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Blood-Based vs. Tissue-Based mRNA Expression of Thymidylate Synthase, Dihydropyrimidine Dehydrogenase, and Methylenetetrahydrofolate Reductase: A Prospective Study to Predict the Neoadjuvant CAPEOX Response in Advanced Colorectal Cancer

Asian Pac J Cancer Prev. 2026 Jun 1;27(6):2269-2278. doi: 10.31557/APJCP.2026.27.6.2269.

ABSTRACT

BACKGROUND: Fluoropyrimidine-based chemotherapy is a fundamental treatment for colorectal cancer (CRC), yet its therapeutic efficacy is often limited by significant inter-individual variability. Enzymes involved in 5-fluorouracil (5-FU) metabolism thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and methylenetetrahydrofolate reductase (MTHFR) are critical determinants of drug response. This study aimed to evaluate the molecular correlation between TS, DPD, and MTHFR mRNA expression in paired tumor tissue and peripheral blood samples, while simultaneously developing and validating a non-invasive predictive nomogram to forecast therapeutic response to neoadjuvant CAPEOX (capecitabine-oxaliplatin) chemotherapy in advanced CRC.

METHODS: A prospective cohort study was conducted on 36 patients with stage III-IV CRC receiving CAPEOX. mRNA expression of TS, DPD, and MTHFR was quantified using qRT-PCR from paired tumor and peripheral blood samples. Chemotherapy response was evaluated using RECIST 1.1 criteria. Statistical analyses included Spearman correlation, the Mann-Whitney U test, and multivariate logistic regression. A nomogram was constructed based on significant predictors.

RESULTS: DPD and MTHFR expression levels were significantly lower in responders than in non-responders (p < 0.001), while TS expression showed no significant difference. Gene expression in tissue and blood was strongly correlated (r = 0.820 for TS, r = 0.658 for DPD, and r = 0.623 for MTHFR; all p < 0.001). Multivariate analysis identified blood-based DPD and MTHFR expression as independent predictors of response. The predictive nomogram demonstrated excellent discrimination (AUC = 0.932).

CONCLUSION: Lower DPD and MTHFR expression predicts a favorable response to neoadjuvant CAPEOX in advanced CRC. These biomarkers offer a promising, non-invasive approach to personalizing treatment strategies potentially enhancing therapeutic efficacy while minimizing unnecessary toxicity.

PMID:42345176 | DOI:10.31557/APJCP.2026.27.6.2269

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Molecular and Lifestyle Determinants of Oral Squamous Cell Carcinoma in Bangladesh: Dietary Patterns Independent of HPV and TERT Promoter Mutations

Asian Pac J Cancer Prev. 2026 Jun 1;27(6):2259-2268. doi: 10.31557/APJCP.2026.27.6.2259.

ABSTRACT

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the sixth most prevalent cancer globally and constitutes a major public health burden in Bangladesh, with approximately 7.5% of all cancer-related deaths. Although tobacco and betel-quid use are recognized risk factors, dietary patterns may also contribute to OSCC development.

OBJECTIVE: This study investigated the association of lifestyle and dietary factors with OSCC in Bangladeshi patients and explored the potential involvement of TERT promoter mutations and human papillomavirus (HPV) infection.

METHODS: A hospital-based, case-control study was conducted involving 47 histopathologically confirmed OSCC patients and 100 age- and sex-matched healthy controls without cancer or chronic illness. Sociodemographic, lifestyle, and dietary data were collected through a structured questionnaire. Tumor DNA was analyzed for TERT promoter mutations and HPV DNA using PCR and Sanger sequencing. Statistical analyses were performed using multivariable logistic regression to identify significant associations.

RESULTS: Excessive betel-quid chewing was strongly associated with OSCC (p < 0.01). Among 39 sequenced OSCC samples, 25 single-nucleotide polymorphisms (SNPs) at position -245 (A>G) and one hotspot mutation at position -124 (G>A) of the TERT promoter were identified substantially lower than frequencies reported in other populations. No HPV DNA was detected in any sample. Certain dietary patterns such as low fruit and vegetable intake and high consumption of betel quid were linked to increased OSCC risk.

CONCLUSION: Our findings suggest that, in Bangladeshi patients, specific dietary and lifestyle factors, rather than HPV infection or TERT promoter mutations, contribute significantly to OSCC development. Targeted public health strategies emphasizing nutritional awareness and cessation of betel-quid use are recommended.

