Elevated Cancer Risk Research Articles

The Significant Associations between Epigenetic Clocks and Bladder Cancer Risks.

Bladder cancer is an age-related disease, with over three-quarters of cases occurring in individuals aged 65 years and older. Accelerated biological aging has been linked to elevated cancer risks. Epigenetic clocks serve as excellent predictors of biological age, yet it remains unclear whether they are associated with bladder cancer risk. In this large case-control study, we assessed the associations between four well-established epigenetic clocks-HannumAge, HorvathAge, GrimAge, and PhenoAge-and bladder cancer risk. Utilizing single nucleotide polymorphisms (SNPs), which were identified in a genome-wide association study (GWAS), linked to these clocks as instruments, we constructed a weighted genetic risk score (GRS) for each clock. We discovered that higher HannumAge and HorvathAge GRS were significantly associated with increased bladder cancer risk (OR = 1.69 per SD increase, 95% CI, 1.44-1.98, p = 1.56 × 10-10 and OR = 1.09 per SD increase, 95% CI, 1.00-1.19, p = 0.04, respectively). Employing a summary statistics-based Mendelian randomization (MR) method, inverse-variance weighting (IVW), we found consistent risk estimates for bladder cancer with both HannumAge and HorvathAge. Sensitivity analyses using weighted median analysis and MR-Egger regression further supported the validity of the IVW method. However, GrimAge and PhenoAge were not associated with bladder cancer risk. In conclusion, our data provide the first evidence that accelerated biological aging is associated with elevated bladder cancer risk.

Creating area level indices of behaviours impacting cancer in Australia with a Bayesian generalised shared component model

This study develops a model-based index approach called the Generalised Shared Component Model (GSCM) by drawing on the large field of factor models. The proposed fully Bayesian approach accommodates heteroscedastic model error, multiple shared factors and flexible spatial priors. Moreover, unlike previous index approaches, our model provides indices with uncertainty. Focusing on unhealthy behaviors that increase the risk of cancer, the proposed GSCM is used to develop the Area Indices of Behaviors Impacting Cancer product — representing the first area level cancer risk factor index in Australia. This advancement aids in identifying communities with elevated cancer risk, facilitating targeted health interventions.

Various clinical manifestations of 223 patients with IgE deficiency in a tertiary hospital in China: A cross-sectional study.

High Immunoglobulin E(IgE) levels associated with hypersensitivity or parasitic infection were well established, but the clinical significance of ultra-low IgE was largely unknown. Previous studies indicated these patients have an elevated risk of cancer, but large-scale epidemiological studies on the prevalence and clinical manifestations of these ultra-low IgE patients are still lacking. A total of 62,997 patients who were admitted to the First Affiliated Hospital of Wenzhou Medical University and had IgE level tests from January 2010 to March 2020 were included. Patients with serum IgE levels < 2 IU/mL were defined to have ultra-low IgE. And the clinical characteristics of these patients were retrospectively analyzed based on electronic medical record system and follow-up. A total of 223 patients (223/62,997, 0.35%) had ultra-low IgE were documented in 62,997 patients who had IgE tests. Among the clinical manifestations of these 223 ultra-low IgE patients, infection ranked first (125/223, 56.05%), following allergic diseases (51/223, 22.87%), hematological disorders (37/223, 16.59%), tumor (27/223, 12.11%) and autoimmune diseases (23/223, 10.31%). To the best of our knowledge, we first reported that the prevalence and clinical characteristics of 223 ultra-low IgE patients in China. The most common comorbidities were infection, allergic diseases, hematological disorders, tumor and autoimmune diseases.

Renal cell carcinoma and risk of second primary cancer: A Danish nationwide cohort study.

