients in order to allocate finite resources to cancer prevention, treatment and palliative care. We examine recent cancer incidence trends in Iran and present predicted incidence rates and new cases for the entire country for the year 2025. We developed a method for approximating population-based incidence from the pathology-based data series available nationally for the years 2008 to 2013, and augmented this with data from the Iranian National Population-based Cancer Registry (INPCR) for the years 2014 to 2016. We fitted time-linear age-period models to the recent incidence trends to quantify the future cancer incidence burden to the year 2025, delineating the contribution of changes due to risk and those due to demographic change. The number of new cancer cases is predicted to increase in Iran from 112 000 recorded cases in 2016 to an estimated 160 000 in 2025, a 42.6% increase, of which 13.9% and 28.7% were attributed to changes in risk and population structure, respectively. In terms of specific cancers, the greatest increases in cases are predicted for thyroid (113.8%), prostate (66.7%), female breast (63.0%) and colorectal cancer (54.1%). Breast, colorectal and stomach cancers were the most common cancers in Iran in 2016 and are predicted to remain the leading cancers nationally in 2025. The increasing trends in incidence of most common cancers in Iran reinforce the need for the tailored design and implementation of effective national cancer control programs across the country.

Promoter Hypermethylation of Wnt/ß-catenin Signaling Pathway Inhibitor WIF-1 Gene and its Association with MTHFR C677T Polymorphism in Patients with Colorectal Cancer.

OBJECTIVES: Colorectal cancer (CRC) is a common malignancy with a high rate of mortality. The dysregulation of genes involved in the Wnt/ß-catenin signaling pathway is a common finding in cancers. Wnt-inhibitory factor-1 (WIF-1) suppresses the Wnt/ß-catenin signaling pathway and its inactivation by genetics and epigenetic changes may cause cancer. We investigated the DNA methylation status of the WIF-1 gene in patients with CRC and its interaction with MTHFR C677T polymorphism, a known modifier of methylation reaction. METHODS: We investigated 50 cancerous tissues and the adjacent non-cancerous tissue. Genomic DNA was extracted using a commercial kit and was treated by sodium bisulfite. Methylation-specific PCR was used for methylation analysis, and restriction fragment length polymorphism PCR to analyze the C677T polymorphism of the MTHFR gene. RESULTS: The frequency of WIF1 promoter DNA methylation was significantly higher in cancerous tissue than adjacent non-cancerous tissue (52.0% vs. 8.0%; p < 0.001). WIF1 promoter DNA methylation status showed a significant association only with tumor location (p = 0.009). Carriers of TT genotype and T allele of MTHFR C677T polymorphism had a significantly higher frequency of unmethylated WIF1 gene than methylated WIF-1 gene in cancerous tissue (p = 0.025 and p = 0.001, respectively). CONCLUSIONS: Promoter DNA hypermethylation of the WIF-1 gene is a significant risk factor for CRC development, which was significantly associated with tumor location only. The significant association of TT genotype and T allele of MTHFR C677T polymorphism with unmethylated WIF-1 gene suggests a protective role for this common polymorphism against methylation-induced development of CRC.

Investigating the methylation status of DACT2 gene and its association with MTHFR C677T polymorphism in patients with colorectal cancer.

Colorectal cancer (CRC) is one of the common causes of cancer death in Iranian population. Both genetic and epigenetic changes have been implicated in CRC pathogenesis. DACT2 gene as one of the WNT signaling pathway inhibitor was shown to display tumor suppressor activity in many cancers. The aim of present study was to investigate the methylation status of DACT2 gene and its association with methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in CRC patients. Fifty formalin-fixed paraffin-embedded cancerous and adjacent healthy tissues obtained from CRC patient were investigated. Genomic DNA was isolated using a FFPE commercial DNA extraction kit. The methylation status was evaluated by methylation specific PCR. Genotyping of MTHFR C677T polymorphism was performed using PCR-RFLP technique. Statistical analysis was done by GraphPad Prism 8. Results indicated that the frequency of methylated DACT2 gene was significantly higher in cancerous tissue relative to adjacent healthy tissue (P<0.001). DACT2 gene methylation was significantly more common among carriers of MTHFR 677CC genotype (P=0.035) and significantly less common among carriers of MTHFR 677T allele (P value =0.006). In conclusion the present study identified DACT2 gene methylation as a significant risk factor for CRC development. Moreover, the low frequency of DACT2 gene methylation among carriers of MTHFR 677T allele may confer a protective role for this common polymorphism against CRC risk.

