Journal of Cancer Prevention最新文献

Limited epidemiologic evidence links cancer risk to dietary acid load and methionine intake. Acid stress and metabolic acidosis are closely related to cancer development. Methionine is the main acidogenic amino acid and exerts epigenetic influences. We recently reported preliminary results on dietary acid load, methionine intake, and breast cancer risk. Therefore, both variables deserve further epidemiologic analysis. We revisited a Uruguay-based case-control study (572 cases/2,294 matched controls); women were recruited from 4 central hospitals, and all were interviewed using a specific questionnaire. Food-derived nutrients were calculated from available databases. Dietary acid load was estimated based on a validated formula: the potential renal acid load (PRAL) score. OR was estimated by logistic regression, adjusting for potential confounders. We found significant, direct associations between the breast cancer risk and PRAL (OR = 3.33) and methionine intake (OR = 5.87). Trends were significant (P < 0.001). PRAL and methionine displayed higher ORs among subsets with a positive family history of cancer compared to a negative one: OR = 6.16 vs. 2.80 (PRAL); OR = 11.8 vs. 4.86 (methionine). Both estimates were higher in pre- than postmenopausal women: OR = 5.91 vs. 2.96 (PRAL); OR = 8.76 vs. 5.39 (methionine). In conclusion, an acidogenic dietary style may increase a breast cancer risk. Furthermore, our findings suggest that methionine intake, showing comparable or even higher ORs than the dietary acid load scores themselves, might influence the risk associated with acid-base imbalance, ultimately leading to cancer. Additional research on methionine-induced epigenetic influences is warranted.

Lung cancer remains one of the most prevalent and lethal malignancies worldwide. Most cases are caused by non-small-cell lung cancer (NSCLC). Over the past three decades, the treatment landscape of NSCLC has been profoundly reshaped by the discovery of epidermal growth factor receptor (EGFR) mutations and the subsequent development of EGFR-targeted therapies. This review provides a comprehensive overview of the evolution of four generations of EGFR tyrosine kinase inhibitors (EGFR-TKIs): first-generation reversible inhibitors such as gefitinib and erlotinib; second- and third-generation irreversible inhibitors, including afatinib, dacomitinib, and osimertinib; and emerging fourth-generation agents, such as amivantamab. Each generation has contributed to efficacy improvement, central nervous system penetration, and resistance management. Despite remarkable advances in development of EGFR-TKIs, acquired resistance and tumor heterogeneity remain major challenges. Bioinformatic analyses using The Cancer Genome Atlas (TCGA) datasets highlight the high mutation frequency and clinical significance of EGFR alterations, underscoring their pivotal role in tumor progression and prognosis. Future studies should explore combination therapies, antibody-drug conjugates, and next-generation allosteric inhibitors as promising strategies to overcome resistance. The evolution of EGFR-targeted therapy exemplifies the progress of precision oncology and serves as a basis for designing new paradigms in the management of lung cancer.

This study aimed to examine differences in the association between reproductive factors and breast cancer (BC) risk across ethnic groups, particularly Asians and non-Asians, and to explore temporal trends through meta-analysis. The study focused on epidemiologic research published up to August 31, 2022, examining reproductive factors related to BC risk and family history. All effect sizes were calculated using a random-effect model. The protective effect of the higher number of childbirths against BC was stronger in Asians than in Europeans or Americans (childbirths ≥ 2 vs. 1; Asians, relative risk [RR]: 0.66, 95% CI: 0.59-0.74; Europeans, RR: 0.89, 95% CI: 0.86-0.92; Americans, RR: 0.91, 95% CI: 0.87-0.96). Similarly, the effect of high parity was more pronounced in Asians than in Americans and Europeans (Asians, RR: 0.72, 95% CI: 0.58-0.89; Europeans, RR: 0.81, 95% CI: 0.74-0.88; Americans, RR: 0.84, 95% CI: 0.76-0.92). In contrast, no significant differences among populations were found in BC risks associated with combined hormone replacement therapy use. While the association between family history and BC risk appeared to differ by ethnicity, no temporal change was observed (< 2010, RR: 1.58, 95% CI: 1.40-1.78; ≥ 2010, RR: 1.57, 95% CI: 1.46-1.67). These results suggest that some reproductive factors associated with BC differ across ethnicities and time trends, perhaps due to the prevalence of reproductive factors and the baseline hazard of BC.