To examine the risk of second primary cancer in patients with incident renal cell carcinoma (RCC). We identified all patients diagnosed with incident RCC during 1995-2019, using population-based Danish medical registries. Patients were followed from the date of RCC diagnosis until any second primary cancer diagnosis, death, emigration, or December 31, 2019, whichever came first. We computed the absolute risk, standardized incidence ratio (SIR), and excess absolute risk of second primary cancer, with 95% confidence intervals (CIs), among patients with RCC compared to the general population. The absolute 1- and 20-year risks of any second primary cancer were 2.8% and 17.8%, respectively. Within 1 year after RCC diagnosis, we detected 20 excess cancer cases per 1000 person-years (PY) (SIR, 2.3; 95% CI: 2.1-2.6). Moreover, we detected an additional four excess cancer cases per 1000 PY during 1 to <5 years of follow-up (SIR, 1.3; 95% CI: 1.2-1.4), and 6 per 1000 PY beyond 5 years of follow-up (SIR, 1.4; 95% CI: 1.3-1.5). The sustained elevated cancer risk beyond 1 year of follow-up was mainly attributed to excess risk of lung and bladder cancer. The risk of second primary cancer was higher in 2006-2019 than in 1995-2005, but only during the first year of follow-up. Patients with incident RCC have a sustained 40% elevated long-term risk of second primary cancer, compared with the general population. This increased risk is mainly attributed to lung and bladder cancer.

Implementing fragmentomics into real world screening interventions to evaluate clinical utility among individuals with elevated risk for lung cancer (FIRSTLUNG) L301.

TPS11189 Background: To optimize the impact of lung cancer screening at the healthcare system level, additional tools are needed to increase the benefits of screening. While low-dose computed tomography (LDCT) has been shown to improve lung cancer detection and reduce mortality, it is not without its risks, such as radiation exposure, false-positive results, and unnecessary interventions often leading to complications. The additional complexity of lung cancer screening is the subpar adherence to LDCT for eligible individuals, which undermines the benefits of screening. Therefore, there is a need for alternative non-invasive methodologies that exploit our understanding of the biology of cancer pathogenesis. This clinical utility study aims to observe how a non–invasive blood-based test impacts physician behavior and LDCT utilization. Methods: FIRSTLUNG 301 (NCT06145750) is a prospective, cluster randomized controlled trial (RCT) to observe the impact of the DELFI Lung cancer screening test on lung cancer screening utilization in primary care practices. Enrolled practices must meet the eligibility criteria of having a minimum of 50 actively engaged individuals in the practice eligible for lung cancer screening per the 2021 USPSTF criteria. These practices will be randomized 1:1:2 to Arm A1 (control), Arm A2 (control), or Arm B (intervention). Arm A practices will be randomized 1:1 into two groups (A1:A2) to observe the standard of care for lung cancer screening. Practices in A1 will be observed; practices in A2 will receive standard education on lung cancer screening for CME credit. Randomizing within Arms A1 and A2 aims to delineate the impact standard lung cancer screening education may have on utilization. Arm B (intervention) practices will receive education and have access to order the blood-based test for screen-eligible individuals that remained unscreened. The primary study endpoint is the proportion of practice-identified lung cancer screen-eligible individuals receiving a screening CT order and scan during the study period in the entirety of Arm A (control) versus Arm B (intervention). This RCT aims to understand the utilization and impact on lung cancer screening uptake after the DELFI blood-based test intended to inform clinical guidelines and policies focused on improving patient care and health outcomes. Progress: The study was initiated on October 31, 2023, with practice randomization. As of February 2024, the study is open for enrollment with an estimated primary study completion date of December 2025. Clinical trial information: NCT06145750 .

Novel Cancer Prevention Strategies in Individuals With Hereditary Cancer Syndromes: Focus on BRCA1, BRCA2, and Lynch Syndrome.

Germline pathogenic variants (PVs) in the BRCA1 and BRCA2 genes confer elevated risks of breast, ovarian, and other cancers. Lynch syndrome (LS) is associated with increased risks of multiple cancer types including colorectal and uterine cancers. Current cancer risk mitigation strategies have focused on pharmacologic risk reduction, enhanced surveillance, and preventive surgeries. While these approaches can be effective, they stand to be improved on because of either limited efficacy or undesirable impact on quality of life. The current review summarizes ongoing investigational efforts in cancer risk prevention strategies for patients with germline PVs in BRCA1, BRCA2, or LS-associated genes. These efforts span radiation, surgery, and pharmacology including vaccine strategies. Understanding the molecular events involved in the premalignant to malignant transformation in high-risk individuals may ultimately contribute significantly to novel prevention strategies.