Cancer incidence in Iran in 2014: Results of the Iranian National Population-based Cancer Registry.

BACKGROUND: We aimed to report, for the first time, the results of the Iranian National Population-based Cancer Registry (INPCR) for the year 2014. METHODS: Total population of Iran in 2014 was 76,639,000. The INPCR covered 30 out of 31 provinces (98% of total population). It registered only cases diagnosed with malignant new primary tumors. The main sources for data collection included pathology center, hospitals as well as death registries. Quality assessment and analysis of data were performed by CanReg-5 software. Age standardized incidence rates (ASR) (per 100,000) were reported at national and subnational levels. RESULTS: Overall, 112,131 new cancer cases were registered in INPCR in 2014, of which 60,469 (53.9%) were male. The diagnosis of cancer was made by microscopic confirmation in 76,568 cases (68.28%). The ASRs of all cancers were 177.44 and 141.18 in male and female, respectively. Cancers of the stomach (ASR = 21.24), prostate (18.41) and colorectum (16.57) were the most common cancers in men and the top three cancers in women were malignancies of breast (34.53), colorectum (11.86) and stomach (9.44). The ASR of cervix uteri cancer in women was 1.78. Our findings suggested high incidence of cancers of the esophagus, stomach and lung in North/ North West of Iran. CONCLUSION: Our results showed that Iran is a medium-risk area for incidence of cancers. We found differences in the most common cancers in Iran comparing to those reported for the World. Our results also suggested geographical diversities in incidence rates of cancers in different subdivisions of Iran.

Patients With Invasive Ductal Carcinoma Have Reduced Levels of Decorin Expression in Their Breast Tissue Compared to Patients With Fibroadenoma While Plasma Decorin Remains Unchanged.

BACKGROUND: Reduction in the level of tissue decorin is a hallmark of many types of cancer including breast carcinoma. However, reduced decorin expression has also been reported in several types of benign tumors to the extent that it has been proposed as a tissue marker to differentiate malignant from benign tumors. The aim of this study was to investigate the potential role of plasma decorin to distinguish breast cancer from fibroadenoma, the second most common type of benign tumor, after fibrocystic disease. METHODS: From 35 patients recruited in this study, 24 were affected with invasive ductal carcinoma, either grade II (n = 14) or grade III (n = 10). The other 11 patients had fibroadenoma lesions in their breasts. Tissue decorin mRNA and protein levels were assessed with real-time qPCR and Immunohistochemical analysis. ELISA was employed to measure plasma levels of decorin. RESULTS: The mean plasma decorin in cancer patients was measured to be 5.42 ± 1.83 ng/mL while fibroadenoma patients had an average of 4.22 ± 1.17 ng/mL decorin in their plasma. The difference was not significant. However, the mean expression level of decorin mRNA calculated by the 2-ΔΔCt method was 5.6-fold lower in the biopsied tissue specimens of IDC patients versus fibroadenoma, as expected. Consistent reduction in protein abundance was observed in the studied tissue sections. CONCLUSION: We have shown that tissue decorin is a reliable marker, unaffected by patient disease stage, to differentiate IDC from fibroadenoma. However, plasma decorin does not seem to have diagnostic value in this regard.