This study aimed to determine the association between trajectories of obesity status and prediabetes reversion to normoglycemia or progression to diabetes. The study included 14,452 participants from the National Health Insurance Service-National Health Screening (NHIS-HEALS) cohort who continuously had prediabetes glycemic status during the index period (2002-2008), defined by their fasting plasma glucose. The exposure of the study was the trajectories of obesity (defined by body mass index ≥ 25 kg/m²) generated using latent class growth analysis. The outcomes were reversion to normoglycemia or progression to diabetes, whichever occurred first during the follow-up period (2009-2016). The association between trajectories and changes in prediabetes status were examined using cause-specific hazard regression by obtaining the hazard ratio (HR) with a 95% CI. We identified three distinct trajectories which were "Stable obese", "Stable non-obese" and "Obese to non-obese". After a median follow-up of 2 years, 51.99% of participants had their glycemic status back to normoglycemia and 32.17% developed diabetes. Compared with participants in the "Stable obese" group, those in "Stable non-obese" and "Obese to non-obese" groups were more likely to have reversion to normoglycemia (HR with a 95% CI = 1.30 [1.23-1.37] and 1.15 [1.07-1.24], respectively) and lower risk of developing diabetes (0.78 [0.73-0.84] and 0.90 [0.82-0.98], respectively). The findings suggest that maintaining or achieving a non-obese status is linked to higher reversion to normoglycemia as well as lower risks of developing diabetes.

Estrogen receptor alpha (ERα) defines the biology of estrogen receptor-positive breast cancer by regulating both tumor-intrinsic signaling and the surrounding immune microenvironment. Beyond its genomic and non-genomic actions, ERα modulates cytokine production, antigen presentation, and the activity of innate and adaptive immune cells, contributing to a low mutational burden, weak immunogenicity, and an immune-excluded tumor state. Through interactions with NF-κB, suppression of interferon pathways, and regulation of myeloid and lymphoid cell functions, ERα promotes immune tolerance and supports tumor progression. These immunoregulatory effects help explain limited responses to endocrine therapy and the poor performance of immune checkpoint inhibitors in ER-positive diseases. Emerging strategies, including next-generation selective estrogen receptor degraders and combinations with CDK4/6 inhibitors or immunotherapy, aim to overcome ERα-driven immune suppression. Understanding ERα-mediated immune regulation will be essential for developing more effective therapeutic approaches for ER-positive breast cancer.

Acquired resistance to tyrosine kinase inhibitors (TKIs), such as osimertinib, poses a major barrier to effective treatment of non-small cell lung cancer (NSCLC). Recent data suggest that lysosomal Ca²⁺ signaling, particularly via transient receptor potential mucolipin 3 (TRPML3; also known as MCOLN3), contributes to TKI resistance by promoting lysosomal exocytosis and drug efflux. Here, we investigated the regulatory role of microRNA-601 (miR-601) in modulating TRPML3 expression and its impact on osimertinib resistance in NSCLC. Bioinformatic predictions using the DIANA microT-CDS algorithm identified TRPML3 as a putative target of miR-601. Luciferase reporter assays confirmed direct binding of miR-601 to the TRPML3 3'-untranslated region. Functional assays were conducted with parental and osimertinib-resistant PC9 and HCC827 cells to evaluate the effects of miR-601 on TRPML3 expression, apoptosis, cell-cycle progression, and drug sensitivity. Osimertinib treatment led to a time-dependent miR-601 downregulation in NSCLC cells, and its basal expression remained suppressed in resistant sublines. miR-601 overexpression reduced TRPML3 protein levels, enhanced poly(ADP-ribose) polymerase cleavage, induced G0/G1 cell-cycle arrest, and restored osimertinib sensitivity. Similar effects were observed upon TRPML3 knockdown, supporting a TRPML3-dependent mechanism. Thus, miR-601 negatively regulates TRPML3 and modulated TKI responses in NSCLC cells. Restoring miR-601 expression may represent a promising therapeutic strategy for overcoming acquired osimertinib resistance by targeting TRPML3-mediated lysosomal signaling.

Colorectal cancer screening is an effective strategy to prevent disease, reduce the risk of advanced-stage diagnosis, and improve survival. Timely follow-up of abnormal screening results, particularly abnormal fecal immunochemical tests, is essential to realizing these benefits. This qualitative study examined routine processes related to colonoscopy referral and completion for patients of a federally qualified health center (FQHC) referred to community gastroenterology (GI) practices. Using a snowball sampling approach, five FQHC individuals and eight community GI practice individuals were interviewed. Interviews at the FQHC were conducted between March 2020 and September 2021, during the early phase of the coronavirus disease 2019 pandemic. Due to clinic closures and other pandemic-related disruptions, GI practice interviews occurred between August 2021 and January 2023. Study findings highlight the need for improved communication and collaboration between primary care and GI practices to support colonoscopy completion among low resource populations. Interviewees also offered recommendations to ensure colonoscopy completion. Further research is needed to pilot test centralized referral and scheduling systems and to develop multicomponent interventions that address both patient and organizational barriers to colonoscopy completion.