Feasibility of universal breast cancer risk assessment in a diverse, publicly insured obstetrician gynecology clinic.

e13759 Background: Breast cancer is the most diagnosed cancer among women in the United States. Established breast cancer risk assessment (BCRA) tools can estimate a woman’s lifetime risk and inform the need for enhanced breast screening which can improve cancer-associated morbidity and mortality. Currently, critical disparities exist both in breast cancer prognosis and screening uptake. We aimed to evaluate the feasibility of routine BCRA in a diverse, publicly insured obstetrician gynecology clinic. Methods: All patients presenting to the obstetrician gynecology clinic were offered a BCRA using the Tyrer Cuzick (TC) risk model. Patients completed paper surveys and the information was input into the TC model to generate lifetime risk estimates. Printed evidence-based management guidelines were reviewed with and provided to those at ≥ 20% lifetime breast cancer risk and shared with the patient’s provider. Results: Between June 2023 and February 2024, 300 patients were approached and 208 (69.3%) completed the survey. One hundred seven (51.4%) survey respondents were presenting for obstetrical care and 101 (48.6%) for gynecologic care. Respondents had a median age of 33 years (IQR: 12). Ninety-six (46.2%) responding patients self-identified as Hispanic, 45 (21.6%) as Black, 25 (12.0%) as Asian, 28 (13.5%) as Non-Hispanic White, and 14 (6.7%) did not identify in these categories. One hundred eighty-nine (90.9%) survey respondents were publicly-insured. Ten (4.8%) patients were assisted by an interpreter. Overall, 12 (5.8%) patients had an elevated lifetime breast of breast cancer, defined as ≥ 20% based on the TC model (6 (50.0%) among obstetrical patients and 6 (50.0%) among gynecology patients). All patients at elevated risk were referred to a genetics clinic for counseling on options for enhanced breast surveillance. Conclusions: As leaders in women’s cancer care, gynecologic oncologists can lead and support programs to identify those women at highest risk for cancer, especially among historically underserved populations. Our feasibility study demonstrated that 69.3% of patients were willing to complete a BRCA and this tool identified 5.8% of patients to have a significantly elevated lifetime breast cancer risk. Providers should consider incorporating such tools in gynecologic oncology and obstetrical/gynecology clinics.

Skin cancer risk behaviors in sexual minority men: A mixed methods approach.

Sexual minority men experience disproportionately elevated rates of skin cancers, likely driven by excess ultraviolet radiation exposure-namely through tanning behaviors. However, limited integrated theoretical models exist to explain sexual minority men's elevated skin cancer risk. The aim of the current study is to further test and refine an integrated theory of skin cancer risk behaviors among sexual minority men by incorporating minority stress into the integrated health behavior model of tanning. The study employed a parallel mixed methods design, with a Phase 1 qualitative stage (N = 30) and a Phase 2 quantitative stage (Model 1: N = 320; Model 2: N = 319). In both phases, participants were sexual minority men, equally stratified as those with versus without recent tanning exposure and were recruited from across the United States. Qualitative and quantitative data supported the overall integrated model, with some quantitative paths varying depending on the tanning behavior outcome. Overall, appearance-related motives to tan and beliefs that tanning regulates affect emerged as the most consistent proximal predictors. Minority stress significantly predicted holding more positive attitudes toward tanning as an effective affect regulation strategy. The results from this mixed methods study support the inclusion of minority stressors into the adapted integrative health behavior model of tanning. Replication within prospective designs would strengthen the evidence for this model, which may be helpful in guiding future skin cancer prevention programs tailored to sexual minority men. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Linking periodontitis with 20 cancers, emphasis on oropharyngeal cancer: a Mendelian randomization analysis