Human Papilloma Virus Genotype Distribution in Cervical lesions in Zanjan, Iran

Objective: Cervical cancer is one of the most common cancers among women all over the world, and main cause is persistent infection with high risk human papillomavirus (HPV) strains. It has been reported that the distribution and prevalence of HPV types varies by geographical region, so that this is important for prevention by type-specific vaccines. The aim of current study was to determine the genotype distribution of HPV using the INNO-LiPA genotyping assay in Zanjan province, North West Iran. Methods: A total of 112 formalin-fixed paraffin embedded (FFPE) tissue samples from cases of low-grade intraepithelial lesion (LSIL), high-grade intraepithelial lesion (HSIL) and squamous cell carcinoma (SCC) were collected. The polymerase chain reaction (PCR) was used to amplify DNA for genotyping. Results: Among the 112 samples from females (ranging from 20 to 69 years, mean age 43.8 ± 10.1) tested for HPV DNA, 50 samples were positive. Based on results of genotyping, most common HPV genotypes were HPV18 (48%) followed by HPV-6 (24%), HPV73 (16%), HPV-51(8%), HPV-31(8%), HPV-16 (8%), HPV-56 (4%), HPV-44 (4%). Conclusion: While HPV infection is the major etiological factor for cervical cancer, presence was relatively low in our survey. In the positive cases, however, HPV18 was the most common in line with many other populations. The fact that types vary among different populations must clearly be taken into account in design of vaccines for our country.

Prevalence and Associated Factors of Genital and Sexually Transmitted Infections in Married Women of Iran.

OBJECTIVES: This study aimed to determine the prevalence of genital and sexually transmitted infections and its related factors in married women in Iran. METHODS: We conducted a cross-sectional study of 4 274 married women living in urban and rural areas of the Zanjan province from 2012 to 2013. We used stratified cluster sampling to select the participants. Data collection included demographic characteristics, reproductive status, and cervical cytology results. RESULTS: The prevalence of lower genital infections and sexually transmitted infections were 20.1% and 7.4%, respectively. The most common vaginal infection was bacterial vaginosis with a prevalence of 8.5%, and the most common sexually transmitted infection was Trichomonas vaginalis (1.4%). The use of the intrauterine device (IUD) as a contraceptive, living in an urban area, and experiencing vaginal discharge were significantly related to genital tract and sexually transmitted infections. CONCLUSIONS: There was a high prevalence of genital infection among women living in Zanjab. Screening and treatment of genital infection are necessary to prevent adverse consequences in women who use an IUD or live in urban areas.

Prevalence of Abnormal Papanicolaou Test Results and Related Factors among Women Living in Zanjan, Iran.

BACKGROUND: Currently, a comprehensive program for screening and early detection of cervical cancer does not exist in Iran. This study aimed to determine the prevalence of abnormal Papanicolaou (Pap) smears and some related factors among women living in Zanjan, Iran. MATERIALS AND METHODS: This cross-sectional study was conducted in 2012 in Zanjan on 4274 married women aged 20-65 years. The study participants were selected through two-stage cluster sampling. After obtaining written consent, demographic and fertility questionnaires were completed. Samples from cervix were obtained through a standard method using the Rover Cervex- Brush. Evaluation and interpretation of the samples were reported using the Bethesda 2001 method. Data were statistically analyzed using chi-square and logistic regression models. RESULTS: Most inflammatory changes in the samples were mild (37.4%). Abnormal atypical changes in the epithelial cells were found in 4.04%. The highest percentage of abnormal changes in the epithelial cells was atypical squamous cells of undetermined significance (ASCUS) (1.9%). Abnormal results of Pap smear was significantly and independently associated with age, papillomavirus infection, and lack of awareness about Pap smear tests. CONCLUSIONS: Given the high prevalence of inflammatory and precancerous changes in this study, compared to other studies in Iran and other Muslim countries, and the effect of demographic variables and individual factors on abnormal results, increasing the awareness of women and their families regarding the risk factors for cervical cancer, preventive measures such as screening, and timely treatment seem necessary.