This study assessed sex disparities in the causes of death (CODs), both related to cancer and non-cancer, in a nationwide database of cancer survivors in South Korea. Our database included cancer cases diagnosed in Korea between 2009 and 2016, and their CODs up to 2021. Deaths were classified into three categories: index-cancer, non-index-cancer, and non-cancer causes. Male-to-female age-standardized mortality ratios (M/F SMRs) were computed by dividing the male-specific mortality rate by the corresponding female-specific rate. Out of a total of 279,104 (49.0%) recorded deaths in male survivors and 141,674 (27.9%) deaths in female survivors, the M/F SMRs showed an elevated mortality risk in males, both for cancer-related causes (1.46, 95% CI 1.45-1.47) and non-cancer CODs (1.75, 95% CI 1.74-1.77). Among non-cancer CODs, the most significant sex disparity in mortality risk was evident in deaths attributed to chronic lower respiratory diseases (CLRDs), with an SMR of 4.51 (95% CI 4.30-4.73), followed by mortalities due to intentional self-harm (suicide) (2.95, 95% CI 2.85-3.05) and transportation accidents (SMR 2.86, 95% CI 2.67-3.04). Subgroup analysis focusing on survivors of common cancer sites indicated a relatively consistent pattern in index cancer deaths, but the M/F SMRs for non-index cancer and non-cancer deaths demonstrated variability across different cancer sites. Our study underscores an overall elevated mortality risk in male cancer survivors compared to female counterparts. Although deaths stemming from primary cancer remain a substantial concern for both sexes, disparities in non-cancer deaths warrant considerable attention, particularly in relation to CLRD and intentional self-harm (suicide) among male survivors.

Africa has increasingly participated in clinical trials; however, there is limited literature on the trends of oncological clinical trial registration. This study aims to review the patterns of oncological clinical trials conducted in Africa between 2000 and 2024. Three major trial registries-Pan African Clinical Trial Registry (PACTR), ClinicalTrials.gov (CTG), and the International Standard Randomized Controlled Trial Number (ISRCTN)-were utilized. Data were extracted and analyzed descriptively using Microsoft Excel (Microsoft Corporation). CTG recorded the highest number of registered trials (n = 458), followed by PACTR (n = 148) and ISRCTN (n = 69). Egypt, Algeria, and South Africa contributed the most to these registrations. The number of trials gradually increased after 2010, peaking between 2018 and 2019. Randomized study designs were the most common, representing at least 80% of trials in the CTG and PACTR registries. Breast and cervical cancers were the most frequently studied cancer types, although few trials had published results. The completeness of trial information varied by registry: CTG (47.8%), PACTR (33.1%), and ISRCTN (84.1%). Only the ISRCTN registry consistently reported data on registration timing, whereas phases II and III were the most commonly represented trial phases in the CTG and ISRCTN registries. In conclusion, although there has been a gradual increase in oncological clinical trial activity in Africa, published outcomes remain limited. This study highlights the need to improve trial registration practices and promote the timely publication of results across the continent.

Human papillomavirus (HPV) is the most common sexually transmitted infection worldwide and a leading cause of several cancers, including cervical, anal, oropharyngeal, vulvar, vaginal, and penile cancers, as well as benign conditions such as genital warts. The global burden of HPV is particularly high in low- and middle-income countries due to disparities in vaccine accessibility, screening, and awareness. This review synthesizes recent advances in the primary and secondary prophylaxis of HPV-related diseases. Primary prophylaxis encompasses vaccination, education, and behavioral interventions. Although effective vaccines and gender-neutral vaccination policies exist, global uptake remains suboptimal, especially among males and in resource-limited settings. Different educational and school-based vaccination programs have demonstrated success in increasing coverage, while behavioral measures such as safe sexual practices, condom use, and male circumcision have been shown to reduce transmission risk. Secondary prophylaxis focuses on early detection and treatment of precancerous lesions, with HPV-DNA testing now the preferred method for cervical cancer screening, while standardized screening protocols for men are lacking. Treatment ranges from topical agents to excisional procedures and ablative therapies for cervical intraepithelial neoplasia and other precancerous lesions, depending on the type and severity. However, access to timely and effective treatment remains suboptimal in many regions. Addressing gaps in the primary and secondary prevention is essential for reducing the global impact of HPV and achieving international cancer prevention goals.