While associations between periodontitis and an elevated risk of cancer have been suggested, the results of existing observational studies have been inconsistent, also leaving room for further investigation into the underlying mechanisms. This study was designed to delve into the possible causal link between periodontitis and 20 standard cancers while concurrently identifying potential mediators. We initiated a Mendelian randomization analysis that drew from either publicly accessible or personally obtained genome-wide association study (GWAS) datasets. The inverse variance weighting (IVW) method served as our primary tool for analysis. To ensure the strength and consistency of our results, we implemented additional strategies, including weighted median, weighted mode, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO), bolstered by funnel plots. Our analysis unveiled an elevated risk of head and neck cancer concomitant with periodontitis (p = 0.041, OR 0.999, 95% CI 0.999–1.000), specifically a heightened risk of oropharyngeal cancer (p = 0.022, OR 0.999, 95% CI 0.999–1.000). As a result of probing into potential mediators, Fusobacterium nucleatum emerged as a likely intermediary in the promoting effect of periodontitis on oropharyngeal cancer (p = 0.021, OR 0.999, 95% CI 0.998–1.000). Inversely, basal cell carcinoma and endometrial cancer demonstrated an association with an increased incidence of periodontitis (basal cell carcinoma: p = 0.020, OR 0.987, 95% CI 0.976–0.998; endometrial cancer: p = 0.027, OR 0.984, 95% CI 0.970–0.998). However, periodontitis exerted no significant causal impact on the 19 other common cancers or the three subtypes of head and neck cancer. To conclude, our results support the theory that periodontitis contributes to an enhanced risk of head and neck cancer, particularly oropharyngeal cancer, with Fusobacterium nucleatum functioning as a potential intermediary.

Rapid, portable and visualizing nitrite detection enabled by a rationally designed meso-aminoindole substituted pyronine-based fluorescent probe

Nitrite (NO2−) widely exists in our daily diet, and its excessive consumption can lead to detrimental effects on the human central nervous system and an elevated risk of cancer. The fluorescence probe method for the determination of nitrite has developed rapidly due to its simplicity, rapidity and sensitivity. Despite establishing various nitrite sensing platforms to ensure the safety of foods and drinking water, the simultaneous achievement of rapid, specific, affordable, visualizing, and on-site nitrite detection remains challenging. Here, we designed a novel fluorescent probe by using Rhodamine 800 as the fluorescent skeleton and 5-aminoindole as the specific reaction group to solve this problem. The probe shows a maximal fluorescence emission at 602 nm, thereby avoiding background emission interference when applied to food samples. Moreover, this unique probe exhibited excellent sensing capabilities for detecting nitrite. These included: a rapid response time within 3 min, a noticeable color change that the naked eye can observe, a low detection limit of 13.8 nM, and a remarkable selectivity and specificity to nitrite. Besides that, the probe can detect nitrite quantitatively in barreled drinking water, ham sausage, and pickles samples, with good recoveries ranging from 89.0 % to 105.8 %. More importantly, based on the probe fixation and signal processing technology, a portable and smart sensing platform was fabricated and made convenient and rapid analysis the content of NO2− in real samples possible. The results obtained in this work provide a new strategy for the design of high-performance nitrite probes and feasible technology for portable, rapid and visual detection of nitrite, and this probe holds the potential as a practical tool for alleviating concern regarding nitrite levels.

Association between Metabolic-Dysfunction-Associated Steatotic Liver Disease and Hepatic Cancer: Current Concepts and Future Challenges.

Background: This study systematically reviewed the association between metabolic-dysfunction-associated steatotic liver disease (MASLD) and the development of hepatic cancer. Previous research has highlighted MASLD as a predisposing condition. Aim: To collect recent global data on the relationship between MASLD and hepatic cancer. Methods: A systematic review was conducted, which included an analysis of studies on the relationship between MASLD and the incidence of hepatic cancers, focusing on the role of fibrosis and MASLD severity as predictors of cancer risk. Following standard methodological frameworks for the assessment of longitudinal studies, the review gathered information on fibrosis scores, hepatocellular carcinoma (HCC) incidence, and other types of hepatic neoplasms. Results: A total of 522 studies were initially identified, of which 6 studies were appropriate for the review. They collectively revealed that the stage of fibrosis in MASLD is a significant independent predictor of mortality and liver-related events, with higher fibrosis stages correlating with greater risk. Longitudinal data showed that increases in FIB-4 scores were linked to a higher risk of developing HCC and cirrhosis. MASLD was also associated with an increased risk of non-hepatic cancers such as colorectal cancer in males and breast cancer in females. The severity of MASLD was found to be a modifiable risk factor for biliary tract cancer (BTC), with the risk further amplified by diabetes. Moreover, lifestyle factors and comorbidities, such as smoking and diabetes, were identified as modifiers of cancer risk in MASLD patients. Conclusions: The systematic review identified the association between MASLD and an elevated risk of hepatic cancer, establishing a clear link between the severity of liver fibrosis and the incidence of HCC and other hepatic neoplasms. This supports the need for screening for hepatic cancer in patients with MASLD, particularly in the presence of advanced fibrosis or other risk-modifying factors.