PMID:42345175 | DOI:10.31557/APJCP.2026.27.6.2259

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Combined Diagnostic Utility of Serum CA15-3 and Routine Hematological Indicators for Breast Cancer Differentiation in an Iraqi Cohort

Asian Pac J Cancer Prev. 2026 Jun 1;27(6):2251-2258. doi: 10.31557/APJCP.2026.27.6.2251.

ABSTRACT

BACKGROUND: Breast cancer (BC) is a leading cause of mortality among Iraqi women, underscoring the need for accessible diagnostic tools. This study evaluates the combined utility of the tumor marker CA15-3 and routine hematological parameters as an adjunctive tool for distinguishing between treatment-naïve BC patients with a pre-existing diagnosis and healthy individuals.

METHODS: In this case-control study, 100 female BC patients (Group I) and 50 healthy controls (Group II) were recruited. Serum CA15-3 levels were measured using electrochemiluminescence immunoassay (ECLIA), and a complete blood count was performed. Statistical analyses included independent t-tests, ROC curve analysis, and logistic regression to develop a combined diagnostic model. All BC patients were treatment-naïve and were required to submit blood samples prior to undergoing any surgical procedure, although they had already been diagnosed.

RESULTS: CA15-3 levels were significantly higher in BC patients (26.1 ± 7.5 U/mL) than in controls (7.54 ± 2.6 U/mL; P < 0.001). Significant differences were also observed in white blood cell (WBC), red blood cell (RBC), lymphocyte, and platelet counts (all P < 0.05). ROC analysis showed excellent diagnostic performance for CA15-3 alone (AUC = 0.98). A combined model integrating CA15-3 with the four hematological parameters achieved a superior AUC of 0.99, with 96% sensitivity and specificity.

CONCLUSION: Elevated CA15-3 is confirmed as a key diagnostic marker for BC. Integrating CA15-3 with specific, routinely measured hematological indicators provides an improved, accessible, and cost-effective adjunctive tool for differentiating treatment-naïve BC patients from healthy individuals. This approach may be particularly useful for triaging patients with suspicious symptoms or monitoring those with established diagnoses.

PMID:42345174 | DOI:10.31557/APJCP.2026.27.6.2251

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Melatonin Receptors in Uterine Leiomyomas: An Immunohistochemical Study

Asian Pac J Cancer Prev. 2026 Jun 1;27(6):2203-2210. doi: 10.31557/APJCP.2026.27.6.2203.

ABSTRACT

BACKGROUND: Uterine leiomyomas are the most common benign tumors in women of reproductive age, often causing significant symptoms such as abnormal bleeding, pain, and infertility. Melatonin, a hormone with anti-proliferative and oncostatic properties, has been studied; however, its effects on uterine leiomyomas remain unclear.

OBJECTIVE: This study aimed to evaluate the immunohistochemical expression of melatonin receptors MT1 and MT2 in uterine leiomyomas compared to normal myometrium, and to correlate their expression with clinical and histopathological features.

METHODS: A case-control study was conducted on ninety cases retrieved (60 leiomyoma cases, thirty normal myometrium controls). Immunohistochemical staining was performed to assess the expression of MT1 and MT2 receptors. Clinical data were collected, and statistical analyses were conducted to evaluate associations between receptor expression and demographic, clinical, and histological features.

RESULTS: MT1 and MT2 were significantly overexpressed in leiomyomas compared to controls (MT1: 70% vs. 30%, p < 0.0001; MT2: 60% vs. 16.7%, p < 0.0001). A strong positive correlation was observed between MT1 and MT2 expression (r = 0.6, p < 0.0001). MT1 score varied significantly with age (p = 0.03), tumor location (p = 0.04), and presenting symptoms (p = 0.03), while MT2 expression was positively associated with the number of lesions (p = 0.033).

CONCLUSION: Melatonin receptors MT1 and MT2 are significantly upregulated in uterine leiomyomas, suggesting a potential role in their pathogenesis. These findings support further investigation into melatonin-based therapies as adjunctive treatments for leiomyomas.

PMID:42345168 | DOI:10.31557/APJCP.2026.27.6.2203

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Novel Anticancer Mechanism of Chamuangone through the Inhibition of Oncogenic Protein-Driven Oxidative Stress

Asian Pac J Cancer Prev. 2026 Jun 1;27(6):2189-2201. doi: 10.31557/APJCP.2026.27.6.2189.