Causal relationship between thyroid dysfunction and ovarian cancer: a two-sample Mendelian randomization study

PurposeObservational studies and clinical validation have suggested a link between thyroid dysfunction and an elevated ovarian cancer (OC) risk. However, whether this association indicates a cause-and-effect relationship remains uncertain. We aimed to investigate the plausible causal impact of thyroid dysfunction on OC through a Mendelian randomization (MR) study.MethodsGenome-wide association study (GWAS) data for thyrotropin (TSH), free thyroxine (FT4), hypothyroidism, and hyperthyroidism were obtained as exposures and those for OC (N = 199,741) were selected as outcomes. Inverse variance-weighted method was used as the main estimation method. A series of sensitivity analyses, including Cochran’s Q test, MR-Egger intercept analysis, forest plot scatter plot, and leave-one-out test, was conducted to assess the robustness of the estimates.ResultsGenetic prediction of hyperthyroidism was associated with a potential increase in OC risk (odds ratio = 1.094, 95% confidence interval: 1.029–1.164, p = 0.004). However, no evidence of causal effects of hypothyroidism, TSH, and FT4 on OC or reverse causality was detected. Sensitivity analyses demonstrated consistent and reliable results, with no significant estimates of heterogeneity or pleiotropy.ConclusionsThis study employed MR to establish a correlation between hyperthyroidism and OC risk. By genetically predicting OC risk in patients with hyperthyroidism, our research suggests new insights for early prevention and intervention of OC.

Occurrence, efficiency of treatment processes, source apportionment and human health risk assessment of pharmaceuticals and xenoestrogen compounds in tap water from some Ghanaian communities

The occurrence of pharmaceuticals and xenoestrogen compounds (PXCs) in drinking water presents a dire human health risk challenge. The problem stems from the high anthropogenic pollution load on source water and the inefficiencies of the conventional water treatment plants in treating PXCs. This study assessed the PXCs levels and the consequential health risks of exposure to tap water from selected Ghanaian communities as well as that of raw water samples from the respective treatment plants. Thus the PXCs treatment efficiency of two drinking water treatment plants in the metropolises studied was also assessed. The study also conducted source apportionment of the PXCs in the tap water. Twenty six (26) tap and raw water samples from communities in the Cape Coast and Sekondi-Takoradi metropolises were extracted using SPE cartridges and analysed for PXCs using Ultra-fast-HPLC-UV instrument. Elevated levels of PXCs up to 24.79 and 22.02 μg/L were respectively recorded in raw and tap water samples from the metropolises. Consequently, elevated non-cancer health risk (HI > 1) to residential adults were found for tap water samples from Cape Coast metropolis and also for some samples from Sekondi-Takoradi metropolis. Again, elevated cumulative oral cancer risks >10−5 and dermal cancer risk up to 4 × 10−5 were recorded. The source apportionment revealed three significant sources of PXCs in tap water samples studied. The results revealed the inefficiency of the treatment plants in removing PXCs from the raw water during treatments. The situation thus requires urgent attention to ameliorate it, safeguarding public health. It is recommended that the conventional water treatment process employed be augmented with advanced treatment technologies to improve their efficacy in PXCs treatment.

Oral and non-oral lichen planus show genetic heterogeneity and differential risk for autoimmune disease and oral cancer

Lichen planus (LP) is a T-cell-mediated inflammatory disease affecting squamous epithelia in many parts of the body, most often the skin and oral mucosa. Cutaneous LP is usually transient and oral LP (OLP) is most often chronic, so we performed a large-scale genetic and epidemiological study of LP to address whether the oral and non-oral subgroups have shared or distinct underlying pathologies and their overlap with autoimmune disease. Using lifelong records covering diagnoses, procedures, and clinic identity from 473,580 individuals in the FinnGen study, genome-wide association analyses were conducted on carefully constructed subcategories of OLP (n= 3,323) and non-oral LP (n= 4,356) and on the combined group. We identified 15 genome-wide significant associations in FinnGen and an additional 12 when meta-analyzed with UKBB (27 independent associations at 25 distinct genomic locations), most of which are shared between oral and non-oral LP. Many associations coincide with known autoimmune disease loci, consistent with the epidemiologic enrichment of LP with hypothyroidism and other autoimmune diseases. Notably, a third of the FinnGen associations demonstrate significant differences between OLP and non-OLP. We also observed a 13.6-fold risk for tongue cancer and an elevated risk for other oral cancers in OLP, in agreement with earlier reports that connect LP with higher cancer incidence. In addition to a large-scale dissection of LP genetics and comorbidities, our study demonstrates the use of comprehensive, multidimensional health registry data to address outstanding clinical questions and reveal underlying biological mechanisms in common but understudied diseases.

Prevalence of Cardiovascular and Cancer Risk Factors Among Rheumatoid Arthritis Patients Prescribed JAK Inhibitors and Tumor Necrosis Factor Inhibitors: A Cross-Sectional Study.

The study was to determine the prevalence of baseline risk factors for cardiovascular outcomes and cancer among commercially-insured patients with rheumatoid arthritis (RA) during their first dispensed treatment for either tumor necrosis factor inhibitors (TNFi) or JAK inhibitors (JAKi). Patients with RA from August 16, 2019 to March 31, 2022 were identified in the Merative MarketScan Commercial and Medicare databases. The first date that a TNFi or JAKi was dispensed was the index date, and baseline risk factors were assessed among patients continuously eligible for 12 months before the index date. Patients who had the following were stratified into an elevated risk category: age ≥65 years, smoking, or a history of a major adverse cardiovascular event, venous thromboembolism, or cancer. The prevalence of modifiable risk factors was also reported: hypertension, hyperlipidemia, obesity, and diabetes. The crude prevalence and prevalence difference (PD) were reported. A total of 12,673 patients (TNFi [n = 7,748; 61%] and JAKi [n = 4,925; 39%]) met inclusion criteria. The prevalence of elevated risk was the same for all patients using TNFi (n = 2,051; 26%) and JAKi (n = 1,262; 26%). Compared with patients having low risk, patients with an elevated risk also had a higher prevalence of at least one primary modifiable risk factor for both patients using JAKi (79% vs 58%; PD 21%, 95% confidence interval [CI] 18%-24%) and TNFi (81% vs 60%; PD 21%, 95% CI 19%-23%). In recent years, JAKi and TNFi were used in similar proportions to treat RA among commercially-insured patients at elevated cardiovascular and cancer risk. Because uncontrolled disease, modifiable comorbidities, and treatment with JAKi are associated with these adverse events, future studies evaluating how practice patterns may be affected by the emergence of safety data will be of value.

Polycystic ovary syndrome and endometrial cancer risk: results from a nationwide cohort study.

Most previous studies found an elevated risk of endometrial cancer among women with polycystic ovary syndrome (PCOS). However, these had highly varying methods for ascertainment of PCOS diagnoses and limitations such as few exposed women and short follow-up. In this cohort study, we investigated the association between PCOS and endometrial cancer among women born in Denmark between January 1, 1940, and December 31, 1993 (n=1 719 121). Data in this study, including PCOS and endometrial cancer diagnoses and covariates, were derived from nationwide registers. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% CIs. A total of 7862 endometrial cancer cases were identified during 23.7years of follow-up (IQR, 37.7-61.9). We found an increased risk of endometrial cancer among women with PCOS compared with women without PCOS (HR = 3.02; 95% CI, 2.03-4.49). The risk was increased for premenopausal women (HR = 5.82; 95% CI, 3.64-9.30), whereas no marked association was seen for postmenopausal women. However, for postmenopausal women, results were limited by few cases and young age at the end of follow-up. Mounting evidence of an increased risk for endometrial cancer among women with PCOS reinforces the need for prevention and early detection. This article is part of a Special Collection on Gynecological Cancers.