ABSTRACT

OBJECTIVE: To evaluate the anticancer mechanisms of Chamuangone against cholangiocarcinoma (CCA) cells.

METHODS: Chamuangone was tested for cytotoxicity against KKU-100 and KKU-452 cells for 24 and 48 h. Apoptosis, cell proliferation, mitochondrial membrane potential, and intracellular reactive oxygen species (ROS) levels were assessed using Annexin V, Ki-67, JC-1 assays, and DCFH-DA fluorescence probe, respectively. Oncology proteins expression was measured.

RESULTS: Chamuangone inhibited CCA cell growth in a dose- and time- dependent manner, with IC50 values in KKU- 100 cells of 1.175 and 0.331 μg/mL at 24 and 48 hours, respectively; in KKU- 452 cells, the IC50 values were 1.208 and 0.428 μg/mL. Consequently, Chamuangone at 1.5 and 3.0 μg/mL effectively induced both early and late apoptosis in a statistically significant manner, which correlated with a marked reduction in cell proliferation, as evidenced by the decrease in Ki-67 positive populations to 49.04% and 17.02%, respectively. Chamuangone at concentrations of 0.75, 1.5, and 3.0 μg/mL significantly induced mitochondrial dysfunction by reducing the Red/Green fluorescence ratio across all time points (3-24 h), indicating a loss of mitochondrial membrane potential that triggers apoptosis. The induction of intracellular oxidative stress was indicated by a significant increase in the high-dose group of Chamuangone. Moreover, it also suppressed the expression of key ROS- and oxidative stress-associated oncogenic proteins, including Carbonic Anhydrase IX, Enolase2, CXCL8/IL-8, Galectin-3, EGFR/ErbB1, Progranulin, FGF basic, Dkk-1, p27/kip1, Mesothelin, Survivin, leading to redox imbalance and apoptosis in KKU-100 cells.

CONCLUSION: Chamuangone inhibits CCA cell proliferation by inducing apoptosis through mechanisms involving the suppression of the Ki67, loss of mitochondrial membrane potential, intracellular ROS accumulation, and downregulation of oncogenic-related proteins involved in proliferation, survival, angiogenesis, and oxidative stress. Thus, Chamuangone has significant potential as a lead compound for the development of novel CCA therapeutics.

PMID:42345167 | DOI:10.31557/APJCP.2026.27.6.2189

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MUC5AC Protein Expression as a Potential Predictor of Metastasis in Mucinous Ovarian Carcinoma: Unveiling a New Biomarker in a Rare Cancer Subtype

Asian Pac J Cancer Prev. 2026 Jun 1;27(6):2157-2162. doi: 10.31557/APJCP.2026.27.6.2157.

ABSTRACT

BACKGROUND: Mucinous ovarian carcinoma (MOC) is a distinct and lethal histological subtype of ovarian cancer, frequently characterized by late-stage diagnosis and chemoresistance. The role of MUC5AC a gel-forming mucin associated with aggressive behavior in various epithelial malignancies remains under-investigated in the context of MOC metastasis, particularly within Indonesian populations. This study aimed to evaluate the correlation between MUC5AC expression and metastatic occurrence in MOC to determine its utility as a predictive biomarker.

METHODS: A retrospective analysis was conducted on 63 MOC tissue samples, collected between 2021 and 2024. MUC5AC expression was evaluated via immunohistochemistry (IHC) using a semi-quantitative scoring system. Statistical associations were determined using the Chi-square test, with an emphasis on calculating the odds ratio (OR) for metastatic risk.

RESULTS: Among the 63 cases, metastatic involvement (omental or extra-ovarian) was identified in 37 samples (58.7%). A significant correlation was noted between high MUC5AC expression and the occurrence of metastasis in MOC (p=0.002). Furthermore, tumors exhibiting high MUC5AC expression demonstrated a 6.4-fold increased probability of metastasis compared to those with low expression (OR = 6.40; 95% CI: 1.89-21.5).

CONCLUSION: Elevated MUC5AC expression is significantly correlated with metastatic involvement in primary MOC. These findings suggest that MUC5AC has the potential to serve as a predictive biomarker for metastasis in this rare cancer subtype, potentially assisting in the identification of patients who require more intensive staging and surveillance.