Porphyromonas gingivalis, a bridge between oral health and immune evasion in gastric cancer.

Porphyromonas gingivalis (P. gingivalis) is a gram-negative oral pathogen associated with chronic periodontitis. Previous studies have linked poor oral health and periodontitis with oral cancer. Severe cases of periodontal disease can result in advanced periodontitis, leading to tissue degradation, tooth loss, and may also correlate with higher gastric cancer (GC) risk. In fact, tooth loss is associated with an elevated risk of cancer. However, the clinical evidence for this association remains inconclusive. Periodontitis is also characterized by chronic inflammation and upregulation of members of the Programmed Death 1/PD1 Ligand 1 (PD1/PDL1) axis that leads to an immunosuppressive state. Given that chronic inflammation and immunosuppression are conditions that facilitate cancer progression and carcinogenesis, we hypothesize that oral P. gingivalis and/or its virulence factors serve as a mechanistic link between oral health and gastric carcinogenesis/GC progression. We also discuss the potential impact of P. gingivalis' virulence factors (gingipains, lipopolysaccharide (LPS), and fimbriae) on inflammation and the response to immune checkpoint inhibitors in GC which are part of the current standard of care for advanced stage patients.

Surveillance for metachronous cancers after endoscopic resection of esophageal squamous cell carcinoma.

The literature pertaining to surveillance following treatment for esophageal squamous cell carcinoma (SCC) was reviewed and summarized, encompassing the current status and future perspectives. Analysis of the standardized mortality and incidence ratios for these cancers indicates an elevated risk of cancer in the oral cavity, pharynx, larynx, and lungs among patients with esophageal SCC compared to the general population. To enhance the efficacy of surveillance for these metachronous cancers, risk stratification is needed. Various factors, including multiple Lugol-voiding lesions, multiple foci of dilated vascular areas, young age, and high mean corpuscular volume, have been identified as predictors of metachronous SCCs. Current practice involves stratifying the risk of metachronous esophageal and head/neck SCCs based on the presence of multiple Lugol-voiding lesions. Endoscopic surveillance, scheduled 6-12 months post-endoscopic resection, has demonstrated effectiveness, with over 90% of metachronous esophageal SCCs treatable through minimally invasive modalities. Narrow-band imaging emerges as the preferred surveillance method for esophageal and head/neck SCC based on comparative studies of various imaging techniques. Innovative approaches, such as artificial intelligence-assisted detection systems and radiofrequency ablation of high-risk background mucosa, may improve outcomes in patients following endoscopic resection.

Maternal residential exposure to solvents from industrial sources during pregnancy and childhood cancer risk in California

BackgroundMaternal solvent exposure has been suspected to increase offspring cancer risk. The study aimed to evaluate the associations between maternal residential exposure to solvents from industrial pollution during pregnancy and childhood cancer. MethodsThe present study included 15,744 cancer cases (aged 0–19 years at diagnosis) identified from California Cancer Registry and 283,141 controls randomly selected from California Birth Registry (20:1 frequency-matched by birth year: 1998–2016). We examined industrial releases of tetrachloroethylene and 1,1,1-trichloroethane within 3 km of the birth address, while we used a 5 km buffer for carbon disulfide. We calculated the total exposure from all linked Toxic Release Inventory sites during each index pregnancy and assigned “ever/never” and “high/low exposed/unexposed” exposure, using median values. We performed quadratic decay models to estimate cancer risks associated with maternal solvent exposure in pregnancy. Results1,1,1-Trichloroethane was associated with rhabdomyosarcoma (adjusted Odds Ratio (aOR): 1.96; 95% Confidence Interval (CI): 1.16, 3.32) in the “ever exposed” group. Ever exposure to carbon disulfide was associated with increased risks of medulloblastoma (OR = 1.85, 95% CI 1.01, 3.40) and ependymoma (OR = 1.63, 95% CI 0.97, 2.74). ConclusionsOverall, our findings suggested maternal residential exposure to solvents from industrial sources might be associated with elevated childhood cancer risks.