PMID:42345163 | DOI:10.31557/APJCP.2026.27.6.2157

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Refrigerator Ownership and the Decline of Gastric Cancer: A Global Overview

Asian Pac J Cancer Prev. 2026 Jun 1;27(6):2143-2148. doi: 10.31557/APJCP.2026.27.6.2143.

ABSTRACT

OBJECTIVE: Refrigeration of food has been shown to mitigate environmental and dietary risk factors important in the pathogenesis of gastric cancer. Globally, the incidence of gastric cancer has decreased. This study aims to determine the relationship between refrigerator ownership and gastric cancer.

METHODS: Gastric cancer data were obtained from the Global Burden of Disease study, and refrigerator ownership data were sourced from GlobalDataLab. Countries were excluded from the analysis if they lacked refrigerator ownership data for more than 10 years or had over 80% ownership at the start of data collection. The relationship between the two variables was assessed using Spearman’s rank correlation coefficient.

RESULT: Countries were screened using the inclusion criteria, and 85 countries from five continents were included in the study. Seventy-three countries demonstrated a negative correlation between refrigerator ownership and gastric cancer among their male populations, and 55 countries showed comparable results among their female populations. Thirteen countries exhibited a positive correlation between the two variables.

CONCLUSION: Increasing refrigerator ownership appears to be associated with decreasing gastric cancer rates. Further research is needed to identify the specific risk factors involved in gastric cancer pathogenesis in the 13 countries where this association was not observed.

PMID:42345161 | DOI:10.31557/APJCP.2026.27.6.2143

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Cancer Knowledge and Environmental Exposure Awareness Among Healthcare Workers and the General Public in Istanbul: A Cross-Sectional Study

Asian Pac J Cancer Prev. 2026 Jun 1;27(6):2107-2116. doi: 10.31557/APJCP.2026.27.6.2107.

ABSTRACT

OBJECTIVES: A substantial proportion of cancers are preventable, yet awareness of risk factors and screening remains limited. This study assessed disparities in knowledge of cancer epidemiology, screening, and environmental risk factors between healthcare workers(HCWs) and the general public(GP) in two urban districts of Istanbul, and identified associated sociodemographic and behavioral determinants.

METHODS: A cross-sectional survey was conducted with 309 participants using a structured 42-item questionnaire covering cancer epidemiology (15 items), screening (9), and environmental risk factors(18). Each correct response scored one point. Internal consistency was high (Cronbach’s alpha = 0.944). Knowledge levels were analyzed across subgroups.

RESULTS: HCWs scored significantly higher than the GP in all domains: epidemiology (7.7 ± 3.6; 6.4 ± 2.8), screening (5.2 ± 2.7; 2.6 ± 2.1), and environmental risks (12.5 ± 5.0; 10.7 ± 5.7). Higher education, better income, and health-promoting behaviors were associated with increased knowledge. Despite this, notable gaps persisted. Breast cancer was widely recognized (86.1% HCWs; 81.9% GP), whereas awareness of lethal cancers like liver cancer was low (12.2% HCWs; 4.6% GP). Screening knowledge varied: HCWs were more aware of breast cancer screening; prostate and lung cancer screening were poorly recognized, particularly by the GP. While radiation risks were commonly known, links between smoking and non-lung cancers were largely unknown.

CONCLUSION: Despite national programs, critical gaps in knowledge persist across all domains, including among HCWs. These disparities, shaped by education, income, and behavior, undermine prevention efforts. Tailored education strategies are needed to improve knowledge, especially environmental cancer literacy, and promote early detection in both groups.

PMID:42345157 | DOI:10.31557/APJCP.2026.27.6.2107

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Assessment of Total Delays and Their Associated Factors among Breast, Cervical, and Head and Neck Cancers in Northwestern India: A Cross-Sectional Study

Asian Pac J Cancer Prev. 2026 Jun 1;27(6):2097-2105. doi: 10.31557/APJCP.2026.27.6.2097.

ABSTRACT

BACKGROUND: Timely diagnosis and treatment are critical for improving cancer survival; however, significant delays persist across the cancer care continuum, particularly in resource-constrained settings like India. This study aimed to analyze the extent and patterns of delays among patients with breast, cervical, and head and neck cancers in northwestern India.