Abstract PO4-11-08: Risk of second malignancies in breast cancer patients. A population-based retrospective cohort study between 2010-2020

Abstract Introduction: Breast cancer survivors live longer due to early detection programs and therapeutic advances. Staging and molecular classification are important for prognosis and treatment. At the same time these patients are at increased risk for second primary cancers. Comprehensive evaluation of second cancer risk among patients treated in recent decade with early detection and prevention programs of other tumors lacking. This study aims to identify, characterize and associate breast cancers with second primary malignancies based on different variables. Methods: We identified 3487 females with a first primary breast cancer between 2010 and 2020 in medical records at University Hospital of A Coruña in Spain. Over a median follow-up of 8 years, one hundred patients (2,9%) develop second cancer. According National Cancer Institute, second primary tumor (SPT) was defined as an invasive primary cancer after a first primary cancer. In our case a breast carcinoma. Second cancer risk was evaluated for all cancers (excluding ipsilateral breast carcinoma) which were diagnosed at least 12 months after primary breast tumor. We analyzed breast cancer subtype, family history and pathogenic genetic variants, tobacco use and second primary tumor type. Results: Several clinical characteristics were evaluated, including breast cancer stage, histological type and subtype. The incidence of breast cancer and SPT was increased with age with peaks in the 60’s and 70’s, respectively. Only 13% had SPT between 40-49 years. Approximately 10 women a year, in our study, developed second cancer. 52% of SPT patients had cancer family history. Pathogenic variant study was carried in 25% of women with SPT, 46% of them no mutation were found, but in 17% was detected a germline BRCA1 deleterious variant. Other pathogenic variants were founded: 4% in BRCA2, and 33% in others genes (CHEK2, MSH2, MSH6, PMS2, CDH1, FANC1 y SMAD4) Regards tobacco use, active smokers were 13% and 12% of women had been smoking years ago. Of these 13 active smokers, 10 develop lung cancer (77%) an 5 of former smokers (42%). Luminal subtype was the most common breast cancer (33% Luminal A, 34% Luminal B Her2 negative, 10% Luminal B Her2 positive, 4% Her2-enriched, 10% Triple negative and 3% carcinoma in situ with estrogen and progesterone expression) and stage I and II were most frequent (80%). The most usual second primary neoplasms were lung, colorectal and pancreatic carcinoma (21%, 17% and 7% respectively), and only 2% contralateral breast cancer, with an average of approximately 4 years between breast cancer and the SPT. In 11% of patients were found more than 2 tumors. At the time of the analysis, 73% of these patients are free of disease. In SPT study population few recurrences were described, 2 relapses of breast cancer and 9 of SPT. The median between breast cancer diagnosis and the SPT diagnosis was 54 months [0,7 – 129]. The median to relapse of breast cancer was 73 months [68 – 77]. The median between SPT diagnosis and relapse was 39,25 months [1 - 134]. STP recurrences were observed in colorectal and lung cancer, mainly. Data on recurrences and mutations were not significative. Conclusion: In our breast cancer population the incidence of second primary tumors is around 3% over a 10 – year period. The diagnosis of the SPT arises several years after breast cancer and generally has a worse prognosis. Elevated risks of second cancer among breast cancer survivors treated in recent decade suggests that heightened surveillance is warranted and continued efforts to reduce second cancers are needed. It is mandatory make an effort and focusing in recommendations and advise about tobacco consumption, healthy lifestyle and adherence to Pap test and stool test in survivors. Citation Format: Guadalupe Rama, Maria-Eva Perez-Lopez, Silvia Antolin Novoa, Cristina Reboredo, Beatriz Alonso, Sofia Silva Diaz, Begoña Graña, Lourdes Calvo, Tomas Garcia-Caballero. Risk of second malignancies in breast cancer patients. A population-based retrospective cohort study between 2010-2020 [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-11-08.