METHODS: This exploratory cross-sectional study included all histopathologically confirmed cases of the three cancer types who initiated radiotherapy at the Radiotherapy Department of Government Medical College, Amritsar, during December 1, 2023, to November 30, 2024. Data on sociodemographic profiles, clinical details, and treatment timelines were collected through interviews and medical records. Delays were categorized as appraisal, help-seeking, diagnostic, pre-treatment, system, and total delays. Analysis was conducted at the descriptive, bivariate, and multivariable levels. Median delays and interquartile ranges were calculated for each cancer type. Differences in delay intervals between cancer groups were assessed using the Kruskal-Wallis H test, and differences between two-category variables were assessed using the Mann-Whitney U test. Associations between categorical variables and the presence of prolonged total delay (≥120 days) were examined using the chi-square test or Fisher’s exact test, as appropriate. Correlation between total delay and number of medical contacts was evaluated using Spearman’s rank correlation coefficient. Finally, multivariable binary logistic regression was performed to identify independent predictors of prolonged total delay, and adjusted odds ratios with 95% confidence intervals were reported. A p-value of <0.05 was considered statistically significant.

RESULTS: Among the 119 patients included in the study (45 breast, 28 cervical, and 46 head and neck cancers), breast cancer patients experienced the longest total delay (median: 282 days), followed by cervical (median: 199 days) and head and neck cancers (median: 190 days). System delay was the primary contributor across all three cancer types, driven largely by diagnostic delays. Appraisal delay was longest for breast cancer (median 155.5 days), help-seeking delay was longest for head and neck cancer (median 65 days), and pre-treatment delay was also longest for breast cancer (median 51.5 days). Variations in delays were observed across sociodemographic factors, but none reached statistical significance.

CONCLUSION: This study highlights the need for a targeted, cancer-specific approach to address delays, with a focus on strengthening diagnostic services and improving system efficiency within the healthcare infrastructure. Implementing multi-pronged strategies for early detection, timely care, and prevention is crucial in reducing the cancer burden in this high-risk region.

PMID:42345156 | DOI:10.31557/APJCP.2026.27.6.2097

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Awareness of Cervical Cancer, Willingness, and Barriers to Cervical Cancer Screening among Women in Madurai: A Cross-Sectional Study in South India

Asian Pac J Cancer Prev. 2026 Jun 1;27(6):2053-2060. doi: 10.31557/APJCP.2026.27.6.2053.

ABSTRACT

OBJECTIVES: This study aims to investigate rural women’s knowledge and attitudes towards cervical cancer, their willingness to participate in cervical cancer screening, and the perceived obstacles to screening.

METHODOLOGY: A community-based cross-sectional study was conducted in Madurai district, Tamil Nadu, India, from February to July 2024, involving 350 women aged 25 to 65 years. Utilizing multistage random sampling, the study employed face-to-face interviews with a semi-structured questionnaire focused on knowledge and attitudes towards cervical cancer, as well as barriers to screening services. Data were analyzed using R programming (version 4.4.3).

RESULTS: Participants had a mean age of 33.83 ± 7.56 years, with 29.1% being illiterate. Only 15.7% had undergone cervical cancer screening. Approximately 68.3% and 66.8% expressed willingness to undergo cervical cancer screening if it were free or recommended by a doctor, respectively. Major barriers to screening included fear of falling sick after screening (65.1%), lack of awareness (64.3%), and the belief that screening is unnecessary at their age (64%). Women aged 35-44 years (3.21 ± 0.49, p = 0.05, β = -0.542), those who were non-working (3.14 ± 0.50, p = 0.02, β = -0.739), illiterate (3.21 ± 0.57, p = 0.04, β = -1.093), of lower socioeconomic class (3.09 ± 0.52, p = 0.05, β = -0.883), and those who had never undergone cervical cancer screening (3.07 ± 0.52, p = 0.02, β = -0.677) had significantly lower mean knowledge scores.

CONCLUSION: The research highlights significant gaps in awareness and screening among rural women in Madurai, despite a positive attitude towards screening. Low participation rates stem from educational and socioeconomic barriers. The study’s regional focus may limit broader applicability, and social desirability bias may be a concern due to the use of interviewer-administered questionnaires. Enhancing the Makkalai Thedi Maruthuvam program in Tamil Nadu with targeted education and community involvement could boost awareness and screening rates.

PMID:42345151 | DOI:10.31557/APJCP.2026.27.6.2053